METHOD OF SELECTING CONCENTRATOR NETWORK CONNECTIONS

L'invention concerne un procédé de sélection de concentrateurs de connexions réseau pour un ensemble donné de M ≥ 1 chemins de communication utilisables par un dispositif communicant, chaque interface respective dudit dispositif communicant étant connectée à un chemin respectif, ledit procédé comprenant les étapes suivantes : a) identification d'un ensemble (P1,P2,...,PN) de N ≥ 1 concentrateurs situés dans au moins un réseau auquel le dispositif communicant est connecté, chaque concentrateur permettant d'agréger des connexions exploitant une pluralité de chemins susceptibles d'être utilisés par le dispositif communicant ; b) obtention de la valeur d'au moins un paramètre de Qualité de Service QoS(i,j), pour au moins un chemin i, où i = et pour des concentrateurs Pj joignables à partir du dispositif communicant via ledit chemin i ; et c) sélection, pour au moins le chemin i, d'un concentrateur sur la base desdites valeurs de Qualité de Service obtenues. Application au protocole MPTCP (Multi-Path ...

Manual apparatus e.g. manual electric sucker, for capturing e.g. mosquitoes in home, has propeller permitting suction of flying insects, and driven by electric motor operating with battery or using manual mechanism

L'invention concerne un petit appareil permettant l'aspiration et la capture de petits insectes volants incommodants ou nuisibles, tels que mouches ou moustiques. L'aspiration est assurée par une hélice mue par un moteur électrique ou mécaniquement. Cet appareil permet une capture rapide des insectes sans attendre que ceux-ci pénètrent dans un piège ou se posent sur un ruban collant.

PROCESS OF COMBUSTION FOR THE PREPARATION OF LICOVO4

Separador para ceramica que permite la extraccion del separador mediante un tomador vertical plano y cuña, donde sobre una de sus cuatro aletas que componen la cruceta, se dispone un medio en forma de cuña, donde dicho medio es perpendicular a las aletas laterales.

Separador para cerámica que permite la extracción del separador mediante un tomador vertical plano, y cuña, donde sobre una de sus cuatro aletas que componen la cruceta, se dispone un medio en forma de cuña, donde dicho medio es perpendicular a las aletas laterales.

电话用户线路的线路端接设备

... 在用于发送和接收窄带低频话音信号和宽带高频数据信号的线路端接设备中，模拟接收电路在采用一用于数据信号-补偿的平衡滤波器(49)的情况下被分成两条用于话音和数据的单独的模拟电路(32、33)。在发送方向上由数字滤波器(43、45)进行数字部分中的话音和数据信号电路的分离。本发明适用于应用xDSL-方法，例如非对称用户线路中的话音和数据信号的分离。 ...

METHOD AND DEVICE FOR DETECTING METAL ITEMS

用于粒化设备的喷洒头

... 本发明公开了一种用于粒化设备的喷洒头，其包括一个狭缝式喷嘴(22)，该喷嘴有一个带有中心轴线(38)的椭圆形横截面的圆柱形控制主体(36)。所述控制主体(36)大致被置中地介于喷嘴通道(26)的底表面(28)以及顶表面(30)之间，并且可绕其中心轴线(38)枢轴式转动。在控制主体(36)的下方以及上方形成喷嘴狭缝(42，44)，狭缝高度可通过使椭圆形一圆柱形控制主体(36)绕其中心轴线(38)进行枢轴式转动来调节。 ...

LIGHT SOURCE, AND OPTICAL COHERENCE TOMOGRAPHY MODULE

A swept wavelength light source is provided, the light source includes a semiconductor gain device operable to provide amplification, an optical retarding device, the retarding device having a block of material, a beam path with a well-defined beam path length being defined for light within the block of material produced by the gain device, a wavelength selector, and the gain device, the retarding device and wavelength selector being mutually arranged on the base so that a resonator is established for light portions emitted by the gain device and selected by wavelength selector; this does not exclude the presence of further elements contributing to the resonator, such as additional mirrors (including resonator end mirrors), lenses, polarization selective elements, other passive optical components, etc.; wherein the beam path in the retarding device is a part of a beam path of the resonator. 1. A light source , comprising:an optical module casing with at least one optical feedthrough and a plurality of electrical feedthroughs,a semiconductor gain device operable to provide light amplification;a wavelength selector; andlight re-directors;the gain device, the light re-directors and the wavelength selector being mutually arranged in the optical module casing so that a multimode resonator is established for light portions emitted by the gain device and selected by the wavelength selector;wherein the resonator is an external cavity laser resonator;and wherein one end reflector of the resonator is partially transmitting and wherein light transmitted through this one end reflector is at least partially directed to exit through the optical feedthrough.2. The light source according to claim 1 , further comprising a common thermoelectric cooler in thermal contact with at least the semiconductor gain device and the wavelength selector.3. The light source according to claim 1 , wherein the resonator comprises an optical retarding device claim 1 , the retarding device comprising ...

Anti-Tenascin-C A2 Antibodies and Methods of Use

The invention provides antibodies against the A2 domain of tenascin-C and methods of using the same. 1. An isolated antibody that specifically binds to the A2 domain of tenascin A2 (TNC A2) , wherein the antibody comprises three heavy chain complementarity determining regions (HCDRs) HCDR1 , HCDR2 , HCDR3 and three light chain CDRs (LCDRs) LCDR1 , LCDR2 , LCDR3 , having the amino acid sequences as follows:(a) a heavy chain CDR1 selected from the group of SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 7;(b) a heavy chain CDR2 selected from the group of SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO:21, SEQ ID NO: 23, and SEQ ID NO: 25;(c) a heavy chain CDR3 of SEQ ID NO: 27;(d) a light chain CDR1 selected from the group of SEQ ID NO: 29, SEQ ID NO: 31, and SEQ ID NO: 33;(e) a light chain CDR2 selected from the group of SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, and SEQ ID NO: 45; and(f) a light chain CDR3 of SEQ ID NO:47,wherein said antibody does not comprise the combination of a heavy chain CDR1 (HCDR1) selected from the group of SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, and a heavy chain CDR2 (HCDR2) selected from the group of SEQ ID NO: 9, SEQ ID NO: 15, and SEQ ID NO: 21, and the heavy chain CDR3 (HCDR3) of SEQ ID NO: 27, and the light chain CDR1 (LCDR1) of SEQ ID NO: 29, and the light chain CDR2 (LCDR2) of SEQ ID NO: 35, and the light chain CDR3 (LCDR3) of SEQ ID NO:47.2. The antibody of claim 1 , which is a monoclonal antibody.3. The antibody of claim 1 , which is a human claim 1 , a humanized claim 1 , or a chimeric antibody.4. The antibody of claim 1 , which is an antibody fragment that binds to the A2 domain of TNC A2.5. The antibody of claim 1 , wherein said antibody binds to human TNC A2 with a KD value lower than about 1 μM.6. An isolated antibody that specifically binds to the A2 domain of tenascin A2 (TNC A2) claim 1 , wherein the antibody comprises a heavy chain variable ...

SPEECH RECOGNITION USER INTERFACE

Speech recognition techniques are disclosed herein. In one embodiment, a novice mode is available such that when the user is unfamiliar with the speech recognition system, a voice user interface (VUI) may be provided to guide them. The VUI may display one or more speech commands that are presently available. The VUI may also provide feedback to train the user. After the user becomes more familiar with speech recognition, the user may enter speech commands without the aid of the novice mode. In this “experienced mode,” the VUI need not be displayed. Therefore, the user interface is not cluttered. 1. A method of controlling an electronic device , comprising:receiving a voice input that indicates speech recognition is requested;determining whether the voice input is for a first mode or a second mode of speech recognition;displaying a voice user interface on a display screen of the electronic device in response to determining that the voice input is for the first mode, the voice user interface shows one or more speech commands that are currently available;providing speech recognition training through the voice user interface when in the first mode; andcontrolling the electronic device based on a command in the voice input in response to determining that the voice input is for the second mode.2. The method of claim 1 , wherein the determining whether the voice input is for a first mode or a second mode of speech recognition includes:recognizing a presently valid command in the voice input; anddetermining that the voice input is for the second mode in response to recognizing the presently valid command.3. The method of claim 1 , wherein the providing speech recognition training through the voice user interface includes providing visual feedback while the user is speaking.4. The method of claim 1 , further comprising:automatically determining that a user is done using speech recognition, the automatically determining is performed while in the first mode; andremoving the ...

ANTI-FAP ANTIBODIES AND METHODS OF USE

The invention provides antibodies against Fibroblast Activation Protein (FAP) and methods of using the same. 1. An antibody that specifically binds to Fibroblast Activation Protein (FAP) , wherein said antibody is glycoengineered to have increased effector function.2. An antibody that specifically binds to Fibroblast Activation Protein (FAP) , wherein said antibody comprises at least one heavy or light chain complementarity determining region (CDR) selected from the group of SEQ ID NO: 3 , SEQ ID NO: 5 , SEQ ID NO: 7 , SEQ ID NO: 9 , SEQ ID NO: 11 , SEQ ID NO: 13 , SEQ ID NO: 15 , SEQ ID NO: 17 , SEQ ID NO: 19 , SEQ ID NO:21 , SEQ ID NO: 23 , SEQ ID NO: 25 , SEQ ID NO: 27 , SEQ ID NO: 29 , SEQ ID NO: 31 , SEQ ID NO: 33 , SEQ ID NO: 35 , SEQ ID NO: 37 , SEQ ID NO: 39 , SEQ ID NO: 41 , SEQ ID NO: 43 , SEQ ID NO: 45 , SEQ ID NO: 47 , SEQ ID NO: 49 , SEQ ID NO: 51 , SEQ ID NO: 53 , SEQ ID NO: 55 , SEQ ID NO: 57 , SEQ ID NO: 59 , SEQ ID NO: 61 , SEQ ID NO: 63 , SEQ ID NO: 65 , SEQ ID NO: 67 , SEQ ID NO: 69 , SEQ ID NO: 71 , SEQ ID NO: 73 , SEQ ID NO: 75 , SEQ ID NO: 77 , SEQ ID NO: 79 , SEQ ID NO: 81 , SEQ ID NO: 83 , SEQ ID NO: 85 , SEQ ID NO: 87 , SEQ ID NO: 89 , SEQ ID NO: 91 , SEQ ID NO: 93 , SEQ ID NO: 95 , SEQ ID NO: 97 , SEQ ID NO: 99 , SEQ ID NO: 101 , SEQ ID NO: 103 , SEQ ID NO: 105 , SEQ ID NO: 107 , SEQ ID NO: 109 , SEQ ID NO: 111 , SEQ ID NO: 113 , SEQ ID NO: 115 , SEQ ID NO: 117 , SEQ ID NO: 119 , SEQ ID NO: 121 , SEQ ID NO: 123 , SEQ ID NO: 125 , SEQ ID NO: 127 , SEQ ID NO: 129 , SEQ ID NO: 131 , SEQ ID NO: 133 , SEQ ID NO: 135 , SEQ ID NO: 137 , SEQ ID NO: 139 , SEQ ID NO: 141 , SEQ ID NO: 143 , SEQ ID NO: 145 , SEQ ID NO: 147 , SEQ ID NO: 149 , SEQ ID NO: 151 , SEQ ID NO: 153 , SEQ ID NO: 155 , SEQ ID NO: 157 , SEQ ID NO: 159 , SEQ ID NO: 161 , SEQ ID NO: 163 , SEQ ID NO: 165 , SEQ ID NO: 167 , SEQ ID NO: 169 , SEQ ID NO: 171 , SEQ ID NO: 173 , SEQ ID NO: 175 , and SEQ ID NO: 177 , or a combination thereof.3. The antibody of claim 2 , wherein said ...

Fuel Injection System For an Internal Combustion Engine

The invention relates to a high-pressure fuel pump comprising a drive shaft supported by bearings, and fuel flows through the bearings in a forced manner in such a way that the mechanical and thermal load-carrying capacity of the bearings, and thus the entire high-pressure fuel pump, is significantly increased.

Antibodies Against Human Angiopoietin 2

The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. An antibody which binds specifically to human angiopoietin-2 (ANG-2) , wherein said antibody comprises:(A) a heavy chain variable domain which comprises a CDR3 region of SEQ ID NO: 33, a CDR2 region of SEQ ID NO: 34 and a CDR1 region of SEQ ID NO: 35;(B) a light chain variable domain which comprises a CDR3 region of SEQ ID NO: 36, a CDR2 region of SEQ ID NO: 37 and a CDR1 region of SEQ ID NO: 38.2. An antibody according to claim 1 , comprising a heavy chain variable domain of SEQ ID NO: 39; and a light chain variable domain of SEQ ID NO: 40.3. An antibody according to wherein said antibody does not bind to human Angiopoietin 1 (ANG-1).4. An antibody according to wherein said antibody is of the human IgG4 subclass or the human IgG1 subclass.5. A pharmaceutical composition comprising an antibody according to or a fragment thereof.6. A method of treating a disease or disorder in a patient comprising administering an antibody according to to a patient in need of such treatment.7. A method according to wherein said disease or disorder is cancer.8. A method according to wherein said disease or disorder is a vascular disease.9. A method according to wherein said disease or disorder is a retinopathy.10. A method for preventing metastasis in a patient suffering from primary cancer comprising administering an antibody according to to a patient in need of such preventative treatment. This application is a continuation of U.S. application Ser. No. 12/635,825, filed Dec. 11, 2009, now pending, which claims the benefit of European Patent Application No. 08021835.7, filed Dec. 16, 2008. The entire contents of the above-identified applications are hereby incorporated by reference.The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), ...

Antibodies Against Human Angiopoietin 2

The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A nucleic acid encoding a heavy chain of an antibody which binds specifically to human angiopoietin-2 (ANG-2) , wherein the variable domain of said heavy chain comprises a CDR3 region selected from the group consisting of: SEQ ID NO: 1 , SEQ ID NO: 9 , SEQ ID NO: 17 , SEQ ID NO: 25 , SEQ ID NO: 33 , SEQ ID NO: 41 , and SEQ ID NO: 49.2. A nucleic acid according to wherein said variable domain of said heavy chain further comprisesa CDR2 region selected from the group consisting of:SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42, and SEQ ID NO: 50;and a CDR1 region selected from the group consisting of: SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 19, SEQ ID NO: 27, SEQ ID NO: 35, SEQ ID NO: 43, and SEQ ID NO: 51.3. A nucleic acid according to wherein said variable domain of said heavy chain is selected from the group consisting of: SEQ ID NO: 7 claim 1 , SEQ ID NO: 15 claim 1 , SEQ ID NO: 23 claim 1 , SEQ ID NO: 31 claim 1 , SEQ ID NO: 39 claim 1 , SEQ ID NO: 47 claim 1 , and SEQ ID NO: 55.4. A nucleic acid according to wherein said variable domain of said heavy chain comprises a CDR3 region of SEQ ID NO: 1 claim 1 , a CDR2 region of SEQ ID NO: 2 claim 1 , and a CDR1 region of SEQ ID NO: 3.5. A nucleic acid according to wherein said variable domain of said heavy chain is of SEQ ID NO: 7.6. A nucleic acid according to wherein said variable domain of said heavy chain comprises a CDR3 region of SEQ ID NO: 17 claim 1 , a CDR2 region of SEQ ID NO: 18 claim 1 , and a CDR1 region of SEQ ID NO: 19.7. A nucleic acid according to wherein said variable domain of said heavy chain is of SEQ ID NO: 23.8. An expression vector characterized in comprising a nucleic acid according to for the expression of said antibody in a prokaryotic or eukaryotic ...

BISPECIFIC ANTI-EGFR/ANTI-IGF-1R ANTIBODIES

The present invention relates to bispecific antibodies against EGFR and against IGF-1R, methods for their production, pharmaceutical compositions containing said antibodies, and methods of treatment using the antibodies. 1. A bispecific antibody binding to EGFR and IGF-1R comprising a first antigen-binding site that binds to EGFR and a second antigen-binding site that binds to IGF-1R , characterized in thati) said antigen-binding sites are each a pair of an antibody heavy chain variable domain and an antibody light chain variable domain;ii) said first antigen-binding site comprises in the heavy chain variable domain a CDR3 region of SEQ ID NO: 1, a CDR2 region of SEQ ID NO: 2, and a CDR1 region of SEQ ID NO:3, and in the light chain variable domain a CDR3 region of SEQ ID NO: 4, a CDR2 region of SEQ ID NO:5, and a CDR1 region of SEQ ID NO:6; and 'or said second antigen-binding site comprises in the heavy chain variable domain a CDR3 region of SEQ ID NO: 17, a CDR2 region of SEQ ID NO: 18, and a CDR1 region of SEQ ID NO:19, and in the light chain variable domain a CDR3 region of SEQ ID NO: 20, a CDR2 region of SEQ ID NO:21, and a CDR1 region of SEQ ID NO:22.', 'iii) said second antigen-binding site comprises in the heavy chain variable domain a CDR3 region of SEQ ID NO: 11, a CDR2 region of SEQ ID NO: 12, and a CDR1 region of SEQ ID NO:13, and in the light chain variable domain a CDR3 region of SEQ ID NO: 14, a CDR2 region of SEQ ID NO:15, and a CDR1 region of SEQ ID NO:16;'}2. The bispecific antibody according to claim 1 , characterized in thatsaid second antigen-binding site comprises in the heavy chain variable domain a CDR3 region of SEQ ID NO: 11, a CDR2 region of SEQ ID NO: 12, and a CDR1 region of SEQ ID NO:13, and in the light chain variable domain a CDR3 region of SEQ ID NO: 14, a CDR2 region of SEQ ID NO:15, and a CDR1 region of SEQ ID NO:16.3. The bispecific antibody according to claim 1 , characterized in thatsaid second antigen-binding site comprises in ...

PERSISTENT HANDLES FOR INTERFACE GUIDES

A computing system translates a world space position of a hand of a human target to a screen space position of a user interface and locks the hand to a handle of the user interface if world space parameters of the hand overcome a grab threshold of the handle. When the hand is locked to the handle, the computing system translates a world space position of the hand to a screen space handle position that is constrained along one or more interface guides. The hand is unlocked from the handle at a release position of the handle if world space parameters of the hand overcome a release threshold of the handle. The handle is retained at the release position after the hand is unlocked from the handle. 1. A computing system , comprising:a logic subsystem; translate a world space position of a hand of a human target to a screen space position of a user interface;', 'lock the hand to a handle of the user interface if world space parameters of the hand overcome a grab threshold of the handle;', 'when the hand is locked to the handle, translate a world space position of the hand to a screen space handle position that is constrained along one or more interface guides;', 'unlock the hand from the handle at a release position of the handle if world space parameters of the hand overcome a release threshold of the handle; and', 'retain the handle at the release position after the hand is unlocked from the handle., 'a data holding subsystem holding instructions executable by the logic subsystem to2. The computing system of claim where the world space parameters of the hand overcome the grab threshold of the handle if the hand is closed by the human target.3. The computing system of claim 1 , where the world space parameters of the hand overcome the grab threshold of the handle if a screen space position of the hand is within a threshold distance of the handle for a duration threshold.4. The computing system of claim 1 , where the world space parameters of the hand overcome the grab ...

Method for cylinder equalization in a multi-cylinder internal combustion engine

A method is provided for equalizing the cylinders of a multi-cylinder internal combustion engine. The internal combustion engine is configured as a reciprocating engine having direct injection and spark ignition. A fuel mass is injected in a cylinder-specific manner, and a cylinder-specific air mass and a cylinder-specific ignition time are each adjustable. An injection amount is equalized, then a charge is equalized and then a mean combustion pressure is equalized.

Combination therapy of a type II anti-CD20 antibody with a proteasome inhibitor

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a proteasome inhibitor for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and a proteasome inhibitor. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and a proteasome inhibitor. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and a proteasome inhibitor. 1. A composition comprising a type II anti-CD20 antibody and a proteasome inhibitor.2. A composition according to claim 1 , wherein said proteasome inhibitor has an IC50 of the anti-proteasome inhibitory activity of 5 μM or less.3. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.64. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.5. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).6. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.7. A composition according to claim 1 , wherein said proteasome inhibitor is selected from the group consisting of peptide aldehydes claim 1 , peptide boronates claim 1 , peptide epoxyketones claim 1 , and salinosporamide A.8. A composition according to claim 1 , wherein said proteasome inhibitor is bortezomib.9. A composition according to claim 1 , further comprising one or more additional other cytotoxic claim 1 , chemotherapeutic or anti-cancer agents claim 1 , ...

BIVALENT, BISPECIFIC ANTIBODIES

The present invention relates to nucleic acids which encode the heavy chains and light chains of a novel domain exchanged, bivalent, bispecific antibody, and vectors comprising the same. 1. An isolated nucleic acid encoding the heavy chain of an antibody wherein the VH domain of said heavy chain is replaced by the VL domain of the corresponding light chain of said antibody.2. An isolated nucleic acid according to wherein said antibody is an anti-IGF-1R antibody.3. An isolated nucleic acid according to wherein said heavy chain is a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 10.4. An isolated nucleic acid encoding the light chain of an antibody wherein the VL domain of said light chain is replaced by the VH domain of the corresponding heavy chain of said antibody.5. An isolated nucleic acid according to wherein said antibody is an anti-IGF-1 R antibody.6. An isolated nucleic acid according to wherein the said light chain is a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 11.7. An isolated nucleic acid according to wherein the constant heavy chain domain CH3 domain is replaced by the constant heavy chain domain CH1 of said heavy chain.8. An isolated nucleic acid according to wherein the constant heavy chain domain CH3 is replaced by the constant light chain domain CL of said antibody.9. An isolated nucleic acid according to wherein the constant heavy chain domain CH3 is altered so that an amino acid residue is replaced with an amino acid residue having a larger side chain volume.10. An isolated nucleic acid according to claim 9 , wherein the amino acid residue having a larger side chain volume is selected from the group consisting of arginine (R) claim 9 , phenylalanine (F) claim 9 , tyrosine (Y) claim 9 , tryptophan (W).11. An isolated nucleic acid according to claim 10 , wherein said heavy chain contains an T366W substitution.12. An isolated ...

Monovalent Antigen Binding Proteins

The present invention relates to monovalent antigen binding proteins with a CH1-CL domain exchange, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A monovalent antigen binding protein comprisinga) a modified heavy chain of an antibody which specifically binds to an antigen, wherein the VH domain is replaced by the VL domain of said antibody; andb) a modified heavy chain of said antibody, wherein the CH1 domain is replaced by the CL domain of said antibody.2. The monovalent antigen binding protein according to claim 1 , comprisingthe CH3 domain of the modified heavy chain of the antibody of a) and the CH3 domain of the modified heavy chain of the antibody of b) each meet at an interface which comprises an original interface between the antibody CH3 domains;wherein said interface is altered to promote the formation of the monovalent antigen binding protein, wherein the alteration comprises:i) a CH3 domain of one heavy chain is altered,so that within the original interface the CH3 domain of one heavy chain that meets the original interface of the CH3 domain of the other heavy chain within the monovalent antigen binding protein,an amino acid residue is replaced with an amino acid residue having a larger side chain volume, thereby generating a protuberance within the interface of the CH3 domain of one heavy chain which is positionable in a cavity within the interface of the CH3 domain of the other heavy chainandii) the CH3 domain of the other heavy chain is altered,so that within the original interface of the second CH3 domain that meets the original interface of the first CH3 domain within the monovalent antigen binding protein,an amino acid residue is replaced with an amino acid residue having a smaller side chain volume, thereby generating a cavity within the interface of the second CH3 domain within which a protuberance within the interface of the first CH3 domain is positionable.3. The monovalent antigen ...

MUTANT INTERLEUKIN-2 POLYPEPTIDES

The present invention generally relates to mutant interleukin-2 polypeptides that exhibit reduced affinity to the α-subunit of the IL-2 receptor, for use as immunotherapeutic agents. In addition, the invention relates to immunoconjugates comprising said mutant IL-2 polypeptides, polynucleotide molecules encoding the mutant IL-2 polypeptides or immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant IL-2 polypeptides or immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof. 1. A mutant interleukin-2 (IL-2) polypeptide comprising at a first amino acid mutation that abolishes or reduces affinity of the mutant IL-2 polypeptide to the high-affinity IL-2 receptor and preserves affinity of the mutant IL-2 polypeptide to the intermediate-affinity IL-2 receptor , each compared to a wild-type IL-2 polypeptide , characterized in that said first amino acid mutation is at a position corresponding to residue 72 of human IL-2.2. The mutant interleukin-2 polypeptide of claim 1 , wherein said first amino acid mutation is an amino acid substitution claim 1 , selected from the group of L72G claim 1 , L72A claim 1 , L72S claim 1 , L72T claim 1 , L72Q claim 1 , L72E claim 1 , L72N claim 1 , L72D claim 1 , L72R claim 1 , and L72K.3. The mutant interleukin-2 polypeptide of or claim 1 , comprising a second amino acid mutation that abolishes or reduces affinity of the mutant IL-2 polypeptide to the high-affinity IL-2 receptor and preserves affinity of the mutant IL-2 polypeptide to the intermediate-affinity IL-2 receptor claim 1 , each compared to a wild-type IL-2 polypeptide.4. The mutant interleukin-2 polypeptide of claim 3 , wherein said second amino acid mutation is at a position selected from the positions corresponding to residue 35 claim 3 , 38 claim 3 , 42 claim 3 , 43 claim 3 , and 45 of human IL-2.5. The mutant interleukin-2 polypeptide of or claim 3 , ...

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH AN ANTI-BCL-2 ACTIVE AGENT

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and an anti-Bcl-2 active agent. 1. A composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent.2. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.63. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.4. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).5. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.6. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is selected from the group consisting of Oblimersen claim 1 , SPC-2996 claim 1 , RTA-402 claim 1 , Gossypol claim 1 , AT-101 claim 1 , Obatoclax mesylate claim 1 , A-371191 claim 1 , A-385358 claim 1 , A-438744 claim 1 , ABT-737 claim 1 , AT-101 claim 1 , BL-11 claim 1 , BL-193 claim 1 , GX-15-003 claim 1 , 2-Methoxyantimycin A claim 1 , HA-14-1 claim 1 , KF-67544 claim 1 , Purpurogallin claim 1 , TP-TW-37 claim 1 , YC-137 and Z-24.7. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is ...

NOVEL IMMUNOCONJUGATES

The present invention generally relates to antigen-specific immunoconjugates for selectively delivering effector moieties that influence cellular activity. More specifically, the invention provides novel immunoconjugates comprising a first antigen binding moiety, an Fc domain and a single effector moiety. In addition, the present invention relates to polynucleotides encoding such immunoconjugates, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the immunoconjugates of the invention, and to methods of using these immunoconjugates in the treatment of disease. 1. An immunoconjugate comprising a first antigen binding moiety , an Fc domain consisting of two subunits , and an effector moiety , wherein not more than one effector moiety is present.2. The immunoconjugate of claim 1 , wherein said Fc domain comprises a modification promoting heterodimerization of two non-identical polypeptide chains.3. The immunoconjugate of claim 2 , wherein said modification is a knob-into-hole modification claim 2 , comprising a knob modification in one of the subunits of the Fc domain and a hole modification in the other one of the two subunits of the Fc domain.4. The immunoconjugate of claim 1 , wherein said Fc domain is engineered to have altered binding to an Fc receptor and/or altered effector function.5. The immunoconjugate of claim 1 , wherein the effector moiety is a cytokine.6. The immunoconjugate of claim 5 , wherein said cytokine is IL-2.7. An isolated polynucleotide encoding the immunoconjugate of claim for a fragment thereof.8. An expression vector comprising the isolated polynucleotide of .9. A host cell comprising the expression vector of .10. A method of producing the immunoconjugate comprising a first antigen binding moiety claim 9 , an Fc domain consisting of two subunits claim 9 , and an effector moiety claim 9 , wherein not more than one effector moiety is present claim 9 , comprising culturing the host ...

UNDER VOLTAGE TOLERANT CLAMP

An apparatus comprises an integrated circuit (IC) comprising an external IC connection, an IC substrate connection, a voltage clamp circuit and an under voltage circuit. The voltage of the IC substrate connection is set to a first voltage when a voltage of the external connection of the IC is within a normal operating voltage range. The voltage clamp circuit is configured to clamp the voltage supply of one or more circuits internal to the IC to within a normal operating voltage range when the voltage of the external IC connection exceeds the normal operating voltage range. The under voltage circuit is communicatively coupled to the clamp circuit and configured to set the voltage of the substrate to a second voltage when the voltage at the external IC connection of the IC is less than zero volts. 1. An integrated circuit (IC) comprising:an external IC connection;an IC substrate connection, wherein a voltage of the IC substrate connection is set to a first voltage when a voltage of the external connection of the IC is within a normal operating voltage range;a voltage clamp circuit configured to clamp the voltage supply of one or more circuits internal to the IC to within a normal operating voltage range when the voltage of the external IC connection exceeds the normal operating voltage range; andan under voltage circuit communicatively coupled to the clamp circuit and configured to set the voltage of the substrate to a second voltage when the voltage at the external IC connection of the IC is less than zero volts.2. The IC of claim 1 , wherein the under voltage circuit is configured to set the voltage of the substrate to substantially the voltage at the external IC connection when the voltage at the external IC connection is less than zero volts.3. The IC of claim 2 , wherein the under voltage circuit is configured to set the voltage of the IC substrate connection to within a transistor threshold voltage of the voltage of the external IC connection when the voltage of ...

VOICE-BODY IDENTITY CORRELATION

A system and method are disclosed for tracking image and audio data over time to automatically identify a person based on a correlation of their voice with their body in a multi-user game or multimedia setting. 1. A method of identifying a correlation between a user and user voice , the method comprising the steps of:(a) receiving images of one or more users taken over a plurality of time periods;(b) receiving audio of voices for a plurality of time periods; and(c) correlating a voice identified in said step (b) to a user of the one or more users based on a plurality of samplings of determined positions of the user in different images and determined source locations of the voice at different times.2. The method recited in claim 1 , said step (c) comprising the step of a sampling of the plurality of samplings being formed by determining a location of the one or more users from examination of an image of the plurality of images and being formed by determining a location of the voice using an acoustic source localization technique.3. The method recited in claim 1 , said step (c) comprising the step of performing a first sampling of the plurality of samplings to obtain a confidence level in an association between the voice and the user claim 1 , a confidence level above a predefined threshold resulting in the voice and the user being associated together in memory.4. The method recited in claim 3 , said step (c) comprising the step of the confidence level going up in subsequent samplings of the plurality of samplings if the subsequent samplings decrease the number of possible users to whom the voice can belong to.5. The method recited in claim 4 , further comprising the step of unambiguously correlating the voice to a user upon eliminating all other users to whom the voice could belong to in the plurality of samplings.6. The method recited in claim 5 , further comprising the step of performing additional samplings in the plurality of samplings after the correlation ...

TRIVALENT, BISPECIFIC ANTIBODIES

The present invention relates to trivalent, bispecific antibodies, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof. 1. A trivalent , bispecific antibody comprisinga) a full length antibody that specifically binds to a first antigen wherein the full length antibody consists of two antibody heavy chains and two antibody light chains;b) a polypeptide consisting ofba) an antibody heavy chain variable domain (VH); orbb) an antibody heavy chain variable domain (VH) and an antibody constant domain 1 (CH1), wherein the N-terminus of the VH domain of the polypeptide is fused via a peptide connector to the C-terminus of one of the two heavy chains of the full length antibody;c) a polypeptide consisting ofca) an antibody light chain variable domain (VL), orcb) an antibody light chain variable domain (VL) and an antibody light chain constant domain (CL);wherein N-terminus of the VL domain of the polypeptide is fused via a peptide connector to the C-terminus of the other of the two heavy chains of the full length antibody;and wherein the antibody heavy chain variable domain (VH) of the polypeptide under b) and the antibody light chain variable domain (VL) of the polypeptide under c) together form an antigen-binding site specifically binding to a second antigen.2. The trivalent claim 1 , bispecific antibody according to claim 1 , whereinthe CH3 domain of one heavy chain and the CH3 domain of the other heavy chain each meet at an interface which comprises an alteration in the original interface between the antibody CH3 domains;wherein i) in the CH3 domain of one heavy chainan amino acid residue is replaced with an amino acid residue having a larger side chain volume, thereby generating a protuberance within the interface of the CH3 domain of one heavy chain which is positionable in a cavity within the interface of the CH3 domain of the other heavy chain and whereinii) in the CH3 domain of the other heavy chainan amino acid ...

COMPOUND GESTURE-SPEECH COMMANDS

A multimedia entertainment system combines both gestures and voice commands to provide an enhanced control scheme. A user's body position or motion may be recognized as a gesture, and may be used to provide context to recognize user generated sounds, such as speech input. Likewise, speech input may be recognized as a voice command, and may be used to provide context to recognize a body position or motion as a gesture. Weights may be assigned to the inputs to facilitate processing. When a gesture is recognized, a limited set of voice commands associated with the recognized gesture are loaded for use. Further, additional sets of voice commands may be structured in a hierarchical manner such that speaking a voice command from one set of voice commands leads to the system loading a next set of voice commands. 1. A method for controlling a computing system using a voice commands , comprising:accessing multiple depth images from a depth sensor system;recognizing a gesture from the multiple depth images;in response to recognizing a gesture, choosing a subset of a set of sound commands based on the recognized gesture, the set of sound commands includes multiple subsets, each subset is associated with one or more gestures and sound command recognition data for the respective subset;receiving sound input;recognizing a sound command from the chosen subset based on the sound input; andperforming an action in response to the recognized sound command.2. The method of claim 1 , wherein:the depth images include a two-dimensional pixel area of a captured scene, the pixels in the two-dimensional pixel area represent depth values of one or more objects in the scene captured by the depth sensor system.3. The method of claim 1 , further comprising:loading sound command recognition data for the chosen subset of sound commands.4. The method of claim 1 , wherein:the sound input is received from a microphone.5. The method of claim 1 , wherein:the recognizing includes attempting to match the ...

BISPECIFIC ANTIBODIES SPECIFIC FOR T-CELL ACTIVATING ANTIGENS AND A TUMOR ANTIGEN AND METHODS OF USE

The present invention relates to bispecific antibodies that specifically bind a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A bispecific antibody that specifically binds a T-cell activating antigen and a Tumor Antigen (TA) , comprising a first Fab fragment and a second Fab fragment , wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain.2. The bispecific antibody of claim 1 , wherein the first fragment comprises at least one antigen binding site specific for a Tumor Antigen; and the second Fab fragment comprises at least one antigen binding site specific for a T-cell activating antigen.3. The bispecific antibody of claim 1 , wherein the T-cell activating antigen is a CD3 T-Cell Co-Receptor (CD3) antigen.4. The bispecific antibody of claim 1 , wherein the N-terminus of the second Fab fragment is connected to the C-terminus of the first Fab fragment.5. The bispecific antibody of claim 1 , additionally comprising a third Fab fragment.6. The bispecific antibody of claim 5 , wherein the third Fab fragment comprises at least one antigen binding site specific for a Tumor Antigen.7. The bispecific antibody of claim 5 , wherein the third Fab fragment is connected to the first Fab fragment.8. The bispecific antibody of claim 7 , wherein the C-terminus of the third Fab fragment is connected to the N-terminus of the first Fab fragment.9. The bispecific antibody of claim 5 , wherein the third Fab fragment is connected to the second Fab fragment.10. The bispecific antibody of claim 9 , wherein the N- ...

Bispecific antigen binding molecules

The present invention generally relates to novel bispecific antigen binding molecules. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A bispecific antigen binding molecule , comprising a first Fab fragment which specifically binds to a first antigen , a second Fab fragment which specifically binds to a second antigen , and an Fc domain composed of a first and a second subunit capable of stable association; whereina) the bispecific antigen binding molecule provides monovalent binding to the first and/or the second antigen,b) the first Fab fragment, the second Fab fragment and the first Fc domain subunit are fused to each other, and 'provided that not the same replacement is made in the first and the second Fab fragment.', 'c) in the first and/or the second Fab fragment one of the following replacements is made: (i) the variable domains VL and VH are replaced by each other, (ii) the constant domains CL and CH1 are replaced by each other, or (iii) both the variable and constant domains VL-CL and VH-CH1 are replaced by each other,'}2. The bispecific antigen binding molecule of claim 1 , wherein the first Fab fragment is fused at its C-terminus to the N-terminus of the second Fab fragment claim 1 , which is in turn fused at its C-terminus to the N-terminus of the first Fc domain subunit.3. The bispecific antigen binding molecule of claim 2 , wherein the first Fab fragment is fused at the C-terminus of its heavy chain to the N-terminus of the heavy chain of the second Fab fragment claim 2 , which is in turn fused at the C-terminus of its heavy chain to the N-terminus of the first Fc domain subunit.4. The bispecific antigen binding ...

FC-FREE ANTIBODIES COMPRISING TWO FAB FRAGMENTS AND METHODS OF USE

The present invention relates to bispecific antibodies comprising at least two fab fragments, wherein the first Fab fragment comprises at least one antigen binding site specific for a first antigen; and the second Fab fragment comprises at least one antigen binding site specific for a second antigen, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody is devoid of a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A bispecific antibody comprising at least two fab fragments , wherein the first fab fragment comprises at least one antigen binding site specific for a first antigen; and the second fab fragment comprises at least one antigen binding site specific for a second antigen wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody is devoid of a Fc domain.2. The bispecific antibody of claim 1 , additionally comprising a third fab fragment.3. The bispecific antibody of claim 2 , wherein the third fab fragment comprises at least one antigen binding site specific for the first or second antigen.4. The bispecific antibody of claim 2 , wherein the third fab fragment comprises at least one antigen binding site specific for the first antigen.5. The bispecific antibody of claim 2 , wherein the third fab fragment is connected to the first fab fragment.6. The bispecific antibody of claim 5 , wherein the C-terminus of the third Fab fragment is connected to the N-terminus of the first Fab fragment.7. The bispecific antibody of claim 2 , wherein the third Fab fragment is connected to the second Fab fragment.8. The bispecific antibody of claim 7 , wherein the N-terminus of the third Fab fragment is connected to the C-terminus of the first Fab fragment.9. The bispecific antibody of or claim 7 , wherein the fab fragments ...

Method and Apparatus for Interchanging Data, and Network

A method for interchanging data between two devices in a network which utilizes a communication protocol with an interface based on the OPC-UA standard to interchange the data, wherein the communication protocol comprises an interface based on the stream reservation protocol standard or an interface based on the multiple stream registration protocol standard in accordance with IEEE standard 802.1Qat, such that the data is interchangeable between the two devices using both interfaces in a prescribed period of time. 17.-. (canceled)8. A method for interchanging data between two devices of a network , the method comprising:utilizing a communication protocol with an interface in accordance with an Object Linking and Embedding for Process Control United Architecture (OPC-UA) standard for interchanging the data; andinterchanging the data between the two devices via both interfaces in a prescribed period of time, the communication protocol including an interface in accordance with one of a Stream Reservation Protocol (SRP) standard and a Multiple Stream Registration Protocol (MSRP) standard in with IEEE standard 802.1 Qat.9. The method as claimed in claim 8 , wherein the communication protocol is configured in accordance with an Open Systems Interconnection Reference Model as a multilayer protocol;wherein each layer is assigned an interface; and{'b': 1', '2', '2, 'wherein, for a first type of data a layer sequence in accordance with the OPC-UA standard is executed (W) and for a second type of data, during execution, deviation (W) from the layer sequence occurs in accordance with the OPC-UA standard (W), such that one of an SRP or MSRP interface is used and the second type of data is interchanged between the two devices in the prescribed period of time.'}10. The method as claimed in claim 9 , wherein the communication protocol comprises an application layer claim 9 , an OPC-UA interface claim 9 , a TCP/IP interface claim 9 , an Ethernet interface and a physical interface ...

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A T cell activating bispecific antigen binding molecule comprising a first and a second antigen binding moiety , one of which is a Fab molecule capable of specific binding to an activating T cell antigen and the other one of which is a Fab molecule capable of specific binding to a target cell antigen , and an Fc domain composed of a first and a second subunit capable of stable association; (a) a single chain Fab molecule wherein the Fab light chain and the Fab heavy chain are connected by a peptide linker, or', '(b) a crossover Fab molecule wherein either the variable or the constant regions of the Fab light chain and the Fab heavy chain are exchanged., 'wherein the first antigen binding moiety is'}2. The T cell activating bispecific antigen binding molecule of claim 1 , comprising not more than one antigen binding moiety capable of specific binding to an activating T cell antigen.3. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first and the second antigen binding moiety are fused to each other claim 1 , optionally via a peptide linker.4. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the second antigen binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the Fab heavy chain of the first antigen binding moiety.5. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first antigen binding moiety is fused at ...

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A T cell activating bispecific antigen binding molecule comprising a first and a second single chain Fv (scFv) molecule fused to each other , wherein the first scFv molecule is capable of specific binding to a target cell antigen and the second scFv molecule is capable of specific binding to an activating T cell antigen;characterized in that the T cell activating bispecific antigen binding molecule further comprises an Fc domain composed of a first and a second subunit capable of stable association.2. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first scFv molecule is fused at the C-terminus to the N-terminus of the second scFv molecule claim 1 , and the second scFv molecule is fused at the C-terminus to the N-terminus of the first or the second subunit of the Fc domain.3. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the second scFv molecule is fused at the C-terminus to the N-terminus of the first scFv molecule claim 1 , and the first scFv molecule is fused at the C-terminus to the N-terminus of the first or the second subunit of the Fc domain.4. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the Fc domain is an IgG claim 1 , specifically an IgGor IgG claim 1 , Fc domain.5. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the Fc domain is a human Fc domain.6. The T cell activating bispecific antigen ...

CHARGER DETECTION WITH PROPRIETARY CHARGER SUPPORT

Method and apparatus, among other things, are provided for detecting a charger type. In an example, a method to classify a potential charger coupled to a port of an electronic device can include detecting the potential charger coupled to a USB-compatible port of the electronic device, applying a pull-down current to first and second data lines of the USB-compatible port to provide a first test voltage on each of the first and second data lines, and executing a primary detection process of a USB Battery Charging 1.2 Compliance Plan if the first test voltage on each of the first and second data lines is not between a first threshold and a second threshold using the pull-down current. 1. A charger detection method configured to classify a potential charger coupled to a port of an electronic device , the charger detection method comprising:detecting the potential charger coupled to a USB-compatible port of the electronic device;applying a pull-down current to first and second data lines of the USB-compatible port to provide a first test voltage on each of the first and second data lines; andexecuting a primary detection process of a USB Battery Charging 1.2 Compliance Plan if the first test voltage on each of the first and second data lines is not between a first threshold and a second threshold.2. The charger detection method of claim 1 , including classifying the potential charger as a dedicated charging port (DCP) device if a first test voltage on each of the first and second data lines is between the first threshold and the second threshold using the pull-down current.3. The charger detection method of claim 1 , including claim 1 ,coupling a second test voltage to the first data line to provide a third voltage on the second data line; anddelaying a first delay interval.4. The charger detection method of claim 3 , including claim 3 ,detecting that a voltage on the second data line is outside a first test window after expiration of the first delay interval;coupling a ...

Two-Stage Swipe Gesture Recognition

Systems, methods and computer program products for facilitating the recognition of user air swipe gestures are disclosed. Such systems, methods and computer program products provide a two-stage gesture recognition approach that combines desirable aspects of object manipulation gestures and symbolic gestures in order to create an interaction that is both reliable and intuitive for users of a computing system. In a first position-based stage, the user moves the cursor into a swipe activation zone. Second, in a motion-based stage, the user swipes their hand from the activation zone past a swipe gate within a certain amount of time to complete the interaction. GUI feedback is provided following the first stage to let the user know that the swipe interaction is available, and after the second stage to let the user know that the swipe is completed. 1. A method for facilitating the recognition of air swipe gestures , the method executing on at least one processor of a computing device , comprising the steps of:(a) detecting the movement of a cursor, by a user, into a first activation zone within a graphical user interface screen of an application executing on the computing device;(b) starting a first countdown timer, upon detecting said cursor exiting said first activation zone;(c) determining whether said cursor has crossed a swipe gate before the expiration of said first countdown timer; (i) providing a first response to said user via said graphical user interface screen; said first response indicative that said application executing on the computing device has recognized an air swipe;', '(ii) starting a second countdown timer; and', '(iii) disabling a second activation zone within said graphical user interface screen until said second countdown timer has expired; and, '(d) when said determining step (c) is positive (iv) providing a second response to said user via said graphical user interface screen; said second response indicative that said application executing on ...

Adaptive Area Cursor

Described is a technology by which a user's cursor movement is assisted to help select elements of a user interface that may be otherwise difficult to target. An area cursor is provided that may intersect more than one element. If so, a computation result (e.g., a percentage) is computed for each intersected element that is based upon intersection with the cursor and a total size of the element; the largest percentage intersection is selected. The computation (e.g., intersected area divided by total element area) favors smaller elements as they have a smaller area in the denominator. Also described is changing the cursor size to help hit elements and/or based upon one or more criteria. Still further described is determining the total size of an element based upon weighting, in addition to or instead of the element's actual size. Weighting may be based upon one or more criteria. 1. In a computing environment , a method performed at least in part on at least one processor comprising:positioning a cursor among elements of a user interface based upon user-controlled cursor movement, and computing for each intersected element a computation result that is based upon a first size that corresponds to intersection of that element with the cursor and a second size that corresponds to a total size of that element to provide a plurality of computation results for the plurality of intersected elements, and', 'using the plurality of computation results to determine user selection intent with respect to which of the plurality of intersected elements to target., 'determining whether the cursor intersects a plurality of elements, and if so2. The method of wherein each element corresponds to a two-dimensional area and wherein the cursor is a two-dimensional area cursor claim 1 , and wherein the computation result for each element corresponds to a percentage value comprising an area of the element that intersects with the area cursor divided by a total area of the element.3. The ...

Method for Controlling an Electric Machine and Control Device

A method for controlling an electric machine or electric unit by actuating a component of the electric machine or unit using a predicate and by automatically examining the component in regard to the performance of the predicate to permit examination of an automated system for possible errors in a simply manner, wherein the predicate contains an expected value of a (physical) quantity of the component, and wherein in the examination of the component, a check is performed to determine whether the expected value actually arises when the predicate is performed such that erroneous situations can be detected by a runtime system without explicit programming being necessary therefor. 19.-. (canceled)10. A method for controlling an electric machine or electric unit , comprising the steps of:actuating a component of the electric machine or electric unit using a predicate in which a functional relationship is defined between a subject and the component, the predicate including an expected value of a quantity of the component;automatically examining the component to determine a performance of the predicate; andchecking during examination of the component to determine whether the expected value occurs when the predicate is performed;wherein the component includes a self-description including run-time information which is used as a reference for a quantity during the examination; andwherein a control signal for the electric machine or electric unit is obtained from a difference between the reference for the quantity and the expected value.11. The method as claimed in claim 10 , wherein in the examination claim 10 , the quantity of the component is measured and the resulting measured value is accordingly checked to determine whether it falls within an estimated range which is based on the expected value.12. The method as claimed in claim 10 , wherein the expected value is a relative value.13. The method as claimed in claim 11 , wherein the expected value is a relative value.14. ...

CONTENT SYSTEM WITH SECONDARY TOUCH CONTROLLER

A controller for a content presentation and interaction system which includes a primary content presentation device. The controller includes a tactile control input and a touch screen control input. The tactile control input is responsive to the inputs of a first user and communicatively coupled to the content presentation device. The controller a plurality of tactile input mechanisms and provides a first set of the plurality of control inputs manipulating content. The controller includes a touch screen control input responsive to the inputs of the first user and communicatively coupled to the content presentation device. The second controller is proximate the first controller and provides a second set of the plurality of control inputs. The second set of control inputs includes alternative inputs for at least some of the controls and additional inputs not available using the tactile input mechanisms. 1. A controller for a content presentation and interaction system including a primary content presentation device , comprising:a tactile control input responsive to the inputs of a first user and communicatively coupled to the content presentation device, including a plurality of tactile input mechanisms and providing a first set of control inputs manipulating content;a touch screen control input responsive to the inputs of the first user and communicatively coupled to the content presentation device, the screen proximate the tactile control input and providing a second set of control inputs, the second set of control inputs including alternative inputs for at least some of the first set of control inputs and additional inputs not available using the tactile input mechanisms.2. The controller of wherein the controller communicates with the content presentation device and the content presentation device communicates with an entertainment service via a network claim 1 , the service providing one or more elements of a secondary interface claim 1 , the secondary interface ...

Bispecific Anti ErbB1 / Anti cMet Antibodies

The present invention relates to bispecific antibodies against human ErbB-1 and against human c-Met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof. 1. A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met , wherein the bispecific antibody causes an increase in internalization of c-Met on OVCAR-8 cells of no more than 15% when measured after 2 hours of OVCAR-8 cell-antibody incubation as measured by a flow cytometry assay as compared to internalization of c-Met on OVCAR-8 cells in the absence of the bispecific antibody.2. The bispecific antibody according to wherein the antibody is a bivalent or trivalent bispecific antibody comprising one or two antigen-binding sites that specifically bind to human ErbB-1 and a third antigen-binding site that specifically binds to human c-Met.3. The antibody according to comprisinga) a full length antibody that specifically binds to ErbB-1 consisting of two antibody heavy chains and two antibody light chains; andb) one single chain Fab fragment that specifically binds to human c-Met,wherein the single chain Fab fragment under b) is fused to the full length antibody under a) via a peptide connector to the C- or N-terminus of the heavy or light chain of the full length antibody.4. A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met claim 2 , wherein 'the second antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 30, a CDR2H region with the amino acid sequence of, SEQ ID NO: 31, and a CDR1H region with the amino acid sequence of SEQ ID NO: 32, and in the light ...

ANTIBODIES AGAINST HUMAN ANGIOPOIETIN 2

The present invention relates to a method of treating a disease or disorder in a patient comprising administering, to a patient in need of such treatment, an antibody which binds specifically to human angiopoietin-2 (ANG-2), wherein said antibody comprises: 1. A method of treating a disease or disorder in a patient comprising administering , to a patient in need of such treatment , an antibody which binds specifically to human angiopoietin-2 (ANG-2) , wherein said antibody comprises:(A) a heavy chain variable domain which comprises a CDR3 region of SEQ ID NO: 1, a CDR2 region of SEQ ID NO: 2 and a CDR1 region of SEQ ID NO: 3;(B) a light chain variable domain which comprises a CDR3 region of SEQ ID NO: 4, a CDR2 region of SEQ ID NO: 5 and a CDR1 region of SEQ ID NO: 6.2. A method according to wherein said disease or disorder is cancer.3. A method according to wherein said disease or disorder is a vascular disease.4. A method according to wherein said heavy chain variable domain has the sequence of SEQ ID NO: 7 and said light chain variable domain has the sequence of SEQ ID NO: 8.5. A method for preventing metastasis in a patient suffering from primary cancer comprising administering claim 1 , to a patient in need of such preventative treatment claim 1 , an antibody which binds specifically to human angiopoietin-2 (ANG-2) claim 1 , wherein said antibody comprises:(A) a heavy chain variable domain which comprises a CDR3 region of SEQ ID NO: 1, a CDR2 region of SEQ ID NO: 2 and a CDR1 region of SEQ ID NO: 3;(B) a light chain variable domain which comprises a CDR3 region of SEQ ID NO: 4, a CDR2 region of SEQ ID NO: 5 and a CDR1 region of SEQ ID NO: 6.6. A method according to wherein said heavy chain variable domain has the sequence of SEQ ID NO: 7 and said light chain variable domain has the sequence of SEQ ID NO: 8. This application is a continuation application of U.S. application Ser. No. 13/358,813, which is a divisional application of U.S. application Ser. No. 12/ ...

INPUT COMMANDS

Input command techniques are described. In one or more implementations, a computing device processes one or more inputs that are received from one or more input sources to determine a command that corresponds to the one or more inputs. The command is exposed to one or more controls that are implemented as software that is executed on the computing device and that have subscribed to the command. 1. A method comprising:processing one or more inputs by a computing device that are received from one or more input sources to determine a command that corresponds to the one or more inputs; andexposing the command to one or more controls that are implemented as software that is executed on the computing device and that have subscribed to the command.2. A method as described in claim 1 , wherein the processing is configured to be performed for a plurality of different types of input sources.3. A method as described in claim 2 , wherein the exposing of the command is performed such that the command is not indicative of the type of input source used to provide the command.4. A method as described in claim 1 , wherein the processing is configured to be performed responsive to a determination that the one or more controls have subscribed to the command.5. A method as described in claim 1 , wherein the processing includes processing an output of a translation module that is configured to translate source-specific information of a corresponding said input source to an application-readable format.6. A method as described in claim 5 , wherein the translation module is implemented as one or more device drivers.7. A method as described in claim 1 , wherein the processing includes normalization of the one or more inputs to produce a lower-bandwidth representation of the one or more inputs.8. A method as described in claim 1 , wherein the processing includes conversion of input-specific data into the command such that the command includes command-specific data that is semantically ...

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH AN ANTI-VEGF ANTIBODY

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with an anti-VEGF antibody for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly antibody and an anti-VEGF antibody. 17-. (canceled)8. A composition comprising a humanized B-Ly1 antibody , wherein the antibody is afucosylated with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 , and bevacizumab or a B20 series antibody , for the treatment of cancer.9. A method of treatment of a patient suffering from cancer by administering an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 , in combination with an anti-VEGF antibody , to a patient in the need of such treatment.10. The method according to claim 9 , wherein said cancer is a CD20 expressing cancer.11. The method according to or claim 9 , wherein said CD20 expressing cancer is a B-Cell Non-Hodgkin's lymphoma (NHL).12. The method according to any one of to claim 9 , wherein said anti-CD20 antibody is a humanized B-Ly1 antibody.13. The method according to any one of to claim 9 , wherein said anti-VEGF antibody is bevacizumab claim 9 , a B20 series antibody or G6 series antibody.14. The method according to any one of to claim 9 , wherein said anti-CD20 antibody is a humanized B-Ly1 antibody and said anti-VEGF antibody is bevacizumab or a B20 series antibody.15. The method according to any one of to claim 9 , wherein one or more additional other cytotoxic claim 9 , chemotherapeutic or anti-cancer agent claim 9 , or compound or ionizing radiation that enhances the effects of such agent is administered. This application claims the benefit of European Patent Application No. 10173108.1, filed on Aug. 17, 2010, the disclosure of which is incorporated herein by reference in its entirety.The present invention is directed to the ...

COMBINATION THERAPY WITH TYPE I AND TYPE II ANTI-CD20 ANTIBODIES

The present invention is directed to a combination therapy involving a type I anti-CD20 antibody and a type II anti-CD20 antibody for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type I anti-CD20 antibody and a type II anti-CD20 antibody. Another aspect of the invention is a kit comprising a type I anti-CD20 antibody and a type II anti-CD20 antibody. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type I anti-CD20 antibody and a type II anti-CD20 antibody. 1. A composition comprising a type I anti-CD20 antibody and a type II anti-CD20 antibody.2. A composition according to wherein said type I anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC No. CCL-86) of said type I anti-CD20 antibody compared to rituximab of 0.8 to 1.2 claim 1 , and said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.6.3. A composition according to wherein said type I anti-CD20 antibody and said type II anti-CD20 antibody are each monoclonal antibodies.4. A composition according to wherein said type I anti-CD20 antibody is rituximab.5. A composition according to wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.6. A composition according to wherein said type I anti-CD20 antibody is rituximab and said type II anti-CD20 antibody is a humanized B-Ly1 antibody.7. A composition according to wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity.8. A composition according to wherein at least 40% or more of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.9. A composition according to wherein said type I anti-CD20 ...

Bispecific Anti ErbB2/Anti cMet Antibodies

The present invention relates to bispecific antibodies against human ErbB-2 and against human C-met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof. 1. A bispecific antibody that specifically binds to human ErbB-2 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-2 and a second antigen-binding site that specifically binds to human c-Met , wherein the bispecific antibody causes an increase in internalization of c-Met on OVCAR-8 cells of no more than 15% when measured after 1 hour of OVCAR-8 cell-antibody incubation as measured by a flow cytometry assay , as compared to internalization of c-Met on OVCAR-8 cells in the absence of antibody.2. The bispecific antibody according to wherein the antibody is a bivalent or trivalent bispecific antibody comprising one or two antigen-binding sites that specifically bind to human ErbB-2 and a third antigen-binding site that specifically binds to human c-Met.3. The antibody according to comprising:a) a full length antibody that specifically binds to ErbB-2 consisting of two antibody heavy chains and two antibody light chains; andb) one single chain Fab fragment that specifically binds to human c-Met,wherein the single chain Fab fragment under b) is fused to the full length antibody under a) via a peptide connector to the C- or N-terminus of the heavy or light chain of the full length antibody.4. A bispecific antibody that specifically binds to human ErbB-2 and human C-met comprising a first antigen-binding site that specifically binds to human ErbB-2 and a second antigen-binding site that specifically binds to human c-Met claim 2 , whereinthe first antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 15, a CDR2H region with the amino acid sequence of SEQ ID NO: 16, and a CDR1H region with the amino acid sequence of SEQ ID NO:17, and in the light chain variable ...

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH A mTOR INHIBITOR

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with a mTOR inhibitor for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and a mTOR inhibitor such as Temsirolimus or Everolimus. 1. A method of treatment of a patient suffering from cancer by administering an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less , in combination with a mTOR inhibitor.2. The method according to claim 1 , wherein the amount of fucose is between 40% and 60%.3. The method according to claim 1 , wherein the amount of fucose of is 50% or less.4. The method according to any one of claim 3 , wherein said cancer is a CD20 expressing cancer.5. The method according to claim 4 , wherein said CD20 expressing cancer is a B-Cell Non-Hodgkin's lymphoma (NHL).6. The method according to any one of to claim 4 , wherein said afucosylated anti-CD20 antibody is a type II anti-CD20 antibody.7. The method according to claim 6 , wherein said antibody is a humanized B-Ly1 antibody.8. The method according to claim 7 , wherein said mTOR inhibitor is rapamycin claim 7 , or a rapamycin analog or derivative.9. The method according to claim 7 , wherein said mTOR inhibitor is Temsirolimus or Everolimus.10. The method according to claim 7 , wherein one or more additional other cytotoxic claim 7 , chemotherapeutic or anti-cancer agents claim 7 , or compounds or ionizing radiation that enhance the effects of such agents are administered.11. A composition comprising an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less and a mTOR inhibitor for the treatment of cancer.12. The composition according to claim 11 , wherein said anti-afucosylated CD20 antibody is a humanized B-Ly1 antibody.13. A method of treatment of a patient suffering from cancer by administering an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less in ...

DETECTION OF A POSTTRANSLATIONALLY MODIFIED POLYPEPTIDE BY A BI-VALENT BINDING AGENT

A bi-valent binding agent having a first monovalent binder that binds to a polypeptide epitope of a target polypeptide, a second monovalent binder that binds to a posttranslational polypeptide modification on the target polypeptide and a linker. Further disclosed are methods for the detection of a posttranslationally modified target polypeptide, for making the disclosed bi-valent binding agent, and for use of the disclosed bi-valent binding agent in histological staining procedures. 1. A bi-valent binding agent for binding a posttranslationally modified target polypeptide consisting of:{'sup': −3', '−4, 'a first monovalent binder which binds to a polypeptide epitope of a target polypeptide and having a Kdiss in the range of 5×10/sec to 10/sec;'}{'sup': −3', '−4, 'a second monovalent binder which binds to a posttranslational polypeptide modification of the target polypeptide and having a Kdiss in the range of 5×10/sec to 10/sec; and'}{'sup': '−5', 'a linker linking the first monovalent binder to the second monovalent binder, the bi-valent binding agent having a Kdiss of 3×10/sec or less.'}2. The bi-valent binding agent of claim 1 , wherein one of the first and the second monovalent binders comprises one of a single chain antibody claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment of a monoclonal antibody.3. The bi-valent binding agent of claim 1 , wherein the first and second monovalent binders are derived from monoclonal antibodies and are one of Fab-fragments claim 1 , Fab′-fragments claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment.4. The bi-valent binding agent of claim 1 , wherein said bi-valent binding agent has a Kdiss of 10/sec or less.5. The bi-valent binding agent of claim 1 , wherein the linker has a length of 6 to 100 nm.6. The bi-valent binding agent of claim 5 , wherein the linker further comprises a label.7. The bi-valent binding agent of claim 6 , wherein the label is a digoxigenin molecule.8. The bi-valent binding agent of claim 5 , wherein ...

COMBINATION THERAPY

The present invention is directed to the combination therapy of an afucosylated antibody specifically binding to a tumor-antigen with human IL-15 for the treatment of cancer. 1. Anti-CD20 antibody in combination with human IL-15 for use in treatment of cancer.2. Anti-CD20 antibody according to characterized in that said CD20 antibody is an afucosylated antibody with an amount of fucose of 60% or less claim 1 , and said cancer is a CD20 expressing cancer.3. Anti-CD20 antibody according to any one of claim 2 , characterized in that said anti-CD20 antibody is a humanized B-Ly1 antibody.4. Anti-CD20 antibody according to any one of to claim 2 , characterized in that said anti-CD20 antibody is obinutuzumab.5. Anti-CD20 antibody according to any one of to claim 2 , characterized in that said the cancer is leukemia.6. Anti-CD20 antibody according to any one of to claim 2 , characterized in that said the cancer is chronic lymphocytic leukemia.7. Anti-CD20 antibody according to any one of to claim 2 , characterized in that the Anti-CD20 antibody is an afucosylated antibody which shows an increased ADCC.8. Anti-CD20 antibody according to any one of to claim 2 , characterized in that one or more additional other cytotoxic claim 2 , chemotherapeutic or anti-cancer agents claim 2 , or compounds or ionizing radiation that enhance the effects of such agents are administered.9. A method for the treatment of cancer claim 2 , comprising administering to a patient in need of such treatment an anti-CD20 antibody and a human IL-15.10. The method of claim 9 , comprising co-administering the anti-CD20 antibody and the human IL-15.11. The method of or claim 9 , wherein the anti-CD20 antibody and the human IL-15 are administered sequentially or simultaneously.12. The method according to claim 9 , wherein the CD20 antibody is an afucosylated antibody with an amount of fucose of 60% or less claim 9 , and said cancer is a CD20 expressing cancer.13. The method according to claim 9 , wherein the ...

HANDLES INTERACTIONS FOR HUMAN-COMPUTER INTERFACE

A system is disclosed for providing on-screen graphical handles to control interaction between a user and on-screen objects. A handle defines what actions a user may perform on the object, such as for example scrolling through a textual or graphical navigation menu. Affordances are provided to guide the user through the process of interacting with a handle. 1. In a system comprising a computing environment coupled to a capture device for capturing user position and providing a human-computer interface , the system further comprising a display displaying an image a method of facilitating user interaction with an area of the graphical image for the human-computer interface , comprising:(a) generating a handle tied to the area of the graphical image;(b) detecting engagement by the user with the handle generated in said step (a);(c) receiving an indication of gesture by the user relating to the area tied to the handle engaged in said step (b); and(d) performing an action on the area of the graphical image in response to said step (c).2. The method of claim 1 , said step (a) comprising the step of displaying the handle on the area of the graphical image.3. The method of claim 1 , said step (a) comprising the step of displaying the handle adjacent the area of the graphical image.4. The method of claim 1 , said step (a) comprising the step of integrating the handle as part of the area of the graphical image so that no separate handle is displayed.5. The method of claim 1 , said step (a) comprising the step of displaying the handle as a circular graphical object of two or three dimensions.6. The method of claim 1 , said step (a) comprising the step of displaying the handle as a graphical object and further comprising the step (e) of changing an appearance of the handle on the display from said step (a) to said step (b) and from said step (b) to said step (c).7. The method of claim 1 , said step (b) of detecting engagement by the user with the handle facilitated by ...

RECOMBINANT FC-FUSION PROTEIN OF THE FIFTH FIBRONECTIN TYPE III DOMAIN OF DCC

The present invention relates to DCC-fusion proteins, nucleic acid molecules encoding the DCC-fusion proteins, as well as methods for their production and their use in treatment of cancer such as colorectal cancer, NSCLC and metastatic breast cancer. The present invention also relates to methods of treating cancer such as colorectal cancer, NSCLC and metastatic breast cancer by administering DCC-fusion proteins. 111-. (canceled)12. A DCC-fusion protein comprising the amino acid sequence of SEQ ID NO: 213. A DCC-fusion protein comprising the amino acid sequence of SEQ ID NO: 3.14. A nucleic acid molecule encoding the DCC-fusion protein according to .15. A nucleic acid molecule encoding the DCC-fusion protein according to .16. The nucleic acid molecule according to which comprises the nucleotide sequence of SEQ ID NO: 1.17. The nucleic acid molecule according to which comprises the (new) nucleotide sequence of SEQ ID NO: 1.18. A vector containing the nucleic acid according capable of expressing said nucleic acid in a eukaryotic host cell.19. A vector containing the nucleic acid according capable of expressing said nucleic acid in a eukaryotic host cell.20. A host cell comprising the nucleic acid molecule according to .21. A host cell comprising the nucleic acid molecule according to .22. A host cell comprising the nucleic acid molecule according to .23. A host cell comprising the nucleic acid molecule according to .24. A method for producing a DCC-fusion protein said method comprising:expressing a nucleic acid in a eukaryotic host cell; and recovering the DCC-fusion protein from said cell or the cell culture supernatant.25. A method according to claim 24 , wherein said DCC-fusion protein has the amino acid sequence of SEQ ID NO: 2.26. The method according to claim 24 , wherein said DCC-fusion protein has the amino acid sequence of SEQ ID NO: 3.27. A pharmaceutical composition comprising: a DCC-fusion protein claim 24 , a vector or a host; and a pharmaceutically ...

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH AN ANTI-BCL-2 ACTIVE AGENT

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and an anti-Bcl-2 active agent. 1. A composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent.2. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.63. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.4. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).5. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.6. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is selected from the group consisting of Oblimersen claim 1 , SPC-2996 claim 1 , RTA-402 claim 1 , Gossypol claim 1 , AT-101 claim 1 , Obatoclax mesylate claim 1 , A-371191 claim 1 , A-385358 claim 1 , A-438744 claim 1 , ABT-737 claim 1 , AT-101 claim 1 , BL-11 claim 1 , BL-193 claim 1 , GX-15-003 claim 1 , 2-Methoxyantimycin A3 claim 1 , HA-14-1 claim 1 , KF-67544 claim 1 , Purpurogallin claim 1 , TP-TW-37 claim 1 , YC-137 and Z-24.7. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is ...

Bispecific Anti-VEGF/Anti-ANG-2 Antibodies and their use in the Treatment of Ocular Vascular Diseases

The present invention relates to bispecific antibody against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2) of human IgG1 or IgG4 subclass with mutations I253A, H310A, and H435A, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A method for the reduction of the viscosity of an antibody wherein the antibody comprises a constant heavy chain region of human IgG1 or human IgG4 subclass (derived from human origin and)wherein the method comprisesthe modification of the antibody constant heavy chain region of human IgG1 or human IgG4 subclass with the mutations I253A, H310A, and H435A (numbering according to EU Index of Kabat).2. The method of claim 1 , wherein the antibody is a bispecific antibody comprising a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2 claim 1 , whereini) said first antigen-binding site specifically binding to VEGF comprises in the heavy chain variable domain a CDR3H region of SEQ ID NO: 1, a CDR2H region of SEQ ID NO: 2, and a CDR1H region of SEQ ID NO:3, and in the light chain variable domain a CDR3L region of SEQ ID NO: 4, a CDR2L region of SEQ ID NO:5, and a CDR1L region of SEQ ID NO:6; andii) said second antigen-binding site specifically binding to ANG-2 comprises in the heavy chain variable domain a CDR3H region of SEQ ID NO: 9, a CDR2H region of, SEQ ID NO: 10, and a CDR1H region of SEQ ID NO: 11, and in the light chain variable domain a CDR3L region of SEQ ID NO: 12, a CDR2L region of SEQ ID NO: 13, and a CDR1L region of SEQ ID NO: 14, and whereiniii) the bispecific antibody comprises a constant heavy chain region of human IgG1 or human IgG4 subclass (derived from human origin and) comprising the mutations I253A, H310A, and H435A (numbering according to EU Index of Kabat).3. The method of claim 2 , wherein the bispecific antibody comprises a ...

INTERLEUKIN-2 FUSION PROTEINS AND USES THEREOF

The present invention generally relates to fusion proteins of immunoglobulins and interleukin-2 (IL-2). In addition, the present invention relates to polynucleotides encoding such fusion proteins, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the fusion proteins of the invention, and to methods of using them in the treatment of disease. 1. A fusion protein comprising (i) an immunoglobulin molecule comprising a modification reducing binding affinity of the immunoglobulin molecule to an Fc receptor as compared to a corresponding immunoglobulin molecule without said modification , and (ii) two interleukin-2 (IL-2) molecules.2. The fusion protein of claim 1 , wherein said immunoglobulin molecule is an IgG-class immunoglobulin molecule.3. The fusion protein of claim 2 , wherein said IgG-class immunoglobulin molecule is IgG.4. The fusion protein of claim 1 , wherein said immunoglobulin molecule is a human immunoglobulin molecule.5. The fusion protein of claim 1 , wherein said immunoglobulin molecule is not capable of specific binding to an antigen.6. The fusion protein of claim 1 , wherein said immunoglobulin molecule comprises a heavy chain variable region sequence based on the human Vh3-23 germline sequence.7. The fusion protein of claim 1 , wherein said immunoglobulin molecule comprises the heavy chain variable region sequence of SEQ ID NO: 9.8. The fusion protein of claim 1 , wherein said immunoglobulin molecule comprises a light chain variable region sequence based on the human Vk3-20 germline sequence.9. The fusion protein of claim 1 , wherein said immunoglobulin molecule comprises the light chain variable region sequence of SEQ ID NO: 11.10. The fusion protein of claim 1 , wherein said Fc receptor is an Fcγ receptor.11. The fusion protein of claim 1 , wherein said Fcγ receptor is a human Fcγ receptor.12. The fusion protein of claim 11 , wherein said Fcγ receptor is a human Fcγ receptor.13. The ...

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH BENDAMUSTINE

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with bendamustine for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and bendamustine. 1. Use of an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 , for the manufacture of a medicament for the treatment of cancer in combination with bendamustine.2. Use according to characterized in that the amount of fucose of is between 40% and 60%.3. Use according to characterized in that the amount of fucose of is 50% or less.4. Use according to any one of to characterized in that said cancer is a CD20 expressing cancer.5. Use according to characterized in that said CD20 expressing cancer is a B-Cell Non-Hodgkin's lymphoma (NHL).6. Use according to any one of to claim 4 , characterized in that said afucosylated anti-CD20 antibody is a type II anti-CD20 antibody.7. Use according to claim 6 , characterized in that said antibody is a humanized B-Ly1 antibody.8. Use according to any one of to claim 6 , characterized in that one or more additional other cytotoxic claim 6 , chemotherapeutic or anti-cancer agents claim 6 , or compounds or ionizing radiation that enhance the effects of such agents are administered.9. Use according to any one of to claim 6 , characterized in that said humanized B-Ly1 antibody is administered in a dosage of 800 to 1200 mg on day 1 claim 6 , 8 claim 6 , 15 of a 6-week-dosage-cycle and then in a dosage of 800 to 1200 mg on day 1 of up to five 4-week-dosage-cycles claim 6 , and bendamustine is administered in a dosage of 80 mg/mto 110 mg/mon day 1 and 2 of up to six 4-week-dosage-cycles.10. A composition comprising an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 and bendamustine for the treatment of cancer. ...

Immunotherapy

The present invention provides combinations of (a) an immunoconjugate comprising at least one antigen-binding moiety and an effector moiety, and (b) an antibody engineered to have increased effector function, for use in treating a disease in an individual in need thereof. Further provided are pharmaceutical compositions comprising the combinations, and methods of using them. 1. A combination of (a) an immunoconjugate comprising at least one antigen-binding moiety and an effector moiety , and (b) an antibody engineered to have increased effector function , for use in treating a disease in an individual in need thereof.2. The combination of claim 1 , wherein the effector moiety is a cytokine.3. The combination of or claim 1 , wherein the effector moiety is a cytokine selected from the group consisting of IL-2 claim 1 , GM-CSF claim 1 , IFN-α claim 1 , and IL-12.4. The combination of any one of to claim 1 , wherein the effector moiety is IL-2.5. The combination of claim 4 , wherein the IL-2 effector moiety is a mutant IL-2 effector moiety comprising at least one amino acid mutation claim 4 , particularly an amino acid substitution claim 4 , that reduces or abolishes the affinity of the mutant IL-2 effector moiety to the α-subunit of the IL-2 receptor but preserves the affinity of the mutant IL-2 effector moiety to the intermediate-affinity IL-2 receptor claim 4 , compared to the non-mutated IL-2 effector moiety.6. The combination of any one of to claim 4 , wherein the antigen-binding moiety is an antibody or an antibody fragment.7. The combination of any one of to claim 4 , wherein the antigen-binding moiety is selected from a Fab molecule and a scFv molecule.8. The combination of any one of to claim 4 , wherein the immunoconjugate comprises a first and a second antigen-binding moiety.9. The combination of claim 8 , wherein each of said first and said second antigen-binding moieties is a Fab molecule.10. The combination of or claim 8 , wherein the effector moiety ...

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH INCREASED ANTIBODY DEPENDENT CELLULAR CYTOTOXITY (ADCC)

The present invention is directed to a pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity (ADCC); and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide, vincristine and doxorubicine. The present invention is also directed to a method for the treatment of a CD20 expressing cancer, comprising administering to a patient in need of such treatment (i) an effective first amount of a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity; and (ii) an effective second amount of one or more chemotherapeutic agents selected from the group consisting of cyclophosphamide, vincristine and doxorubicine. 1. A pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity; and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide , vincristine and doxorubicine.2. A composition according to wherein said type II anti-CD20 antibody is a glycoengineered claim 1 , humanized B-Ly1 antibody.3. A composition according to wherein said composition comprises said type II anti-CD20 antibody claim 1 , cyclophosphamide and vincristine.4. A composition according to wherein said composition comprises said type II anti-CD20 antibody and doxorubicine.5. A composition according to wherein said composition comprises said type II anti-CD20 antibody and cyclophosphamide.6. A composition according to wherein said composition comprises said type II anti-CD20 antibody claim 1 , cyclophosphamide claim 1 , vincristine and doxorubicine.7. A composition according to comprising also a pharmaceutically-acceptable carrier.8. A composition according to comprises also a corticosteroid.9. A composition according to wherein said corticosteroid is prednisone.10. A method for the treatment of a CD20 expressing cancer claim 7 , comprising administering to a patient in need of such ...

ANTIBODIES AGAINST HUMAN ANGIOPOIETIN 2

The present invention relates to a method of treating a disease or disorder in a patient comprising administering, to a patient in need of such treatment, an antibody which binds specifically to human angiopoietin-2 (ANG-2). The present invention also relates to a method for preventing metastasis in a patient suffering from primary cancer comprising administering, to a patient in need of such preventative treatment, an antibody which binds specifically to human angiopoietin-2 (ANG-2). 1. A method of treating a disease or disorder in a patient comprising administering , to a patient in need of such treatment , an antibody which binds specifically to human angiopoietin-2 (ANG-2) , wherein said antibody comprises:(A) a heavy chain variable domain which comprises a CDR3 region of SEQ ID NO: 33, a CDR2 region of SEQ ID NO: 34 and a CDR1 region of SEQ ID NO: 35;(B) a light chain variable domain which comprises a CDR3 region of SEQ ID NO: 36, a CDR2 region of SEQ ID NO: 37 and a CDR1 region of SEQ ID NO: 38.2. A method according to wherein said disease or disorder is cancer.3. A method according to wherein said disease or disorder is a vascular disease.4. A method according to wherein said disease or disorder is a retinopathy.5. A method for preventing metastasis in a patient suffering from primary cancer comprising administering claim 3 , to a patient in need of such preventative treatment claim 3 , an antibody which binds specifically to human angiopoietin-2 (ANG-2) claim 3 , wherein said antibody comprises:(A) a heavy chain variable domain which comprises a CDR3 region of SEQ ID NO: 33, a CDR2 region of SEQ ID NO: 34 and a CDR1 region of SEQ ID NO: 35;(B) a light chain variable domain which comprises a CDR3 region of SEQ ID NO: 36, a CDR2 region of SEQ ID NO: 37 and a CDR1 region of SEQ ID NO: 38. This application is a division of U.S. application Ser. No. 13/358,831, filed Jan. 26, 2012, now pending; which is a continuation of U.S. application Ser. No. 12/635,825, ...

ANTIBODIES AGAINST HUMAN ANGIOPOIETIN 2

The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. An isolated nucleic acid encoding a heavy chain of an antibody which binds specifically to human angiopoietin-2 (ANG-2) , wherein the variable domain of said heavy chain comprises a CDR3 region having the amino acid sequence of SEQ ID NO: 33.2. An isolated nucleic acid according to wherein said variable domain of said heavy chain further comprises a CDR2 region having the amino acid sequence of SEQ ID NO: 34 and a CDR1 region having the amino acid sequence of SEQ ID NO: 35.3. An isolated nucleic acid according to wherein said variable domain of said heavy chain is has the amino acid sequence of SEQ ID NO: 39.4. An isolated nucleic acid encoding a light chain of an antibody which binds specifically to human angiopoietin-2 (ANG-2) claim 1 , wherein the variable domain of said light chain comprises a CDR3 region having the amino acid sequence of SEQ ID NO: 36.5. An isolated nucleic acid according to wherein said variable domain of said light chain further comprises a CDR2 region having the amino acid sequence of SEQ ID NO: 37 and a CDR1 region having the amino acid sequence of SEQ ID NO: 38.6. An isolated nucleic acid according to wherein said variable domain of said light chain is has the amino acid sequence of SEQ ID NO: 40.7. An expression vector characterized in comprising a nucleic acid according to for the expression of said antibody in a prokaryotic or eukaryotic host cell.8. An expression vector characterized in comprising an isolated nucleic acid according to for the expression of said antibody in a prokaryotic or eukaryotic host cell.9. A prokaryotic or eukaryotic host cell comprising a vector according to .10. A prokaryotic or eukaryotic host cell comprising a vector according to .11. A prokaryotic or eukaryotic host cell comprising: a vector comprising an ...

IMMUNOTHERAPY

The present invention provides combinations of (a) an immunoconjugate comprising a first antibody engineered to have reduced effector function and an effector moiety, and (b) a second antibody engineered to have increased effector function, for use in treating a disease in an individual in need thereof. Further provided are pharmaceutical compositions comprising the combinations, and methods of using them. 1. A method of treating a disease in an individual comprising administering to the individual a combination of (a) an immunoconjugate comprising a first antibody engineered to have reduced effector function and an effector moiety , and (b) a second antibody engineered to have increased effector function , in a therapeutic effective amount.2. The method of claim 1 , wherein the effector moiety is a cytokine.3. The method of claim 1 , wherein the effector moiety is a cytokine selected from the group consisting of IL-2 claim 1 , GM-CSF claim 1 , IFN-α claim 1 , and IL-12.4. The method of claim 1 , wherein the effector moiety is IL-2.5. The method of claim 4 , wherein the IL-2 effector moiety is a mutant IL-2 effector moiety comprising at least one amino acid mutation claim 4 , particularly an amino acid substitution claim 4 , that reduces or abolishes the affinity of the mutant IL-2 effector moiety to the α-subunit of the IL-2 receptor but preserves the affinity of the mutant IL-2 effector moiety to the intermediate-affinity IL-2 receptor claim 4 , compared to the non-mutated IL-2 effector moiety.6. The method of claim 1 , wherein the first antibody is a full-length antibody claim 1 , particularly an IgG class antibody claim 1 , more particularly and IgGsub-class antibody.7. The method of claim 1 , wherein the effector moiety shares an amino- or carboxy-terminal peptide bond with the first antibody.8. The method of claim 1 , wherein the first antibody is engineered to have reduced binding to an activating Fc receptor claim 1 , particularly reduced binding to human Fc ...

Light source, and optical coherence tomography module

An optical module includes a light source. The light source can be a swept wavelength light source, and optical module includes a wavemeter. The wavemeter includes a wavemeter tap capable of directing a wavemeter portion of light produced by the light source away from a main beam, a wavelength selective filter arranged to receive the wavemeter portion, a first wavemeter detector arranged to measure a transmitted radiation intensity of radiation transmitted through the filter, and a second wavemeter detector arranged to measure a non-transmitted radiation intensity of radiation not transmitted through but reflected by the filter. In addition, an optical coherence tomography apparatus includes the optical module.

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH INCREASED ANTIBODY DEPENDENT CELLULAR CYTOTOXITY (ADCC)

The present invention is directed to a pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity (ADCC); and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide, vincristine and doxorubicine. The present invention is also directed to a method for the treatment of a CD20 expressing cancer, comprising administering to a patient in need of such treatment (i) an effective first amount of a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity; and (ii) an effective second amount of one or more chemotherapeutic agents selected from the group consisting of cyclophosphamide, vincristine and doxorubicine. 1. A pharmaceutical composition comprising: (A) a type II anti-CD20 antibody with increased antibody dependent cellular cytotoxicity; and (B) a chemotherapeutic agent selected from the group consisting of: cyclophosphamide , vincristine and doxorubicine.2. A composition according to wherein said type II anti-CD20 antibody is a glycoengineered claim 1 , humanized B-Ly1 antibody.3. A composition according to wherein said composition comprises said type II anti-CD20 antibody claim 1 , cyclophosphamide and vincristine.4. A composition according to wherein said composition comprises said type II anti-CD20 antibody and doxorubicine.5. A composition according to wherein said composition comprises said type II anti-CD20 antibody and cyclophosphamide.6. A composition according to wherein said composition comprises said type II anti-CD20 antibody claim 1 , cyclophosphamide claim 1 , vincristine and doxorubicine.7. A composition according to comprising also a pharmaceutically-acceptable carrier.8. A composition according to comprises also a corticosteroid.9. A composition according to wherein said corticosteroid is prednisone.10. A method for the treatment of a CD20 expressing cancer claim 7 , comprising administering to a patient in need of such ...

METHODS OF TREATING CEA-POSITIVE CANCERS USING PD-1 AXIS BINDING ANTAGONISTS AND ANTI-CEA/ANTI-CD3 BISPECIFIC ANTIBODIES

The invention provides compositions and methods for treating CEA-positive cancers. The method comprising administering a PD-1 axis binding antagonist and a bispecific antibody that targets CEA and CD3. 1. A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a human PD-1 axis binding antagonist and an anti-CEA/anti-CD3 antibody.2. The method of claim 1 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist claim 1 , a PD-L1 binding antagonist and a PD-L2 binding antagonist.3. The method of or claim 1 , wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.4. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.5. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.6. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.7. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.8. The method of claim 3 , wherein the PD-1 binding antagonist is an antibody.9. The method of claim 3 , wherein the PD-1 binding antagonist is selected from the group consisting of MDX 1106 (nivolumab) claim 3 , MK-3475 (pembrolizumab) claim 3 , CT-011 (pidilizumab) claim 3 , MEDI-0680 (AMP-514) claim 3 , PDR001 claim 3 , REGN2810 claim 3 , and BGB-108.10. The method of claim 2 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.11. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.12. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.13. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.14. The method of claim 10 , wherein the PD-L1 binding ...

USER INTERFACE TRANSITIONS AND OPTIMIZATIONS FOR FOLDABLE COMPUTING DEVICES

A foldable computing device can be configured to provide a user interface (UI) optimization that enables an application window to be presented in a predictable location when an application is launched, a UI optimization that enables an application window to be moved to an active display area, a UI optimization that enables a modal UI element to be presented in such a way that it does not overlap a seam on the device, a UI optimization that enables an image presented by the device to be adjusted to maintain a view of the focal point of the image across device posture or orientation changes, a UI optimization that enables the device to transition between UI modes optimized for front-facing and world-facing image capture, and/or a UI optimization that enables the device to provide a UI for instructing a user to flip the device when a biometric sensor is in use. 1. A computer-implemented method , comprising:displaying a first application window for an application in a first display region of a foldable computing device while the foldable computing device is in an unbent posture;detecting that the foldable computing device has transitioned from the unbent posture to a bent posture; displaying a second application window for the application in a second display region of the foldable computing device; and', 'displaying a third application window for the application in a third display region of the foldable computing device, wherein the second display region and the third display region are separated by an artificial hardware seam., 'responsive to detecting that the foldable computing device has transitioned from the unbent posture to the bent posture2. The computer-implemented method of claim 1 , wherein:the foldable computing device is configured to operate in a single display region mode that includes the first display region as an only display region while the foldable computing device is in the unbent posture; andthe foldable computing device is configured to operate ...

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. One or more isolated polynucleotides encoding a T cell activating bispecific antigen-binding molecule , wherein the T cell activating bispecific antigen-binding molecule comprises:(i) a first antigen-binding moiety which is a Fab molecule capable of specific binding to CD3, the first antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7, wherein the first antigen-binding moiety is a crossover Fab molecule, and wherein either the variable or the constant regions of the Fab light chain and the Fab heavy chain are exchanged;(ii) a second antigen-binding moiety and a third antigen-binding moiety, each of which is a Fab molecule capable of specific binding to CEA, the second and third antigen-binding moieties each comprising the heavy chain complementarity determining region (CDR) 1 of SEQ ID NO: 24, the heavy chain CDR 2 of SEQ ID NO: 25, the heavy chain CDR 3 of SEQ ID NO: 26, the light chain CDR 1 of SEQ ID NO: 28, the light chain CDR 2 of SEQ ID NO: 29, and the light chain CDR 3 of SEQ ID NO: 30; and(iii) an Fc domain comprising a first subunit and a second subunit capable of stable association, wherein the second antigen-binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the Fab heavy chain of the first antigen-binding moiety, and the first antigen-binding ...

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A method of treating a disease in an individual , the method comprising administering to the individual a therapeutically effective amount of a composition comprising a T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form , wherein the T cell activating bispecific antigen-binding molecule comprises:(i) a first antigen-binding moiety which is a Fab molecule capable of specific binding to CD3, the first antigen-binding moiety comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7, wherein the first antigen-binding moiety is a crossover Fab molecule, and wherein either the variable or the constant regions of the Fab light chain and the Fab heavy chain are exchanged;(ii) a second antigen-binding moiety and a third antigen-binding moiety, each of which is a Fab molecule capable of specific binding to CEA, the second and third antigen-binding moieties each comprising the heavy chain complementarity determining region (CDR) 1 of SEQ ID NO: 24, the heavy chain CDR 2 of SEQ ID NO: 25, the heavy chain CDR 3 of SEQ ID NO: 26, the light chain CDR 1 of SEQ ID NO: 28, the light chain CDR 2 of SEQ ID NO: 29, and the light chain CDR 3 of SEQ ID NO: 30; and(iii) an Fc domain comprising a first subunit and a second subunit capable of stable association, wherein the second antigen-binding moiety is ...

BISPECIFIC ANTI-VEGF/ANTI-ANG-2 ANTIBODIES

The present invention relates to bispecific antibodies against human VEGF and against human ANG-2, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A method of treatment of a patient suffering from a disease or disorder which is cancer or a vascular disease , said method comprising the step of administering a bispecific antibody to a patient in the need of such treatment , said bispecific antibody being one that binds specifically to human vascular endothelial growth factor (VEGF) and human angiopoietin-2 (ANG-2) and comprises a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2 , wherein:i) said antigen-binding sites each comprise an antibody heavy chain variable domain and an antibody light chain variable domain; a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 9, SEQ ID NO: 17, and SEQ ID NO: 94;', 'a CDR2 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 18, and SEQ ID NO: 95;', 'and a CDR1 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:3, SEQ ID NO: 11, SEQ ID NO: 19, and SEQ ID NO: 96, and', 'in the light chain variable domain:', 'a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, and SEQ ID NO: 97,', 'a CDR2 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:5, SEQ ID NO: 13, SEQ ID NO: 21, and SEQ ID NO: 98; and', 'a CDR1 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:6, SEQ ID NO: 14, SEQ ID NO: 22, and SEQ ID NO: 99; and, 'ii) said first antigen-binding site comprises in the heavy chain variable domain a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 25, SEQ ID ...

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH A SELECTIVE BCL-2 INHIBITOR

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer. 1. A method for the treatment of a cancer in a human in need thereof comprising administering to said human an effective amount of a GA101 antibody or 2-(1H-pyrrolo[2 ,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4 ,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-N-(3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof for one or more dosing periods , followed by co-administering an effective amount of said GA101 antibody and 2-(1H-pyrrolo[2 ,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4 ,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-N-(3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof for one or more dosing periods.2. A method for the treatment of a cancer in a human in need thereof comprising administering to said human an effective amount of a GA101 antibody or 2-(1H-pyrrolo[2 ,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4 ,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-N-(3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof for 0 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 or 14 days , followed by co-administering an effective amount of said GA101 antibody and 2-(1H-pyrrolo[2 ,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4 ,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-N-(3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenylsulfonyl)benzamide or a pharmaceutically acceptable salt thereof for one or more dosing periods.3. The method of claim 1 , wherein an effective amount of said GA101 antibody is administered once every dosing period for 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 or 6 cycles ...

ANTIBODIES BINDING TO CD3

The present invention generally relates to antibodies that bind to CD3, including multispecific antibodies e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease. 1. An antibody that specifically binds to CD3 , wherein the antibody comprises a first antigen binding domain , comprising (a) a VH comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 2, a HCDR 2 of SEQ ID NO: 4, and a HCDR 3 of SEQ ID NO: 10,', '(b) a VH comprising a HCDR 1 of SEQ ID NO: 2, a HCDR 2 of SEQ ID NO: 4, and a HCDR 3 of SEQ ID NO: 12,', '(c) a VH comprising a HCDR 1 of SEQ ID NO: 2, a HCDR 2 of SEQ ID NO: 5, and a HCDR 3 of SEQ ID NO: 9,', '(d) a VH comprising a HCDR 1 of SEQ ID NO: 3, a HCDR 2 of SEQ ID NO: 6, and a HCDR 3 of SEQ ID NO: 11, and', '(e) a VH comprising a HCDR 1 of SEQ ID NO: 3, a HCDR 2 of SEQ ID NO: 7, and a HCDR 3 of SEQ ID NO: 13,, '(i) a heavy chain variable region (VH) selected from the group consisting of'}and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 20, a LCDR 2 of SEQ ID NO: 21 and a LCDR 3 of SEQ ID NO: 22, or an antigen binding domain fragment thereof.2. The antibody of claim 1 , whereinthe VH comprises an amino acid sequence that is at least about 95%, 96%, 97%, 98%, 99% or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 15, SEQ ID NO: 17 and SEQ ID NO: 19, orthe VL comprises an amino acid sequence that is at least about 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 23,or both the VH and the VL.3. An antibody that specifically binds to CD3 claim 1 , wherein the antibody comprises a first antigen binding ...

Dial Control for Addition and Reversal Operations

In one example, a method for modifying input with a dial includes creating a queue of input actions corresponding to one or more atomic operations for an application. The method can also include detecting a dial action from a dial, the dial action indicating a reversal operation for removing at least one input action from the queue of input actions or an addition operation for adding at least one input action to the queue of input actions. Furthermore, the method can include generating an intermediate representation of the one or more atomic operations based on the dial action from the dial. 1. A system for modifying input , the system comprising:memory; and create a queue of input actions corresponding to one or more atomic operations for an application;', 'detect a dial action from a dial, the dial action indicating a reversal operation for removing at least one input action from the queue of input actions or an addition operation for adding at least one input action to the queue of input actions; and', 'generate an intermediate representation of the one or more atomic operations based on the dial action from the dial., 'at least one processor configured to2. The system of claim 1 , wherein the dial is an analog dial coupled to the exterior of the system or the dial is a separate hardware component that transmits the dial action to the system using a wireless protocol or using a wired connection.3. The system of claim 1 , wherein the dial is an analog user interface dial displayed by the system.4. The system of claim 1 , wherein the queue of input actions corresponds to a series of points along an atomic digital ink stroke operation claim 1 , and wherein the dial action modifies the atomic digital ink stroke operation using the reversal operation comprising removing at least one of the points along the atomic digital ink stroke.5. The system of claim 1 , wherein the queue of input actions corresponds to an atomic character operation claim 1 , and wherein the dial ...

Compounds for electronic devices

The present invention relates to compounds of formula (I), to processes for producing the compounds, and to electronic devices containing at least one compound of formula (I).

AGONISTIC CD28 ANTIGEN BINDING MOLECULES TARGETING HER2

The present invention relates to Her2-targeted bispecific agonistic CD28 antigen binding molecules characterized by monovalent binding to CD28, methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same. 1. A bispecific agonistic CD28 antigen binding molecule characterized by monovalent binding to CD28 , comprising(a) a first antigen binding domain capable of specific binding to CD28,(b) a second antigen binding domain capable of specific binding to an antigen binding domain capable of specific binding to human epidermal growth factor receptor-2 (Her2), and(c) a Fc domain composed of a first and a second subunit capable of stable association comprising one or more amino acid substitution that reduces the binding affinity of the antigen binding molecule to an Fc receptor and/or effector function, [{'sub': H', 'L, '(i) a heavy chain variable region (VHer2) comprising a heavy chain complementary determining region CDR-H1 of SEQ ID NO: 2, a CDR-H2 of SEQ ID NO: 3, and a CDR-H3 of SEQ ID NO: 4, and a light chain variable region (VHer2) comprising a light chain complementary determining region CDR-L1 of SEQ ID NO: 5, a CDR-L2 of SEQ ID NO: 6 and a CDR-L3 of SEQ ID NO: 7; or'}, {'sub': H', 'L, '(ii) a heavy chain variable region (VHer2) comprising a heavy chain complementary determining region CDR-H1 of SEQ ID NO: 10, a CDR-H2 of SEQ ID NO: 11, and a CDR-H3 of SEQ ID NO: 12, and a light chain variable region (VHer2) comprising a light chain complementary determining region CDR-L1 of SEQ ID NO: 13, a CDR-L2 of SEQ ID NO: 14 and a CDR-L3 of SEQ ID NO: 15; or'}, {'sub': H', 'L, '(iii) a heavy chain variable region (VHer2) comprising a heavy chain complementary determining region CDR-H1 of SEQ ID NO: 132, a CDR-H2 of SEQ ID NO: 133, and a CDR-H3 of SEQ ID NO: 134, and a light chain variable region (VHer2) comprising a light chain complementary determining region CDR-L1 of SEQ ID NO: 135, a CDR-L2 of SEQ ID NO: 136 and a ...

Latency reduction in remote rendering with adaptive phase shifting

Sending streamed data packets from a producer to a consumer. A method includes, at a first entity, sending consumable data packets from the first entity to a second entity at a first consumable packet rate. The method further includes receiving a first phase delta from the second entity, wherein the first phase delta is computed from transmission jitter, computed from timing information in the consumable data packets. The method further includes sending from the first entity consumable data packets at a second consumable packet rate, the second consumable packet rate being dependent on the first phase delta.

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH A CD22 ANTIBODY-DRUG CONJUGATE

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with a CD22 antibody-drug conjugate for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and a CD22 antibody-drug conjugate. 1: An afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 , for the treatment of cancer in combination with a CD22 antibody-drug conjugate.2: The antibody according to claim 1 , characterized in that said cancer is a CD20 expressing cancer.3: The antibody according to claim 1 , characterized in that said CD20 expressing cancer is a lymphoma or lymphocytic leukemia.4: The antibody according to claim 1 , characterized in that said anti-CD20 antibody is a humanized B-Ly1 antibody.5: The antibody according to claim 1 , characterized in that said anti-CD20 antibody is obinutuzumab.6: The antibody according to claim 1 , characterized in that one or more additional other cytotoxic claim 1 , chemotherapeutic or anti-cancer agents claim 1 , or compounds or ionizing radiation that enhance the effects of such agents are administered.7: The antibody according to claim 1 , characterized in that said CD22 antibody in the CD22 antibody-drug conjugate comprises (a) an HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs:9 claim 1 , 10 claim 1 , 19-23 claim 1 , 32 and 33 claim 1 , and (b) at least one claim 1 , two claim 1 , three claim 1 , four claim 1 , or five HVRs selected from:(1) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:2;(2) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:4;(3) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:6;(4) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:12; and(5) an HVR-L3 comprising an amino acid sequence of SEQ ID NO:14.8: The antibody according to claim 1 , characterized in that said CD22 antibody binds to ...

BISPECIFIC ANTIGEN BINDING MOLECULES TARGETING OX40 AND FAP

The invention relates to novel bispecific antigen binding molecules, comprising at least two antigen binding domains capable of specific binding to OX40 and a particular antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP), and to methods of producing these molecules and to methods of using the same. 1. A bispecific antigen binding molecule , comprising:(a) at least two antigen binding domains capable of specific binding to OX40,{'sub': H', 'L, '(b) an antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP) comprising a heavy chain variable region (VFAP) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:3, (ii) CDR-H2 comprising the amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:11 and SEQ ID NO:12, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region (VFAP) comprising (iv) CDR-L1 comprising the amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:13 and SEQ ID NO:14, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:7, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:8, and'}(c) a Fc region composed of a first and a second subunit capable of stable association.2. The bispecific antigen binding molecule of claim 1 , wherein the Fc region comprises one or more amino acid substitution that reduces the binding affinity of the antibody to an Fc receptor and/or effector function.3. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to FAP comprises:{'sub': 'H', 'a heavy chain variable region (VFAP) comprising an amino acid sequence that is at least about 90% identical to the amino acid sequence of SEQ ID NO:9, and'}{'sub': 'L', 'a light chain variable region (VFAP) comprising an amino acid sequence that is at least about 90% identical to the amino acid sequence of SEQ ID NO:10.'}4. The ...

INTERLEUKIN-2 FUSION PROTEINS AND USES THEREOF

The present invention generally relates to fusion proteins of immunoglobulins and interleukin-2 (IL-2). In addition, the present invention relates to polynucleotides encoding such fusion proteins, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the fusion proteins of the invention, and to methods of using them in the treatment of disease. 146-. (canceled)47. A method for treating or preventing an autoimmune disease , said method comprising: administering a pharmaceutical composition comprising a fusion protein comprising (i) an immunoglobulin molecule comprising a modification reducing binding affinity of the immunoglobulin molecule to an Fc receptor as compared to a corresponding immunoglobulin molecule without said modification , and (ii) two interleukin-2 (IL-2) molecules to a patient.48. The method of claim 47 , wherein said autoimmune disease is selected from the group consisting of type 1 diabetes claim 47 , systemic lupus erythematosus claim 47 , Crohn's disease and multiple sclerosis.49. A method for treating or preventing transplant rejection or graft-versus-host disease said method comprising administering a pharmaceutical composition comprising a fusion protein comprising (i) an immunoglobulin molecule comprising a modification reducing binding affinity of the immunoglobulin molecule to an Fc receptor as compared to a corresponding immunoglobulin molecule without said modification claim 47 , and (ii) two interleukin-2 (IL-2) molecules to a patient.50. A method for selectively activating regulatory T cells in vitro or in vivo claim 47 , said method comprising administering a pharmaceutical composition comprising a fusion protein comprising (i) an immunoglobulin molecule comprising a modification reducing binding affinity of the immunoglobulin molecule to an Fc receptor as compared to a corresponding immunoglobulin molecule without said modification claim 47 , and (ii) two interleukin-2 (IL- ...

C-TERMINALLY FUSED TNF FAMILY LIGAND TRIMER-CONTAINING ANTIGEN BINDING MOLECULES

The invention relates to novel TNF family ligand trimer-containing antigen binding molecules comprising (a) one Fab domain capable of specific binding to a target cell antigen, (b) a Fc domain composed of a first and a second subunit capable of stable association, and (c) a first polypeptide comprising two ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by a peptide linker and a second polypeptide comprising one ectodomain of said TNF ligand family member or a fragment thereof, wherein the first polypeptide is fused at its N-terminus to the C-terminus of one of the subunits of the Fc domain and wherein the second polypeptide is fused at its N-terminus to the C-terminus of the other subunit of the Fc domain, wherein the TNF family ligand trimer-containing antigen binding molecule is monovalent for the binding to the target cell antigen. 1. A TNF family ligand trimer-containing antigen binding molecule comprising(a) one Fab domain capable of specific binding to a target cell antigen,(b) a Fc domain composed of a first and a second subunit capable of stable association, and(c) a first polypeptide comprising two ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by a peptide linker and a second polypeptide comprising one ectodomain of said TNF ligand family member or a fragment thereof, wherein the first polypeptide is fused at its N-terminus to the C-terminus to one of the subunits of the Fc domain and wherein the second polypeptide is fused at its N-terminus to the C-terminus of the other subunit of the Fc domain,wherein the TNF family ligand trimer-containing antigen binding molecule is monovalent for the binding to the target cell antigen.2. The TNF family ligand trimer-containing antigen binding molecule of claim 1 , wherein the TNF ligand family member costimulates human T-cell activation.3. The TNF family ligand trimer-containing antigen binding molecule of or claim 1 , ...

ANTIBODIES FOR CHELATED RADIONUCLIDES AND CLEARING AGENTS

The present application relates to antibodies which bind specifically to chelated radionuclides, including bispecific antibodies, It further relates to the use of such bispecific antibodies in applications such as radioimmunoimaging and radioimmunotherapy. It additionally relates to clearing agents and useful in such methods. 2. The clearing agent of claim 1 , which is a compound of the following formula:{'br': None, 'sub': 'x', 'dextran-(linker-(M-DOTAM))'}whereindextran is dextran or an aminodextran thereof;linker is a linking moiety;M-DOTAM is DOTAM or said functional variant thereof incorporating a metal ion; andx≥1.3. The clearing agent of claim 1 , wherein x is 20 or more claim 1 , 25 or more claim 1 , 30 or more claim 1 , 35 or more claim 1 , 40 or more claim 1 , or 50 or more.5. The clearing agent of claim 1 , wherein the aminodextran substituted with one or more groups selected from an amino acid and a saccharide other than glucose.6. The clearing agent of claim 1 , wherein the number of DOTAM groups as a percentage of the number of glucose units of the dextran or aminodextran is at least 1% claim 1 , at least 1.5% claim 1 , at least 2% claim 1 , at least 2.5% claim 1 , at least 3% claim 1 , at least 5%.7. The clearing agent of claim 1 , wherein the average molecular weight of the dextran is 200-800 kDa claim 1 , optionally greater than 300 claim 1 , 350 claim 1 , 400 or 450 kDa claim 1 , and optionally less than 700 claim 1 , 650 claim 1 , 600 or 550 kDa claim 1 , optionally about 500 kDa.8. The clearing agent of claim 7 , whereindextran components or clearing agents of less than a molecular weight cut-off have been removed, wherein the molecular weight cut-off is 50 kDa or above, 100 kDa or above or 200 kDa or above.9. The clearing agent of claim 8 , wherein the molecular weight cut-off is in the range 50 kDa-250 kDa or 50 kDa-200 kDa claim 8 , optionally 100 kDa-200 kDa and optionally about 100 kDa claim 8 , 150 kDa or 200 kDa.10. The clearing agent of ...

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH AN ANTI-VEGF

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with an anti-VEGF antibody for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and an anti-VEGF antibody. 1. Use of an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 for the manufacture of a medicament for the treatment of cancer in combination with an anti-VEGF antibody.2. Use according to claims 1 , characterized in that said cancer is a CD20 expressing cancer.3. Use according to to claims 1 , characterized in that said CD20 expressing cancer is a B-Cell Non-Hodgkin's lymphoma (NHL).4. Use according to to claims 1 , characterized in that said anti-CD20 antibody is a humanized B-Ly1 antibody.5. Use according to to claims 1 , characterized in that said anti-VEGF antibody is bevacizumab claims 1 , a B20 series antibody or G6 series antibody.6. Use according to to claims 1 , characterized in that said anti-CD20 antibody is a humanized B-Ly1 antibody and said anti-VEGF antibody is bevacizumab or a B20 series antibody.7. Use according to any one of to claims 1 , characterized in that one or more additional other cytotoxic claims 1 , chemotherapeutic or anti-cancer agents claims 1 , or compounds or ionizing radiation that enhance the effects of such agents are administered.8. A composition comprising a humanized B-Ly1 antibody which afucosylated with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 claims 1 , and bevacizumab or a B20 series antibody claims 1 , for the treatment of cancer.9. A method of treatment of patient suffering from cancer by administering an afucosylated anti-CD20 antibody with an amount of fucose of 60% or less of the total amount of oligosaccharides (sugars) at Asn297 claims 1 , in combination with an anti-VEGF antibody claims 1 , to a ...

BIOMARKER SET FOR IDENTIFYING A SEVERE FORM OF CANCER

The present invention relates to a method for differentiating between i) a severe form of cancer and ii) a mild form of cancer, comprising a) determining the amounts of gene product of at least the genes coding for ribosomal protein S6 (RPS6), nucleoside diphosphate kinase (NME/NDKA), and caveolin-1, in a sample from a subject, b) comparing the amounts obtained in step a) to reference amounts, and c) differentiating between a severe form of cancer and a mild form of cancer, wherein an increased amount of products of the genes coding for RPS6 and NME/NDKA and a decreased amount of product of the gene coding for caveolin-1 are indicative of a severe form of cancer. The invention further relates to the use of antibodies specifically recognizing a polypeptide selected from the list consisting of RPS6, NME/NDKA, and caveolin-1, for differentiating between a severe form of cancer and a mild form of cancer. Furthermore, the invention relates to a detection agent specifically recognizing a polypeptide selected from the list consisting of RPS6, NME/NDKA, and caveolin-1, for use in diagnosing, a device and a kit for differentiating between a severe form of cancer and a mild form of cancer. 121-. (canceled)22. A method for differentiating between a severe form of cancer and a mild form of cancer , comprising:(a) determining the amounts of gene product of at least the genes coding for ribosomal protein S6 (RPS6), nucleoside diphosphate kinase (NME/NDKA), and caveolin-1 in a sample from a subject,(b) comparing the amounts obtained in step (a) to reference amounts, and(c) differentiating between a severe form of cancer and a mild form of cancer, wherein an increased amount of product of the gene coding for RPS6 and an increased amount of product of the gene coding for NME/NDKA and a decreased amount of product of the gene coding for caveolin-1 are indicative of a severe form of cancer.23. The method of claim 22 , wherein:the method in step (a) further comprises determining the ...

Apparatus for curing a tubular liner

The present invention relates to an apparatus for curing resin-impregnated tubular liners by means of high-energy radiation, comprising at least two radiation sources for producing high-energy radiation, wherein the apparatus has a front end, a rear end opposite the front end, two opposite side ends, an upper end and a lower end opposite the upper end, wherein a length of the apparatus, measured from the front end to the rear end, a width of the apparatus, measured from a side end to the opposite side end, and/or a height of the apparatus, measured from the lower into the upper end, is smaller in a transport state than in an operating state, in that at least one element of the apparatus is mounted such that the element can be folded out, displaced, rotated, and/or moved, and wherein at least one further radiation source is arranged to be spaced further apart from at least one further radiation source when in the operating state than in the transport state. The invention further relates to a use of such an apparatus.

TRIMERIC COSTIMULATORY TNF FAMILY LIGAND-CONTAINING ANTIGEN BINDING MOLECULES

The invention relates to novel trimeric costimulatory TNF family ligand-containing antigen binding molecules comprising three fusion polypeptides, each of the three fusion polypeptides comprising (a) an ectodomain of a costimulatory TNF family ligand selected from the group consisting of 4-1BBL, OX40L and GITRL or fragments thereof, (b) a trimerization domain, in particular a trimerization domain derived from human cartilage matrix protein (huCMP) of SEQ ID NO:1, and (c) a moiety capable of specific binding to a target cell antigen, and to methods of producing these molecules and to methods of using the same. 1. A trimeric costimulatory TNF family ligand-containing antigen binding molecule of comprising three fusion polypeptides claim 1 , each of the three fusion polypeptides comprising(a) an ectodomain of a costimulatory TNF family ligand selected from the group consisting of 4-1BBL, OX40L and GITRL or fragments thereof,(b) a trimerization domain derived from human cartilage matrix protein (huCMP) of amino acid sequence of SEQ ID NO:1, and(c) a moiety capable of specific binding to a target cell antigen.2. The trimeric costimulatory TNF family ligand-containing antigen binding molecule of claim 1 , wherein the trimerization domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO:2.3. The trimeric costimulatory TNF family ligand-containing antigen binding molecule of claim 1 , wherein the trimerization domain comprises the amino acid sequence of SEQ ID NO:2.4. The trimeric costimulatory TNF family ligand-containing antigen binding molecule of to claim 1 , wherein the costimulatory TNF family ligand is selected from 4-1BBL and OX40L.5. The trimeric costimulatory TNF family ligand-containing antigen binding molecule of to claim 1 , wherein the costimulatory TNF family ligand is 4-1BBL6. The trimeric costimulatory TNF family ligand-containing antigen binding molecule of any one of to claim 1 , wherein the ectodomain of a TNF family ligand ...

Facilitating Interaction with a Computing Device Based on Force of Touch

A technique is described herein that allows a user to control a user interface presentation provided by a computing device based on a force-dependent manner in which the user engages a surface of a force-sensitive input device. This manner of control allows any user to efficiently interact with the computing device, but is particularly beneficial to users who have motor-related and/or vision-related disabilities. 1. A method for facilitating interaction with a computing device , comprising:receiving input signals from an input device, the input signals including at least one signal component that reflects a degree of force at which a user presses against a surface of the input device;determining, based on the input signals, whether the user has performed a force-dependent actuation in which the user presses the surface of the input device with a prescribed force-dependent signal profile;activating a control mode in response to determining that the user has performed the force-dependent actuation; andproviding an assistive technology user interface experience in response to the control mode that has been activated, the assistive technology user interface experience corresponding to an experience that is configured to assist users with visual and/or motor impairments in interacting with a user interface presentation of the computing device.2. The method of claim 1 ,wherein said determining involves determining that the user has applied the force-dependent actuation to a selected location on the user interface presentation,wherein said activating involves activating an active listening control mode, and receiving additional input signals that are produced in response to detecting information spoken by the user; and', 'interpreting the information spoken by the user with respect to a context established by the selected location., 'wherein said providing involves3. The method of claim 1 ,wherein said determining involves determining that the user has applied the force- ...

DIAGNOSTIC ASSAYS TO DETECT TUMOR ANTIGENS IN CANCER PATIENTS

The present invention generally relates to diagnostic assays using cell cultures, in particular to chimeric antigen receptor (CAR) expressing reporter cell assays to analyze samples, in particular patient samples, to diagnose cancer by quantifying the expression of tumor antigens and/or predicting clinical response to cancer immunotherapies. A further aspect of the present invention is to improve safety of e.g., cancer immunotherapies. 1. A diagnostic assay for determining the presence of a tumor cell in a sample , the diagnostic assay comprising the steps of:a) contacting the sample with an antigen binding molecule comprising an antigen binding domain and a recognition domain, wherein the antigen binding domain comprises a target antigen binding moiety capable of specific binding to the tumor cell; i. a CAR capable of specific binding to the recognition domain, wherein the CAR is operationally coupled to a response element;', 'ii. a reporter gene under the control of the response element; and, 'b) contacting the sample with a chimeric antigen receptor (CAR) expressing reporter T (CAR-T) cell wherein the reporter CAR-T cell comprisesc) determining T cell activation by measuring the expression of the reporter gene to establish the presence of the tumor cell.2. The diagnostic assay of claim 1 , wherein the antigen binding domain is a Fab fragment and the recognition domain is an Fc domain.3. The diagnostic assay of any one of or claim 1 , wherein the antigen binding molecule is an IgG class antibody claim 1 , particularly an IgG1 or IgG4 isotype antibody.4. The diagnostic assay of claim 3 , wherein the recognition domain is a mutated Fc domain claim 3 , wherein the mutated Fc domain comprises at least one amino acid substitution compared to the non-mutated parent Fc domain claim 3 , wherein the CAR is capable of specific binding to the mutated Fc domain but not capable of specific binding to the non-mutated parent Fc domain.5. The diagnostic assay of claim 4 , wherein ...

SELECTION OF ANTIBODIES / ANTIBODY FRAGMENTS

The present invention deals with the selection of antibodies and/or antibody fragments in a selection method. Subjects of the present invention are a method, a system and a computer program product for generating score values for pairs of genes which encode the variable domains of light and heavy chains of antibodies and/or antibody fragments. Antibodies and/or antibody fragments can be selected on the basis of the score values. 1. A method comprising:{'sub': L', 'H', 'L', 'H, 'receiving features relating to Vgenes and Vgenes, wherein the Vgenes and Vgenes encode the variable domains of light and heavy chains of antibodies or antibody fragments, wherein the antibodies or antibody fragments originate from a selection method comprising multiple successive selection cycles, and wherein a result of each selection cycle comprises a pool containing antibodies or antibody fragments;'}{'sub': L', 'H', 'L', 'H, 'forming feature vectors for pairs of Vgenes and Vgenes in the pools, wherein the Vgene and the Vgene of each pair encode variable domains belonging to the same antibody or antibody fragment, and wherein each feature vector for a particular pool comprises the following features{'sub': 'L', 'a count of the Vgene in the particular pool,'}{'sub': 'H', 'a count of the Vgene in the particular pool,'}{'sub': 'L', 'a count of the Vgene in the preceding pool,'}{'sub': 'H', 'a count of the Vgene in the preceding pool,'}{'sub': H', 'L, 'the absolute difference between the count of the Vgene in the particular pool and the count of the Vgene in the particular pool, and'}{'sub': H', 'L, 'the absolute difference between the count of the Vgene in the preceding pool and the count of the Vgene in the preceding pool;'}{'sub': L', 'H, 'identifying enrichment patterns in the feature vectors of the pools, wherein the enrichment patterns show the strength of enrichment of the antibody or antibody fragment with the particular Vgene and Vgene in the selection method;'}{'sub': L', 'H, ' ...

HER2-TARGETING ANTIGEN BINDING MOLECULES COMPRISING 4-1BBL

The invention relates to Her2 targeting 4-1BB agonists, in particular 4-1BBL trimer-containing antigen binding molecules comprising at least one antigen binding domain capable of specific binding to Her2 and their use in the treatment of cancer as well as their use in combination with T-cell activating anti-CD3 bispecific antibodies. 1. A 4-1BBL trimer-containing antigen binding molecule comprising:(a) an antigen binding domain capable of specific binding to Her2, 'wherein the first polypeptide comprises two ectodomains of 4-1BBL or a fragment thereof that are connected to each other by a peptide linker and the second polypeptide comprises one ectodomain of 4-1BBL or a fragment thereof, and', '(b) a first and a second polypeptide that are linked to each other by a disulfide bond,'}(c) an Fc domain composed of a first and a second subunit capable of stable association.2. The 4-1BBL trimer-containing antigen binding molecule of claim 1 , wherein the ectodomain of 4-1BBL or a fragment thereof comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1 claim 1 , SEQ ID NO: 2 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:4 claim 1 , SEQ ID NO:5 claim 1 , SEQ ID NO: 6 claim 1 , SEQ ID NO:7 and SEQ ID NO:8.3. The 4-1BBL trimer-containing antigen binding molecule of claim 1 , wherein the ectodomain of 4-1BBL or a fragment thereof comprises an amino acid sequence of SEQ ID NO:1.4. The 4-1BBL trimer-containing antigen binding molecule of claim 1 , wherein the ectodomain of 4-1BBL or a fragment thereof comprises an amino acid sequence of SEQ ID NO:5.5. The 4-1BBL trimer-containing antigen binding molecule of claim 1 , whereinthe first polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12; andthe second polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:5, SEQ ID NO:3 and SEQ ID NO:4.6. The 4-1BBL trimer-containing ...

DIAGNOSTIC ASSAYS TO DETECT TUMOR ANTIGENS IN CANCER PATIENTS

The present invention generally relates to diagnostic assays using cell cultures, in particular to chimeric antigen receptor (CAR) expressing reporter cell assays to analyze samples, in particular patient samples, to diagnose cancer by quantifying the expression of tumor antigens and/or predicting clinical response to cancer immunotherapies. A further aspect of the present invention is to improve safety of e.g., cancer immunotherapies. 1. A diagnostic assay for determining the presence of a tumor cell in a sample , the diagnostic assay comprising the steps of: i. a CAR capable of specific binding to the tumor cell, wherein the CAR is operationally coupled to a response element;', 'ii. a reporter gene under the control of the response element; and, 'a) contacting the sample with a chimeric antigen receptor (CAR) expressing reporter T (CAR-T) cell wherein the reporter CAR-T cell comprisesb) determining T cell activation by measuring the expression of the reporter gene to establish the presence of the tumor cell.2. The diagnostic assay of claim 1 , wherein the CAR comprises a target antigen binding moiety capable of specific binding to a tumor target antigen.3. The diagnostic assay of claim 2 , wherein the target antigen binding moiety is a Fab fragment.4. The diagnostic assay of any one of to claim 2 , wherein the reporter CAR-T cell is a Jurkat cell.5. The diagnostic assay of any one of to claim 2 , wherein the tumor target antigen is a cell surface antigen and/or receptor.6. The diagnostic assay of any one of or claim 2 , wherein the tumor target antigen is selected from the group consisting of CD20 claim 2 , CD38 claim 2 , CD138 claim 2 , CEA claim 2 , EGFR claim 2 , Fo1R1 claim 2 , HER2 claim 2 , LeY claim 2 , MCSP claim 2 , STEAP1 claim 2 , TYRP1 claim 2 , and WT1 claim 2 , or a fragment thereof.7. The diagnostic assay of any one of to claim 2 , wherein the tumor target antigen is a peptide bound to a molecule of the human major histocompatibility complex (MHC).8 ...

TRI- OR TETRASPECIFIC ANTIBODIES

The present invention relates to tri- or tetraspecific antibodies, their manufacture and use. 126-. (canceled)27. One or more nucleic acid molecules encoding a trispecific or tetraspecific antibody , wherein the antibody comprises:a) a light chain and heavy chain of a full length antibody which specifically binds to a first antigen; andb) a modified light chain and modified heavy chain of a full length antibody which specifically binds to a second antigen, wherein the variable domains VL and VH are replaced by each other, and/or wherein the constant domains CL and CH1 are replaced by each other; andc) one to four antigen binding peptides fused via a peptide connector to the C- or N-terminus of the light chains or heavy chains of a) and/or b) wherein said antigen binding peptides specifically bind one or two further antigens.28. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides comprise one or two antigen binding peptides which specifically bind to one or two further antigens.29. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides comprise one or two antigen binding peptides which specifically bind to a third antigen.30. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides comprise two identical antigen binding peptides which specifically bind to a third antigen.31. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides comprise one antigen binding peptide which specifically binds to a third antigen and one antigen binding peptide which specifically binds to a fourth antigen.32. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides are selected from the group consisting of a scFv fragment and a scFab fragment.33. The one or more nucleic acid molecules of claim 27 , wherein the antigen binding peptides are scFv fragments.34. The one or more nucleic acid molecules of claim 27 , wherein ...

ANTIBODIES AGAINST HUMAN ANGIOPOIETIN 2

The present invention relates to antibodies against human Angiopoietin 2 (anti-ANG-2 antibodies), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. An isolated antibody that specifically binds to human angiopoietin-2 (ANG-2) , wherein the antibody binds to the same epitope as an antibody comprising:(A) a heavy chain variable domain which comprises a CDR3 region having the sequence of SEQ ID NO: 33, a CDR2 region having the sequence of SEQ ID NO: 34 and a CDR1 region having the sequence of SEQ ID NO: 35; and(B) a light chain variable domain which comprises a CDR3 region having the sequence of SEQ ID NO: 36, a CDR2 region having the sequence of SEQ ID NO: 37 and a CDR1 region having the sequence of SEQ ID NO: 38.2. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.3. The antibody of claim 1 , wherein the antibody is a human IgG4 antibody or a human IgG1 antibody.4. A pharmaceutical formulation comprising the antibody of any one of to .5. An isolated antibody that specifically binds to human ANG-2 claim 1 , wherein the antibody binds to the same epitope as an antibody comprising a heavy chain comprising SEQ ID NO: 39 and a light chain comprising SEQ ID NO: 40.6. The antibody of claim 5 , wherein the antibody is a monoclonal antibody.7. The antibody of claim 5 , wherein the antibody is a human IgG4 antibody or a human IgG1 antibody.8. A pharmaceutical formulation comprising the antibody of any one of to . This application is a continuation application of U.S. application Ser. No. 13/693,085, filed Dec. 4, 2012, which is a continuation of U.S. application Ser. No. 13/358,813, filed Jan. 26, 2012, now U.S. Pat. No. 8,361,747, which is a divisional application of U.S. application Ser. No. 12/635,825, filed Dec. 11, 2009, now U.S. Pat. No. 8,133,979, which claims the benefit of European Patent Application No. 08021835.7, filed Dec. 16, 2008. The entire contents of the above-identified ...

BISPECIFIC HER2 ANTIBODIES AND METHODS OF USE

The present invention relates to bispecific HER2 antibodies, novel HER2 antibody variants, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A bispecific antibody specifically binding to HER2 comprising a first antigen binding site specific for extracellular domain II of HER2 and a second antigen binding site specific for extracellular domain IV of HER2 , wherein the bispecific antibody is monovalent for both the extracellular domain II and IV of HER2.2. The bispecific antibody of claim 1 , wherein said antibody induces complement-dependent cytotoxicity to a higher degree than the combination of Pertuzumab or Trastuzumab.3. The bispecific antibody of claim 2 , wherein the complement dependent cytotoxicity of the bispecific antibody is determined by a LDH assay or a complement assay and compared to the complement dependent cytotoxicity of the combination of Pertuzumab and Trastuzumab as determined by the same assay.4. The bispecific antibody of claim 3 , wherein the complement dependent cytotoxicity is determined in vitro on cancer cells claim 3 , preferably on breast cancer cells.5. The bispecific antibody of claim 1 , comprising a first Fab molecule capable of specific binding to extracellular domain II of HER2 and a second Fab molecule capable of specific binding to extracellular domain IV of HER2 claim 1 , wherein the sequence of the variable light chain of the first Fab molecule is identical to the sequence of the variable light chain of the second Fab molecule.6. The bispecific antibody of claim 5 , comprising(a) a first heavy chain comprising a heavy chain CDR1 selected from the group consisting of SEQ ID NO: 55, SEQ ID NO: 58 and SEQ ID NO: 14;a heavy chain CDR 2 selected from the group consisting of SEQ ID NO: 77; SEQ ID NO: 15 and SEQ ID NO: 60 anda heavy chain CDR 3 selected from the group consisting of SEQ ID NO: 56 or SEQ ID NO: 59 and SEQ ID NO: 16, and(b) a second heavy chain comprising a heavy ...

UNIVERSAL BACK NAVIGATION FOR MULTIPLE WINDOWS

Techniques are described herein that are capable of providing universal back navigation for multiple windows. Universal back navigation allows universal back functionality to transition between operating in an in-application context and a cross-application context. In the in-application context, operation of the universal back functionality is restricted to functionality of an application (e.g., a single application) to which user instructions are to be currently directed by default. In the cross-application context, operation of the universal back functionality is not restricted to functionality of the application to which user instructions are to be currently directed by default. 1. A system to provide universal back navigation for multiple computer windows , the system comprising:at least one element comprising at least one of (a) one or more processors or (b) hardware logic/electrical circuitry;a screen; the universal back functionality configured to transition between a first state and a second state while the plurality of computer software applications are displayed simultaneously on the screen,', 'the first state characterized by the universal back functionality operating within an in-application context of a single computer software application of the plurality of computer software applications, the single computer software application being the focus application,', 'the second state characterized by the universal back button operating within a cross-application context between two or more entities, each entity of the two or more entities being an application window or a system user interface surface;, 'the provision logic further configured to provide universal back functionality configured to perform a back operation in response to the universal back functionality being engaged'}, 'provision logic, implemented using the at least one element, configured to display a plurality of computer software applications in a plurality of respective computer windows ...

TETRAVALENT MULTISPECIFIC ANTIBODIES

The present invention relates to novel tetravalent multispecific antibodies, their manufacture and use. 1. A tetravalent multispecific antibody , comprisinga) one core antibody formed by a full length antibody, the full length antibody comprising two Fab fragments specifically binding to a first antigen, andb) two additional Fab fragments, wherein said additional Fab fragments are fused both either at the C-termini or the N-termini of the heavy chains of the core antibody, wherein the additional Fab fragments specifically bind to a second antigen, the Fab fragments specifically binding to the first antigen, or', 'the Fab fragments specifically binding to the second antigen comprise a domain crossover such that the variable heavy chain domain (VH) and the variable light chain domain (VL) are replaced by each other, and, 'i) wherein either'} the Fab fragments specifically binding to the first antigen, or', 'the Fab fragments specifically binding to the second antigen comprise the following amino acid substitutions in the constant light chain domain (CL) and the constant heavy chain domain 1 (CH1):', 'the amino acid at position 124 in the CL domain is substituted by K, R or H (numbering according to Kabat), and', 'the amino acid at position 147 or 213 in the CH1 domain is substituted by E or D (numbering according to Kabat EU index)., 'ii) wherein either'}2. A tetravalent multispecific antibody , comprisinga) one core antibody formed by a full length antibody, the full length antibody comprising two Fab fragments specifically binding to a first antigen and a second antigen, respectively, andb) two additional Fab fragments, wherein said additional Fab fragments are fused both either at the C-termini or the N-termini of the heavy chains of the core antibody, wherein the additional Fab fragment fused to a heavy chain exhibits the same antigen binding specificity than the Fab fragment of the core antibody arranged on said heavy chain, the Fab fragments specifically binding ...

T CELL ACTIVATING BISPECIFIC ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1123-. (canceled)124. An antigen-binding molecule comprising a Folate Receptor 1 (FolR1) antigen-binding moiety that binds to FolR1 , wherein the FolR1 antigen-binding moiety comprises at least one heavy chain complementarity determining region (CDR) comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 16 , SEQ ID NO: 17 , and SEQ ID NO: 18 and at least one light chain CDR comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 32 , SEQ ID NO: 33 , and SEQ ID NO: 34.125. The antigen-binding molecule of claim 124 , wherein the FolR1 antigen-binding moiety comprises:(i) a complementarity-determining region heavy chain 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 16;(ii) a complementarity-determining region heavy chain 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 17;(iii) a complementarity-determining region heavy chain 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 18;(iv) a complementarity-determining region light chain 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 32;(v) a complementarity-determining region light chain 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 33; and(vi) a complementarity-determining region light chain 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 34.126. The antigen-binding molecule of claim 125 , wherein the FolR1 antigen-binding moiety comprises a variable heavy chain ...

ERGONOMIC PHYSICAL INTERACTION ZONE CURSOR MAPPING

Users move their hands in a three dimensional (“3D”) physical interaction zone (“PHIZ”) to control a cursor in a user interface (“UI”) shown on a computer-coupled 2D display such as a television or monitor. The PHIZ is shaped, sized, and positioned relative to the user to ergonomically match the user's natural range of motions so that cursor control is intuitive and comfortable over the entire region on the UI that supports cursor interaction. A motion capture system tracks the user's hand so that the user's 3D motions within the PHIZ can be mapped to the 2D UI. Accordingly, when the user moves his or her hands in the PHIZ, the cursor correspondingly moves on the display. Movement in the z direction (i.e., back and forth) in the PHIZ allows for additional interactions to be performed such as pressing, zooming, 3D manipulations, or other forms of input to the UI. 1. A computer-implemented method for moving a cursor on a two-dimensional (“2D”) display in response to motion of a user's hand , the method comprising the steps of:capturing locations of the user's hand within a monitored physical interaction zone (“PHIZ”), the PHIZ being ergonomically matched to the user's natural range of motions;tracking the locations within the PHIZ to determine motion of the user's hand; andmapping the tracked hand locations from the PHIZ to the display so that motion of the hand in the PHIZ results in a corresponding motion of the cursor on the display.2. The computer-implemented method of further including a step of generating a plurality of tuning parameters claim 1 , the tuning parameters enabling a size claim 1 , shape claim 1 , or location of the PHIZ to be tuned to a given configuration of the user within an area of captured motion.3. The computer-implemented method of in which the configuration of the user is one of standing claim 2 , seated claim 2 , lying down claim 2 , having unconstrained whole arm motion claim 2 , having constrained whole arm motion claim 2 , having ...

Method for manufacturing electrically conductive structures on a carrier material

A method for manufacturing electrically conductive structures, preferably conductive pathway structures using laser beams on a non-conductive carrier (LDS method), wherein a non-conductive carrier material is provided which contains at least one inorganic metal phosphate compound and at least one stabiliser finely distributed or dissolved therein, the carrier material is irradiated in regions by laser beams generating the electrically conductive structures in the irradiated regions.

Antibodies binding to NKG2D

The present invention generally relates to antibodies that bind to NKG2D, including multispecific antigen binding molecules e.g. for activation of T cells and/or NK cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease. 1. An antibody that binds to NKG2D , wherein the antibody comprises a first antigen binding domain , comprising(i) a heavy chain variable region (VH) comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 73, a HCDR 2 selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104 and SEQ ID NO: 105, and a HCDR 3 of SEQ ID NO: 75, and a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 76, a LCDR 2 of SEQ ID NO: 77 and a LCDR 3 of SEQ ID NO: 78;(ii) a VH comprising a HCDR 1 of SEQ ID NO: 65, a HCDR 2 of SEQ ID NO: 66, and a HCDR 3 of SEQ ID NO: 67, and a VL comprising a LCDR 1 of SEQ ID NO: 68, a LCDR 2 of SEQ ID NO: 69 and a LCDR 3 of SEQ ID NO: 70;(iii) a VH comprising a HCDR 1 of SEQ ID NO: 1, a HCDR 2 of SEQ ID NO: 2, and a HCDR 3 of SEQ ID NO: 3, and a VL comprising a LCDR 1 of SEQ ID NO: 4, a LCDR 2 of SEQ ID NO: 5 and a LCDR 3 of SEQ ID NO: 6;(iv) a VH comprising a HCDR 1 of SEQ ID NO: 25, a HCDR 2 of SEQ ID NO: 26, and a HCDR 3 of SEQ ID NO: 27, and a VL comprising a LCDR 1 of SEQ ID NO: 28, a LCDR 2 of SEQ ID NO: 29 and a LCDR 3 of SEQ ID NO: 30;(v) a VH comprising a HCDR 1 of SEQ ID NO: 49, a HCDR 2 of SEQ ID NO: 50, and a HCDR 3 of SEQ ID NO: 51, and a VL comprising a LCDR 1 of SEQ ID NO: 52, a LCDR 2 of SEQ ID NO: 53 and a LCDR 3 of SEQ ID NO: 54;(vi) a VH comprising a HCDR 1 of SEQ ID NO: 57, a HCDR 2 of SEQ ID NO: 58, and a HCDR 3 of SEQ ID NO: 59, and a VL comprising a LCDR 1 of SEQ ID ...

BIVALENT, BISPECIFIC ANTIBODIES

The present invention relates to a host cell for use in the expression of a novel domain exchanged, bivalent, bispecific antibody. 1. A host cell for use in expressing a domain exchanged , bivalent , bispecific antibody , said host cell comprising:vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a first antigen;vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a second antigen, wherein the variable domains VL and VH from the antibody specifically binding to a second antigen are replaced by each other.2. A host cell according to wherein said host cell comprises:a) a vector comprising a nucleic acid molecule encoding the light chain and a vector comprising a nucleic acid molecule encoding the heavy chain, of an antibody specifically binding to a first antigenb) a vector comprising a nucleic acid molecule encoding the light chain and a vector comprising a nucleic acid molecule encoding the heavy chain, of an antibody specifically binding to a second antigen, wherein the variable domains VL and VH are replaced by each other.3. A host cell according to wherein:in the final bispecific antibody, the CH3 domain of one heavy chain meets at an interface with the CH3 domain of the other heavy chain; andwithin said interface, the CH3 domain of one heavy chain is altered so that an amino acid residue is replaced with an amino acid residue having a larger side chain volume thereby generating a protuberance, and the CH3 domain of the other heavy chain is altered so that an amino acid residue is replaced with an amino acid residue having a smaller chain volume thereby generating a cavity wherein said protuberance is positionable.4. A host cell according to claim 3 , wherein the amino acid residue having a larger side chain volume is selected from the group consisting of arginine (R) claim 3 , phenylalanine (F) claim 3 , tyrosine (Y) claim ...

SYSTEM WITH MULTIPLE SIMULTANEOUS SPEECH RECOGNIZERS

A speech recognition system interprets both spoken system commands as well as application commands. Users may speak commands to an open microphone of a computing device that may be interpreted by at least two speech recognizers operating simultaneously. The first speech recognizer interprets operating system commands and the second speech recognizer interprets application commands. The system commands may include at least opening and closing an application and the application commands may include at least a game command or navigation within a menu. A reserve word may be used to identify whether the command is for the operation system or application. A user's cadence may also indicate whether the speech is a global command or application command. A speech recognizer may include a natural language software component located in a remote computing device, such as in the so-called cloud. 1. A method to operate a computing device , the method comprising:receiving, by a first speech recognizer, information that represents a global command from a microphone;receiving, by a second speech recognizer, information that represents an application command from the microphone, the second speech recognizer operates simultaneously with the first speech recognizer; andperforming, by the computing device, a computing operation in response to one of the information that represents the global command and the information that represents the application command.2. The method of claim 1 , wherein the first and second speech recognizers are included in an operating system.3. The method of claim 2 , wherein the computing device includes an intelligent agent claim 2 , and wherein the method further includes providing a voice out claim 2 , by the intelligent agent claim 2 , in response one of the information that represents the global command and the information that represents the application command.4. The method of claim 1 , wherein the global command includes at least one of launching ...

LIQUID-CRYSTALLINE MEDIUM

The present invention relates to a liquid-crystalline medium (LC medium), to the use thereof for electrooptical purposes and to LC displays comprising this medium. 17. The liquid-crystalline medium according to claim 1 , wherein said medium contains:20% to 65% by weight of one or more compounds of formula 1,2% to 15% by weight of one or more compounds of the formula 2,5% to 30% by weight of one or more compounds selected from formulae 3, 4 and 5, and2% to 20% by weight of one or more compounds selected from formulae 6 and 7.18. The liquid-crystalline medium according to claim 1 , wherein said medium contains one or more compounds of each of formula 1 claim 1 , formula 2 claim 1 , and formula 3 claim 1 , and one or more compounds selected from formulae 6 and 7.19. The liquid-crystalline medium according to claim 1 , further comprising one or more additive(s) selected from UV stabilizers claim 1 , dopants and antioxidants.20. The liquid-crystalline medium according to claim 1 , further comprising one or more polymerizable compounds.21. A process for producing a liquid-crystalline medium according to claim 1 , comprising:mixing one or more compounds of formulae 1 to 7 with further mesogenic compounds and optionally with one or more additives and/or at least one polymerizable compound.22. A method of generating an electrooptical effect comprising applying a voltage across a liquid-crystalline medium according to .23. A shutter glass for 3D applications claim 1 , or in TN claim 1 , PS-TN claim 1 , STN claim 1 , ECB claim 1 , OCB claim 1 , IPS claim 1 , PS-IPS claim 1 , FFS claim 1 , PS-FFS or positive-VA displays claim 1 , comprising a liquid-crystalline medium according to .24. An electrooptical liquid-crystal display comprising a liquid-crystalline medium claim 1 , wherein said medium is a medium according to .25. An electrooptical liquid-crystal display according to claim 24 , wherein said display is a TN claim 24 , PS-TN claim 24 , STN claim 24 , ECB claim 24 , OCB ...

LIQUID-CRYSTALLINE MEDIUM

The invention relates to compounds of the formula I 2. The liquid-crystalline medium according to claim 1 , wherein Rin formula I denotes a straight-chain alkyl radical claim 1 , in which claim 1 , in addition claim 1 , one or more CHgroups may be replaced by —CH═CH—.17. The liquid-crystalline medium according to claim 1 , comprising I-30% by weight of compounds of the formula I.18. The liquid-crystalline medium according to claim 1 , additionally comprising one or more UV stabilizers and/or antioxidants.19. The liquid-crystalline medium according to claim 1 , additionally comprising one or more polymerizable compounds.20. A process for the preparation of a liquid-crystalline medium according to claim 1 , comprising mixing one or more compounds of the formula I with at least one further mesogenic compound and optionally with one or more additive(s) and/or one or more polymerizable compounds.21. An electro-optical liquid-crystal display containing a liquid-crystalline medium according to .22. The display according to claim 21 , that is a TN claim 21 , STN claim 21 , TN-TFT claim 21 , OCB claim 21 , IPS claim 21 , PS-IPS claim 21 , FFS claim 21 , HB-FFS or PS-FFS displays.23. Shutter spectacles having 3D effects claim 1 , LC lenses or positive VA displays containing a liquid-crystal medium according to . The present invention relates to a liquid-crystalline medium (LC medium), to the use thereof for electro-optical purposes, and to LC displays containing this medium.Liquid crystals are used principally as dielectrics in display devices, since the optical properties of such substances can be modified by an applied voltage. Electro-optical devices based on liquid crystals are extremely well known to the person skilled in the art and can be based on various effects. Examples of such devices are cells having dynamic scattering, DAP (deformation of aligned phases) cells, guest/host cells, TN cells having a “twisted nematic” structure, STN (“super-twisted nematic”) cells, ...

MONOVALENT ANTIGEN BINDING PROTEINS

The present invention relates to monovalent antigen binding proteins with a CH1-CL domain exchange, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 112-. (canceled)13. A method for the preparation of a monovalent antigen binding protein comprising the steps of i) a modified heavy chain of an antibody which specifically binds to an antigen, wherein the VH domain is replaced by the VL domain of said antibody; and', 'ii) a modified heavy chain of said antibody, wherein the CH1 domain is replaced by the CL domain of said antibody;, 'a) transforming a host cell with vectors comprising nucleic acid molecules encoding a monovalent antigen binding protein, wherein the monovalent antigen binding protein comprises'}b) culturing the host cell under conditions that allow synthesis of said monovalent antigen binding protein molecule; andc) recovering said monovalent antigen binding protein molecule from said culture;wherein the preparation is free of detectable homodimers.1416-. (canceled)17. The method according to claim 13 , wherein the monovalent antigen binding protein comprises:the modified heavy chain of the antibody of i) comprises a CH3 domain;the modified heavy chain of antibody of ii) comprises a CH3 domain; whereinthe CH3 domain of the modified heavy chain of the antibody of i) and the CH3 domain of the modified heavy chain of the antibody of ii) each meet at an interface which comprises an original interface between the antibody CH3 domains; a CH3 domain of one heavy chain is altered, so that within the original interface the CH3 domain of one heavy chain that meets the original interface of the CH3 domain of the other heavy chain within the monovalent antigen binding protein, an amino acid residue is replaced with an amino acid residue having a larger side chain volume, thereby generating a protuberance within the interface of the CH3 domain of one heavy chain which is positionable in a cavity within the ...

Verfahren und Wirbelströmungsmessgerät Zur Bestimmung des Massenstromverhältnisse einermhrphasigen Strömung

A vortex flow measuring device as well as a method for determining by means of a vortex, flow measuring a device, which has a bluff body protruding into the flowing medium and a vortex sensor, the mass flow ratio (x) of an at least at times two- or multiphase medium flowing in a measuring tube and having a gaseous first phase flowing with a first mass flow rate {dot over (m)}and a liquid second phase flowing with a second mass flow rate {dot over (m)}. The gaseous phase has a first density (ρ), which differs from a second density (ρ) of the liquid phase, comprising: producing Kármán vortices in the flowing medium at least in the region of the vortex sensor by means of the bluff body, the vortices are shed from the bluff body with a vortex shedding frequency (f) dependent on an instantaneous flow velocity of the flowing medium; registering by means of the vortex sensor periodic pressure fluctuations caused by the Kármán vortex in the flowing medium for producing a sensor signal corresponding to the pressure fluctuations; selecting from the sensor signal a wanted signal component, which has a frequency band, especially a narrow frequency band, containing the vortex shedding frequency, especially with a relative bandwidth less than 50% of the instantaneous vortex shedding frequency, wherein preferably the instantaneous vortex shedding frequency represents the center frequency of the frequency bandwidth; and applying the wanted signal component (M) for determining a mass flow ratio (x) of the flowing medium, wherein the mass flow ratio (x) is defined as a ratio of the first mass flow {dot over (m)}to a total mass flow, with which the medium flows, especially according to a formula: 119-. (canceled)21. The method as claimed in claim 20 , further comprising the steps of:ascertaining at least one fluctuation value of the wanted signal component over a time interval, especially a time interval extending over a number of periods of the pressure fluctuations of the flow, ...

BISPECIFIC, TETRAVALENT ANTIGEN BINDING PROTEINS

The present invention relates to bispecific, tetravalent antigen binding proteins, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 112-. (canceled)14. The one or more nucleic acid molecules of claim 13 , whereini) the CH3 domain of one of the first or second heavy chains is altered,so that an amino acid residue in the CH3 domain of said first or second heavy chain is replaced with an amino acid residue having a larger side chain volume, thereby generating a protuberance which is positionable in a cavity within the interface of the CH3 domain of the other heavy chainandii) the CH3 domain of the other heavy chain is altered,so that an amino acid residue in the CH3 domain of the other heavy chain is replaced with an amino acid residue having a smaller side chain volume, thereby generating a cavity within which a protuberance as set forth in i) above is positionable.15. The one or more nucleic acid molecules of claim 14 , wherein said amino acid residue having a larger side chain volume is selected from the group consisting of arginine (R) claim 14 , phenylalanine (F) claim 14 , tyrosine (Y) claim 14 , tryptophan (W) and said amino acid residue having a smaller side chain volume is selected from the group consisting of alanine (A) claim 14 , serine (S) claim 14 , threonine (T) claim 14 , valine (V).16. The one or more nucleic acid molecules of claim 15 , whereinboth CH3 domains are further altered by the introduction of cysteine (C) as amino acid in the corresponding positions of each CH3 domain such that a disulfide bridge between both CH3 domains can be formed.17. The one or more nucleic acid molecules of claim 13 , wherein the fusion of the first heavy chain and the fusion of the second heavy chain are by linkage with a peptide linker.18. The one or more nucleic acid molecules of claim 17 , wherein the peptide linker comprises (GS)G claim 17 , wherein x=3; n=3 claim 17 , 4 claim 17 , 5 claim 17 , or 6; and m=0 ...

Aromatic compounds

The present invention relates to aromatic compounds suitable for preparation of asymmetric polydentate ligands. The present invention further describes a process for preparing asymmetric polydentate ligands and metal complexes comprising these ligands which are suitable for use as emitters in organic electroluminescent devices.

BISPECIFIC ANTI-VEGF/ANTI-ANG-2 ANTIBODIES

The present invention relates to bispecific antibodies against human VEGF and against human ANG-2, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A method of treatment of a patient suffering from a disease or disorder which is cancer or a vascular disease , said method comprising the step of administering a bispecific antibody to a patient in the need of such treatment , said bispecific antibody being one that binds specifically to human vascular endothelial growth factor (VEGF) and human angiopoietin-2 (ANG-2) and comprises a first antigen-binding site that specifically binds to human VEGF and a second antigen-binding site that specifically binds to human ANG-2 , wherein:i) said antigen-binding sites each comprise an antibody heavy chain variable domain and an antibody light chain variable domain; a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 9, SEQ ID NO: 17, and SEQ ID NO: 94;', 'a CDR2 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 18, and SEQ ID NO: 95;', 'and a CDR1 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:3, SEQ ID NO: 11, SEQ ID NO: 19, and SEQ ID NO: 96, and', 'in the light chain variable domain:', 'a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, and SEQ ID NO: 97,', 'a CDR2 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:5, SEQ ID NO: 13, SEQ ID NO: 21, and SEQ ID NO: 98; and', 'a CDR1 region having an amino acid sequence selected from the group consisting of: SEQ ID NO:6, SEQ ID NO: 14, SEQ ID NO: 22, and SEQ ID NO: 99; and, 'ii) said first antigen-binding site comprises in the heavy chain variable domain a CDR3 region having an amino acid sequence selected from the group consisting of: SEQ ID NO: 25, SEQ ID ...

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A T cell activating bispecific antigen binding molecule comprising(i) a first antigen binding moiety which is a Fab molecule capable of specific binding to CD3, comprising at least one heavy chain complementarity determining region (CDR) selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 and at least one light chain CDR selected from the group of SEQ ID NO: 8, SEQ ID NO: 9 and SEQ ID NO: 10;(ii) a second antigen binding moiety which is a Fab molecule capable of specific binding to a target cell antigen.2. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first antigen binding moiety comprises a heavy chain variable region comprising an amino acid sequence that is at least about 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% identical to an amino acid sequence selected from the group of: SEQ ID NO: 3 claim 1 , SEQ ID NO: 32 and SEQ ID NO: 33 and a light chain variable region comprising an amino acid sequence that is at least about 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% identical to the amino acid sequence selected from the group of: SEQ ID NO: 7 and SEQ ID NO: 31.3. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first antigen binding moiety comprises a heavy chain variable region comprising an amino acid sequence that is at least about 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , ...

ANTIBODIES BINDING TO GPRC5D

The present invention generally relates to antibodies that bind to GPRC5D, including bispecific antigen binding molecules e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease. 1. An antibody that binds to GPRC5D , wherein the antibody comprises a heavy chain variable region and a light chain variable region selected from:(i) a heavy chain variable region (VH) comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 83, a HCDR 2 of SEQ ID NO: 84, and a HCDR 3 of SEQ ID NO: 86, and a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 87, a LCDR 2 of SEQ ID NO: 88 and a LCDR 3 of SEQ ID NO: 89;(ii) a heavy chain variable region (VH) comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 83, a HCDR 2 of SEQ ID NO: 85, and a HCDR 3 of SEQ ID NO: 86, and a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 87, a LCDR 2 of SEQ ID NO: 88 and a LCDR 3 of SEQ ID NO: 89;(iii) a heavy chain variable region (VH) comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 90, a HCDR 2 of SEQ ID NO: 91, and a HCDR 3 of SEQ ID NO: 93, and a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 94, a LCDR 2 of SEQ ID NO: 95 and a LCDR 3 of SEQ ID NO: 97;(iv) a heavy chain variable region (VH) comprising a heavy chain complementary determining region (HCDR) 1 of SEQ ID NO: 90, a HCDR 2 of SEQ ID NO: 91, and a HCDR 3 of SEQ ID NO: 93, and a light chain variable region (VL) comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 94, a LCDR 2 of SEQ ID NO ...

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH AN ANTI-BCL-2 ACTIVE AGENT

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and an anti-Bcl-2 active agent. 1. A composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent.2. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.63. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.4. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).5. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.6. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is selected from the group consisting of Oblimersen claim 1 , SPC-2996 claim 1 , RTA-402 claim 1 , Gossypol claim 1 , AT-101 claim 1 , Obatoclax mesylate claim 1 , A-371191 claim 1 , A-385358 claim 1 , A-438744 claim 1 , ABT-737 claim 1 , AT-101 claim 1 , BL-11 claim 1 , BL-193 claim 1 , GX-15-003 claim 1 , 2-Methoxyantimycin A3 claim 1 , HA-14-1 claim 1 , KF-67544 claim 1 , Purpurogallin claim 1 , TP-TW-37 claim 1 , YC-137 and Z-24.7. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is ...

Combination therapy of PD-1-targeted IL-2 variant immunocytokines and antibodies against human PD-L1

The present invention relates to the combination therapy of specific PD-1-targeted IL-2 variant immunocytokines with specific antibodies which bind human PD-L 1. A therapeutic method comprising administering to a subject a combination therapy comprising (a) a PD-1-targeted IL-2 variant immunocytokine in combination with (b) an antibody which binds to human PD-L1 , i) a heavy chain variable domain VH of SEQ ID NO:5 and a light chain variable domain VL of SEQ ID NO:6, and the polypeptide sequence of SEQ ID NO:2, or', 'ii) a polypeptide sequence of SEQ ID NO:7 or SEQ ID NO:8 or SEQ ID NO:9, or', 'iii) the polypeptide sequences of SEQ ID NO:7, and SEQ ID NO:8 and SEQ ID NO:9, or', 'iv) the polypeptide sequences of SEQ ID NO:12, and SEQ ID NO:13 and SEQ ID NO:14,, 'wherein the PD-1-targeted IL-2 variant immunocytokine comprises i) a heavy chain variable domain VH of SEQ ID NO:15 and a light chain variable domain VL of SEQ ID NO:16, or', 'ii) a heavy chain variable domain VH of SEQ ID NO:19 and a light chain variable domain VL of SEQ ID NO:20., 'and wherein the antibody which binds to human PD-L1 comprises2. The method of claim 1 , wherein the combination therapy is for treating a cancer.3. The method of claim 2 , wherein the cancer is selected from the group consisting of breast cancer claim 2 , lung cancer claim 2 , colon cancer claim 2 , ovarian cancer claim 2 , melanoma cancer claim 2 , bladder cancer claim 2 , renal cancer claim 2 , kidney cancer claim 2 , liver cancer claim 2 , head and neck cancer claim 2 , colorectal cancer claim 2 , melanoma claim 2 , pancreatic cancer claim 2 , gastric carcinoma cancer claim 2 , esophageal cancer claim 2 , mesothelioma claim 2 , prostate cancer claim 2 , leukemia claim 2 , and lymphomas claim 2 , myelomas.4. The method of claim 1 , wherein the combination therapy is for the prevention or treatment of metastasis.5. The method of claim 1 , wherein the combination therapy is for treating or delaying progression of an immune related ...