MAMMALIAN RECEPTOR PROTEINS; RELATED REAGENTS AND METHODS

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 1. A method of treating a human subject experiencing a physiological disorder comprising administering an effective amount of an agonist or antagonist of DCRS5 (SEQ ID NOs:1 or 2) or of p19 (SEQ ID NOs:5 or 6) , wherein the disorder comprises:a) rheumatoid arthritis;b) asthma or allergy;c) chronic obstructive pulmonary disorder (COPD);d) an interstitial lung disorder;e) an inflammatory bowel disorder (IBD); orf) an inflammatory skin disorder.2. The method of claim 1 , wherein the skin disorder is:a) psoriasis; orb) atopic dermatitis.3. The method of claim 1 , wherein the IBD is:a) Crohn's disease; orb) ulcerative colitis.4. The method of claim 1 , wherein the interstitial lung disorder is:a) idiopathic pulmonary fibrosis;b) eosinophilic granuloma; orc) hypersensitivity pneumonitis.5. The method of claim 1 , wherein the antagonist comprises a binding composition derived from the antigen binding site of an antibody that specifically binds to:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).6. The method of claim 5 , wherein the binding composition comprises:a) a polyclonal antibody;b) a monoclonal antibody;c) a humanized antibody; or{'sub': '2', 'd) an Fab, Fv, or F(ab′)fragment.'}7. The method of claim 1 , wherein the agonist comprises:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).8. The method of claim 1 , wherein the agonist or antagonist comprises a nucleic acid.9. The method of claim 8 , wherein the antagonist comprises:a) an antisense nucleic acid; orb) an RNA interference nucleic acid.10. A method of diagnosing a physiological disorder comprising contacting a binding composition that specifically binds to DCRS5 (SEQ ID NOs:1 or 2) claim 8 , or to p19 (SEQ ID NOs:5 or 6) claim 8 , to a sample derived ...

MAMMALIAN CYTOKINES; RELATED REAGENTS

Purified genes encoding a cytokine or composite cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided. 1. An isolated or recombinant polynucleotide encoding an antigenic polypeptide comprising at least 17 contiguous amino acids from the mature polypeptide from SEQ ID NO: 2 , 4 , 6 , or 8.2. The polynucleotide of claim 1 , encoding a mature polypeptide from SEQ ID NO: 2 claim 1 , 4 claim 1 , 6 claim 1 , or 8.3. The polynucleotide of claim 1 , which hybridizes at 55° C. claim 1 , less than 500 mM salt claim 1 , and 50% formamide to the coding portions of SEQ ID NO: 1 claim 1 , 3 claim 1 , 5 claim 1 , or 7.4. The polynucleotide of claim 3 , comprising at least 35 contiguous nucleotides of the coding portion of SEQ ID NO: 1 claim 3 , 3 claim 3 , 5 claim 3 , or 7.5. An expression vector comprising the polynucleotide of .6. A host cell containing the expression vector of claim 5 , including a eukaryotic cell.7. A method of making an antigenic polypeptide comprising expressing a recombinant polynucleotide of .85. A method for forming a duplex with a polynucleotide of claim 1 , comprising contacting said polynucleotide with a probe that hybridizes claim 1 , under stringent conditions claim 1 , to at least 25 contiguous nucleotides of the coding portion of SEQ ID NO: 1 claim 1 , 3 claim 1 , 5 claim 1 , or 7; thereby forming said duplex.9. A kit for the detection of a polynucleotide of claim 1 , comprising a polynucleotide that hybridizes claim 1 , under stringent hybridization conditions claim 1 , to at least 17 contiguous nucleotides of a polynucleotide of .10. The kit of claim 9 , wherein said probe is detectably labeled.11. A binding compound comprising an antibody binding site which specifically binds to at least 17 contiguous amino acids from SEQ ID NO: 2 claim 9 , 4 claim 9 , 6 claim 9 , or 8.12. The ...

MAMMALIAN RECEPTOR PROTEINS; RELATED REAGENTS AND METHODS

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 123-. (canceled)24. A recombinant polypeptide comprising a sequence having at least 95% sequence identity with residues 24-629 of SEQ ID NO:2.25. The polypeptide of claim 24 , wherein the polypeptide claim 24 , when combined with IL-12Rβ1 claim 24 , is able to form a functional receptor complex for p40/IL-B30.26. The polypeptide of claim 24 , wherein the polypeptide comprises the sequence of residues 24-629 of SEQ ID NO:2.27. The polypeptide of claim 26 , wherein the polypeptide consists of the sequence of residues 24-629 of SEQ ID NO:2.28. A recombinant polynucleotide encoding the polypeptide of .29. The polynucleotide of comprising a sequence having at least 95% sequence identity with residues 188-2005 of SEQ ID NO:1.30. The polynucleotide of claim 29 , wherein the polypeptide claim 29 , when combined with IL-12Rβ1 claim 29 , is able to form a functional receptor complex for p40/IL-B30.31. A composition comprising:{'claim-ref': {'@idref': 'CLM-00026', 'claim 26'}, 'a) the polypeptide of ; and'}b) IL-12Rβ1.32. An antibody claim 27 , or antigen binding fragment thereof claim 27 , that specifically binds to the polypeptide of .33. An antibody fragment of claim 32 , wherein the fragment is an Fv claim 32 , Fab or Fab2 fragment.34. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00032', 'claim 32'}, 'a) the antibody, or antigen binding fragment thereof, of ; and'}b) a pharmaceutically acceptable carrier.35. An antibody raised against the polypeptide of .36. A method of raising an antibody comprising:{'claim-ref': [{'@idref': 'CLM-00025', 'claim 25'}, {'@idref': 'CLM-00025', 'claim 25'}], 'a) injecting an animal with the polypeptide of , or exposing of a library of antibodies in phage ...

Pathogenic TH17 Cells; related reagents and methods

Methods and compositions are provided for the treatment of immune disorders, such as autoimmune diseases, or cancers, involving combination therapy with agents that inhibit the development or maintenance of Th17 cells. Treatment regimens are provided in which an antagonist of a pro-inflammatory cytokine is administered for a time sufficient to alleviate signs and symptoms of an acute phase flare-up of the autoimmune disease, or cancer, and treatment with an antagonist of IL-23 is continued for a longer time to prevent recurrence of the acute event. Antagonists of PGE2 and CD161 are also disclosed for use in treatment of autoimmune, inflammatory and proliferative disorders. 138-. (canceled)39. A method of specifically detecting pathogenic Th17 cells within a population of cells , comprising:a) adding an antibody, or antigen binding fragment thereof, that specifically binds to IL-23R to the population of cells;b) adding an antibody, or antigen binding fragment thereof, that specifically binds to CD161 to the population of cells;c) allowing the antibodies or fragments to bind to the cells; andd) detecting cells that are bound by both antibodies or fragments, which cells are pathogenic Th17 cells.40. The method of claim 39 , wherein the antibody claim 39 , or antigen binding fragment thereof claim 39 , that binds to IL-23R and the antibody claim 39 , or antigen binding fragment thereof claim 39 , that binds to CD161 are separate antibodies or fragments.41. The method of claim 39 , wherein the antibody claim 39 , or antigen binding fragment thereof claim 39 , that binds to IL-23R and to CD161 is a single bispecific antibody molecule claim 39 , or antigen binding fragment thereof.42. The method of claim 40 , wherein the antibody claim 40 , or antigen binding fragment thereof claim 40 , that binds to IL-23R and the antibody claim 40 , or antigen binding fragment thereof claim 40 , that binds to CD161 are both labeled with fluorescent reagents.43. The method of claim 41 , ...

METHODS OF TREATMENT USING AN ANTI IL B50 ANTIBODY

Nucleic acids encoding mammalian cytokine receptor, e.g., for cytokine IL-B50, purified proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 13.-. (canceled)4. A method of modulating physiology or development of an IL-7Rα or Rδ2 expressing cell comprising contacting said cell to an exogenous agonist or antagonist of a mammalian IL-B50.5. The method of claim 4 , wherein: 1) an antibody which neutralizes said mammalian IL-B50;', '2) a mutein of said IL-B50; or', '3) an antibody which binds to IL-7Rα or Rδ2 or a complex comprising both;, 'A) said antagonist is 1) proliferation;', '2) lymphoid or dendritic lineage cell development;', '3) antigen presentation; or', '4) production of inflammatory mediators, including cytokines, chemokines, or adhesion molecules; or, 'B) said physiology is selected fromC) said cell is a hematopoietic cell.6. The method of claim 4 , wherein:a) said antagonist is an antibody and said physiology is hematopoietic cell proliferation;b) said agonist is IL-B50 and said physiology is hematopoietic cell differentiation; orc) said physiology is antigen presentation.7. The method of claim 4 , wherein said modulating is blocking claim 4 , and said physiology is lymphoid lineage cell proliferation.8. A method of modulating a signal to a cell mediated by IL-B50 comprising contacting said cell to an administered agonist or antagonist of IL-B50.9. The method of claim 8 , wherein said modulating is inhibiting claim 8 , and said signal is a proliferation signal.10. The method of claim 9 , wherein:a) said antagonist is a neutralizing antibody to IL-7Rα or the Rδ2 subunit or a complex comprising said subunits;b) said agonist or antagonist is administered in combination with another antagonist or agonist of IL-B50; orc) said agonist or antagonist is administered in combination with a growth factor, cytokine, chemokine, or ...

METHODS FOR MODULATING IL-33 ACTIVITY

Provided herein are methods of modulating IL-33 activity, e.g., for the purpose of treating immune diseases and conditions, as well as methods of screening for compounds capable antagonizing IL-33 signaling. 1. A method of modulating an immune disorder or condition , comprising inhibiting IL-33 signal transduction through ST2 and IL-1RAcP by administering to a subject in need thereof an effective amount of:a) an antagonist of IL-33 binding to a complex of ST2 and IL-1RAcP; orb) an antagonist of IL-1RAcP binding to a complex of IL-33 and ST2.2. The method of claim 1 , wherein the immune disorder or condition is selected from the group consisting of an innate response claim 1 , asthma claim 1 , an allergy claim 1 , multiple sclerosis claim 1 , inflammatory bowel disorder claim 1 , arthritis claim 1 , an infection claim 1 , cancer claim 1 , and a tumor.3. The method of claim 2 , wherein the infection is selected from the group consisting of an intracellular pathogen claim 2 , a bacterium claim 2 , a parasite and a virus.4LeishmaniaMycobacteriumListeriaToxoplasmaSchistosoma. The method of claim 3 , wherein the infection is an intracellular pathogen selected from the group consisting of sp. claim 3 , sp. claim 3 , sp. claim 3 , sp. claim 3 , sp.5. The method of claim 1 , wherein the immune disorder or condition comprises:{'sub': 'H', 'a) a T1-type response; or'}{'sub': 'H', 'b) a T2-type response.'}6. The method of claim 2 , wherein the arthritis is selected from the group consisting of rheumatoid arthritis claim 2 , osteoarthritis claim 2 , and psoriatic arthritis.7. The method of claim 1 , wherein the antagonist comprises an antibody or a fragment thereof that specifically binds to:a) IL-33;b) IL-1RAcP;c) ST2;d) a complex of ST2 and IL-1RAcP;e) a complex of IL-33 and ST2; orf) a complex of IL-33, ST2 and IL-1RAcP.8. The method of claim 7 , wherein the antibody or fragment thereof does not bind to ST2 alone and does not bind to IL-33 alone.9. The method of claim 7 , ...

Mammalian Receptor Proteins; Related Reagents and Methods

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 1. A method of treating a human subject experiencing a physiological disorder comprising administering an effective amount of an agonist or antagonist of DCRS5 (SEQ ID NOs:1 or 2) or of p19 (SEQ ID NOs:5 or 6) , wherein the disorder comprises:a) rheumatoid arthritis;b) asthma or allergy;c) chronic obstructive pulmonary disorder (COPD);d) an interstitial lung disorder;e) an inflammatory bowel disorder (IBD); orf) an inflammatory skin disorder.2. The method of claim 1 , wherein the skin disorder is:a) psoriasis; orb) atopic dermatitis.3. The method of claim 1 , wherein the IBD is:a) Crohn's disease; orb) ulcerative colitis.4. The method of claim 1 , wherein the interstitial lung disorder is:a) idiopathic pulmonary fibrosis;b) eosinophilic granuloma; orc) hypersensitivity pneumonitis.5. The method of claim 1 , wherein the antagonist comprises a binding composition derived from the antigen binding site of an antibody that specifically binds to:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).6. The method of claim 5 , wherein the binding composition comprises:a) a polyclonal antibody;b) a monoclonal antibody;c) a humanized antibody; or{'sub': '2', 'd) an Fab, Fv, or F(ab′)fragment.'}7. The method of claim 1 , wherein the agonist comprises:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).8. The method of claim 1 , wherein the agonist or antagonist comprises a nucleic acid.9. The method of claim 8 , wherein the antagonist comprises:a) an antisense nucleic acid; orb) an RNA interference nucleic acid.10. A method of diagnosing a physiological disorder comprising contacting a binding composition that specifically binds to DCRS5 (SEQ ID NOs:1 or 2) claim 8 , or to p19 (SEQ ID NOs:5 or 6) claim 8 , to a sample derived ...

Combination therapy for treatment of immune disorders

Methods and compositions are provided for the treatment of immune disorders, such as autoimmune diseases, or cancers, involving combination therapy with agents that inhibit the development or maintenance of Th17 cells. Treatment regimens are provided in which an antagonist of a pro-inflammatory cytokine is administered for a time sufficient to alleviate signs and symptoms of an acute phase flare-up of the autoimmune disease, or cancer, and treatment with an antagonist of IL-23 is continued for a longer time to prevent recurrence of the acute event. Antagonists of PGE2 and CD161 are also disclosed for use in treatment of autoimmune, inflammatory and proliferative disorders.

USE OF IL-23 AND IL-17 ANTAGONISTS TO TREAT AUTOIMMUNE OCULAR INFLAMMATORY DISEASE

Novel methods and drug products for treating autoimmune ocular inflammatory disease are disclosed, which involve administration of agents that antagonize one or both of IL-17 and IL-23 activity. 1. A method of treating a patient with an autoimmune ocular inflammatory disease (AOID) , comprising administering to the patient an IL-17 antagonist , wherein the AOID is uveitis and the IL-17 antagonist is a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-17.2. The method of claim 1 , wherein the patient has been diagnosed as having an ocular inflammation of putative autoimmune etiology.3. The method of claim 1 , wherein a specified dose of the IL-17 antagonist is administered at a specified interval during a first treatment period.4. The method of claim 3 , wherein the first treatment period ends after disappearance of one or more symptoms of the AOID.5. The method of claim 4 , wherein the first treatment period ends within 30 days after disappearance of all symptoms of the AOID.6. The method of claim 4 , wherein the dose of the IL-17 antagonist administered is gradually reduced during a second treatment period that begins upon the end of the first treatment period.7. The method of claim 6 , wherein the duration of the second treatment period is at least one year.8. The method of claim 3 , further comprising administering an IL-23 antagonist to the patient during the first treatment period claim 3 , wherein the IL-23 antagonist is a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-23p19.9. The method of claim 8 , wherein a specified dose of the IL-23 antagonist is administered at a specified interval during the first treatment period.10. The method of claim 9 , wherein the first treatment period ends after disappearance of one or more symptoms of the AOID.11. The method of claim 9 , wherein the first treatment period ends within 30 days after disappearance of all ...

Use of Cytokine Expression to Predict Skin Inflammation; Methods of Treatment

Provided are methods for diagnosing the propensity of a subject to develop skin inflammation, in particular, psoriasis. Also provided are methods of treatment with antagonists of IL-17, IL-19, and/or IL-23. 1. A method of evaluating the propensity of a subject to develop an inflammatory skin disorder comprising:a) obtaining a sample of skin from the subject; andb) quantifying the level of IL-17 or IL-19 expression in the sample.2. The method of claim 1 , wherein the IL-17 or IL-19 expression is mRNA expression.3. The method of claim 1 , wherein the level of IL-17 or IL-19 expression is quantified by real-time PCR.4. The method of claim 1 , wherein the inflammatory skin disorder is cutaneous inflammation.5. The method of claim 4 , wherein the cutaneous inflammation is psoriasis.6. The method of claim 1 , wherein the skin sample is from both lesional and non-lesional psoriatic skin.7. The method of claim 6 , wherein the level of IL-17 expression in the skin sample is an average value between 5 and 20 fold higher than normal skin.8. The method of claim 6 , wherein the level of IL-19 expression in the skin sample is an average value of between 5 and 130 fold higher than normal skin.9. The method of claim 1 , wherein the subject has:a) a family history of psoriasis; orb) previously presented psoriatic symptoms.10. The method of claim 1 , wherein the subject is a human.11. A method of preventing skin inflammation comprising administering to a subject exhibiting a propensity to develop skin inflammation:a) an antagonist of IL-17;b) an antagonist of IL-23;c) an antagonist of IL-19; orc) an antagonist of at least two cytokines selected from the group consisting of IL-17, IL-19, and IL-23.12. The method of claim 11 , wherein the skin inflammation is cutaneous inflammation.13. The method of claim 11 , wherein the cutaneous inflammation is psoriasis.14. The method of claim 11 , wherein the subject expresses an average value of at least 5 fold higher IL-17 expression in a non- ...

MAMMALIAN CYTOKINES; RECEPTORS; RELATED REAGENTS AND METHODS

Nucleic acids encoding mammalian cytokine receptor, e.g., for cytokine IL-B50, purified proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 2. The method of claim 1 , wherein:a) said mammalian IL-B50 is primate IL-B50;b) said complex formation results in signal transduction, STAT activation, or TARC, PARC or MDC expression;c) said receptor is on a cell;d) said receptor comprises both IL-7Rα and Rδ2 subunit;e) said complex formation results in a physiological change in the cell expressing said receptor;f) said contacting is in combination with a proliferative agent, cytokine, or chemokine; org) said contacting allows quantitative detection of said ligand.3. The method of claim 2 , wherein said receptor is on a hematopoietic cell claim 2 , including a lymphoid lineage cell claim 2 , myeloid claim 2 , or dendritic cell.4. A method of modulating physiology or development of an IL-7Rα or Rδ2 expressing cell comprising contacting said cell to an exogenous agonist or antagonist of a mammalian IL-B50.5. The method of claim 4 , wherein: 1) an antibody which neutralizes said mammalian IL-B50;', '2) a mutein of said IL-B50; or', '3) an antibody which binds to IL-7Rα or Rδ2 or a complex comprising both;, 'A) said antagonist is 1) proliferation;', '2) lymphoid or dendritic lineage cell development;', '3) antigen presentation; or', '4) production of inflammatory mediators, including cytokines, chemokines, or adhesion molecules; or, 'B) said physiology is selected fromC) said cell is a hematopoietic cell.6. The method of claim 4 , wherein:a) said antagonist is an antibody and said physiology is hematopoietic cell proliferation;b) said agonist is IL-B50 and said physiology is hematopoietic cell differentiation; orc) said physiology is antigen presentation.7. The method of claim 4 , wherein said modulating is blocking claim 4 , and said physiology ...

METHODS FOR MODULATING IL-33 ACTIVITY

Provided herein are methods of modulating IL-33 activity, e.g., for the purpose of treating immune diseases and conditions, as well as methods of screening for compounds capable antagonizing IL-33 signaling. 1. A method of modulating an immune disorder or condition , comprising inhibiting IL-33 signal transduction through ST2 and IL-1RAcP by administering to a subject in need thereof an effective amount of:a) an antagonist of IL-33 binding to a complex of ST2 and IL-1RAcP; orb) an antagonist of IL-1RAcP binding to a complex of IL-33 and ST2.2. The method of claim 1 , wherein the immune disorder or condition is selected from the group consisting of an innate response claim 1 , asthma claim 1 , an allergy claim 1 , multiple sclerosis claim 1 , inflammatory bowel disorder claim 1 , arthritis claim 1 , an infection claim 1 , cancer claim 1 , and a tumor.3. The method of claim 2 , wherein the infection is selected from the group consisting of an intracellular pathogen claim 2 , a bacterium claim 2 , a parasite and a virus.4LeishmaniaMycobacteriumListeriaToxoplasmaSchistosoma. The method of claim 3 , wherein the infection is an intracellular pathogen selected from the group consisting of sp. claim 3 , sp. claim 3 , sp. claim 3 , sp. claim 3 , sp.5. The method of claim 1 , wherein the immune disorder or condition comprises:a) a TH1-type response; orb) a TH2-type response.6. The method of claim 2 , wherein the arthritis is selected from the group consisting of rheumatoid arthritis claim 2 , osteoarthritis claim 2 , and psoriatic arthritis.7. The method of claim 1 , wherein the antagonist comprises an antibody or a fragment thereof that specifically binds to:a) IL-33;b) IL-1RAcP;c) ST2;d) a complex of ST2 and IL-1RAcP;e) a complex of IL-33 and ST2; orf) a complex of IL-33, ST2 and IL-1RAcP.8. The method of claim 7 , wherein the antibody or fragment thereof does not bind to ST2 alone and does not bind to IL-33 alone.9. The method of claim 7 , wherein the antibody or fragment ...

PD1 AND/OR LAG3 BINDERS

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided. 1. A LAG3 binder comprising an immunoglobulin single variable domain (ISVD) that binds to LAG3 comprising{'smallcaps': 'GRTFSDYVMG', 'a CDR1 comprising the amino acid sequence (SEQ ID NO: 65) or DYVMG (amino acids 6-10 of SEQ ID NO: 65);'}{'smallcaps': AISESGGRTHYADSVKG', 'AISESGGRTH, 'a CDR2 comprising the amino acid sequence (SEQ ID NO: 66) or (amino acids 1-10 of SEQ ID NO: 66); and'}{'smallcaps': 'TLLWWTSEYAPIKANDYDY', 'a CDR3 comprising the amino acid sequence (SEQ ID NO: 67 wherein the LAG3 binder comprises binds human LAG3 and wherein the ISVD further comprises a substitution of the amino acids at positions 11 and 89 with amino acids V and L, respectively, wherein the numbering is according to Kabat.'}3. The LAG3 binder of or , wherein the LAG3 binder is linked to an albumin binder comprising an ISVD that binds human albumin.4. The binder of wherein the albumin binder has a C-terminal extender comprising alanine.5. An injection device that comprises the LAG3 binder of any one of - claim 3 , optionally in association with a further therapeutic agent.6. A vessel that comprises the LAG3 binder of any one of - claim 3 , optionally in association with a further therapeutic agent.7. A polynucleotide encoding the binder of any one of -.8. A vector comprising the polynucleotide of .9. A host cell comprising the polynucleotide of or a vector comprising the polynucleotide of .10. A method for making a LAG3 binder of any one of - claim 7 , comprising introducing a polynucleotide encoding the binder into a host cell and culturing the host cell in a ...

METHODS OF MODULATING CYTOKINE ACTIVITY; RELATED REAGENTS

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, including tumors and cancer. Also provided are methods of administering agonists or antagonists of IL-33 and IL-33 receptor. 1. A method of modulating an immune disorder or condition , comprising administering an effective amount of an agonist or antagonist of IL-33 of IL-33 Receptor complex (IL-33R).2. The method of claim 1 , wherein the disorder or condition comprises:a) innate response;b) asthma or allergy;c) multiple sclerosis;d) an inflammatory bowel disorder;e) arthritis;f) infection;g) a cancer or tumor.3. The method of claim 2 , wherein the infection comprises:a) an intracellular pathogen;b) a bacterium;c) a parasite; ord) a virus.4. The method of claim 3 , wherein the intracellular pathogen is:{'i': 'Leishmania', 'a) sp.;'}{'i': 'Mycobacterium', 'b) sp.;'}{'i': 'Listeria', 'c) sp.;'}{'i': 'Toxoplasma', 'd) sp.;'}{'i': 'Schistosoma', 'e) ; or'}f) a respiratory virus;5. The method of claim 1 , wherein the immune disorder or conditions comprises:a) TH1-type response; orb) TH2-type response.6. The method of claim 5 , wherein the TH2-type response comprises an early event in TH2-type response.7. The method of claim 1 , wherein the arthritis comprises:a) rheumatoid arthritis;b) osteoarthritis; orc) psoriatic arthritis.8. The method of claim 1 , wherein the agonist comprises:a) IL-33 or;b) a nucleic acid.9. The method of claim 8 , wherein the nucleic acid encodes IL-33.10. The method of claim 1 , wherein the antagonist comprises a binding composition from an antibody that specifically binds:a) IL-33;b) an IL-33R complex; orc) a complex of IL-33 and IL-33R.11. The method of claim 10 , wherein the binding composition from an antibody comprises:a) a polyclonal antibody;b) a monoclonal antibody;c) a humanized antibody, or a fragment thereof;{'sub': '2', 'd) an Fab, Fv, or F(ab′)fragment;'}e) a peptide mimetic of an antibody; orf) a detectable ...

USE OF IL-23 ANTAGONISTS FOR TREATMENT OF INFECTION

Methods and compositions comprising antagonists of IL-23 are provided for the treatment of infections, such as chronic bacterial, viral and fungal infections. 1. A method of treating a subject having a chronic infection selected from the group consisting of a viral infection , a fungal infection and a bacterial infection , comprising administering an effective amount of an antagonist of IL-23.2. (canceled)3. The method of wherein the chronic infection is a fungal infection.4. The method of claim 3 , wherein the fungal infection is selected from the group consisting of candidiasis claim 3 , aspergillosis claim 3 , cryptococcosis and onychomycosis.59-. (canceled)10. The method of wherein the chronic infection is a mycobacterial infection.11. (canceled)12. The method of wherein the mycobacterial infection is TB.1315-. (canceled)16. The method of wherein the chronic infection is a viral infection caused by a virus selected from the group consisting of HIV claim 1 , HPV claim 1 , HBV and HCV.1720-. (canceled)21. A method of enhancing a Th1 immune response in a subject having a chronic infection comprising administering an antagonist of IL-23.22. The method of wherein the enhanced Th1 immune response comprises a 2-fold or greater increase in the percentage of CD4 T cells expressing IFN-γ compared with the percentage of CD4 T cells expressing IFN-γ prior to administering said antagonist of IL-23.23. The method of wherein the enhanced Th1 immune response comprises a 2-fold or greater decrease in the percentage of CD4 T cells expressing IL-17 compared with the percentage of CD4 T cells expressing IL-17 prior to administering said antagonist of IL-23.24. (canceled)25. The method of further comprising administering at least one of an antagonist of IL-17A claim 1 , IL-6 or TGF-β.2628-. (canceled)29. The method of claim 1 , wherein the antagonist of IL-23 is a binding compound that binds to IL-23p19.30. The method of claim 1 , wherein the antagonist of IL-23 is a binding ...

MAMMALIAN CYTOKINES; RELATED REAGENTS

Purified genes encoding a cytokine or composite cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided. 1. An isolated or recombinant polynucleotide encoding an antigenic polypeptide comprising at least 17 contiguous amino acids from the mature polypeptide from SEQ ID NO: 2 , 4 , 6 , or 8.2. The polynucleotide of claim 1 , encoding a mature polypeptide from SEQ ID NO: 2 claim 1 , 4 claim 1 , 6 claim 1 , or 8.3. The polynucleotide of claim 1 , which hybridizes at 55° C. claim 1 , less than 500 mM salt claim 1 , and 50% formamide to the coding portions of SEQ ID NO: 1 claim 1 , 3 claim 1 , 5 claim 1 , or 7.4. The polynucleotide of claim 3 , comprising at least 35 contiguous nucleotides of the coding portion of SEQ ID NO: 1 claim 3 , 3 claim 3 , 5 claim 3 , or 7.5. An expression vector comprising the polynucleotide of .6. A host cell containing the expression vector of claim 5 , including a eukaryotic cell.7. A method of making an antigenic polypeptide comprising expressing a recombinant polynucleotide of .8. A method for forming a duplex with a polynucleotide of claim 1 , comprising contacting said polynucleotide with a probe that hybridizes claim 1 , under stringent conditions claim 1 , to at least 25 contiguous nucleotides of the coding portion of SEQ ID NO: 1 claim 1 , 3 claim 1 , 5 claim 1 , or 7; thereby forming said duplex.9. A kit for the detection of a polynucleotide of claim 1 , comprising a polynucleotide that hybridizes claim 1 , under stringent hybridization conditions claim 1 , to at least 17 contiguous nucleotides of a polynucleotide of .10. The kit of claim 9 , wherein said probe is detectably labeled.11. A binding compound comprising an antibody binding site which specifically binds to at least 17 contiguous amino acids from SEQ ID NO: 2 claim 9 , 4 claim 9 , 6 claim 9 , or 8.12. The ...

METHODS OF MODULATING CYTOKINE ACTIVITY; RELATED REAGENTS

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, including tumors and cancer. Also provided are methods of administering agonists or antagonists of IL-33 and IL-33 receptor. 1. A method of modulating an immune disorder or condition , comprising administering an effective amount of an agonist or antagonist of IL-33 of IL-33 Receptor complex (IL-33R).2. The method of claim 1 , wherein the disorder or condition comprises:a) innate response;b) asthma or allergy;c) multiple sclerosis;d) an inflammatory bowel disorder;e) arthritis;f) infection;g) a cancer or tumor.3. The method of claim 2 , wherein the infection comprises:a) an intracellular pathogen;b) a bacterium;c) a parasite; ord) a virus.4. The method of claim 3 , wherein the intracellular pathogen is:{'i': 'Leishmania', 'a) sp.;'}{'i': 'Mycobacterium', 'b) sp.;'}{'i': 'Listeria', 'c) sp.;'}{'i': 'Toxoplasma', 'd) sp.;'}{'i': 'Schistosoma', 'e) ; or'}f) a respiratory virus;5. The method of claim 1 , wherein the immune disorder or conditions comprises:a) TH1-type response; orb) TH2-type response.6. The method of claim 5 , wherein the TH2-type response comprises an early event in TH2-type response.7. The method of claim 1 , wherein the arthritis comprises:a) rheumatoid arthritis;b) osteoarthritis; orc) psoriatic arthritis.8. The method of claim 1 , wherein the agonist comprises:a) IL-33 or;b) a nucleic acid.9. The method of claim 8 , wherein the nucleic acid encodes IL-33.10. The method of claim 1 , wherein the antagonist comprises a binding composition from an antibody that specifically binds:a) IL-33;b) an IL-33R complex; orc) a complex of IL-33 and IL-33R.11. The method of claim 10 , wherein the binding composition from an antibody comprises:a) a polyclonal antibody;b) a monoclonal antibody;c) a humanized antibody, or a fragment thereof;{'sub': '2', 'd) an Fab, Fv, or F(ab′)fragment;'}e) a peptide mimetic of an antibody; orf) a detectable ...

COMBINATION OF AN ANTI-IL-10 ANTIBODY AND A CPG-C TYPE OLIGONUCLEOTIDE FOR TREATING CANCER

The present disclosure describes combination therapies comprising an anti-IL-10 antibody or antigen-binding fragment thereof and a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer. 1. A method for treating cancer in a human patient comprising administering to the individual a combination therapy which comprises an anti-IL-10 antibody or antigen-binding fragment thereof and a TLR9 agonist , wherein the TLR9 agonist is a CpG-C type oligonucleotide.2. The method of claim 1 , wherein the anti-IL-10 antibody is a monoclonal antibody claim 1 , a humanized antibody claim 1 , a chimeric antibody claim 1 , or a fully human antibody.3. The method of claim 1 , wherein the anti-IL-10 antibody claim 1 , or antigen binding fragment thereof claim 1 , comprises: (a) light chain CDRs of SEQ ID NOs: 5 claim 1 , 6 and 7 (b) and heavy chain CDRs of SEQ ID NOs: 8 claim 1 , 9 and 10.4. The method of claim 1 , wherein the anti-IL-10 antibody or antigen-binding fragment thereof comprises the heavy chain and light chain variable regions of SEQ ID NO:11 and SEQ ID NO:12.5. The method of claim 1 , wherein the anti-IL-10 antibody or antigen binding fragment thereof is anti-IL-10 hum 12G8 or an antigen binding fragment thereof claim 1 , or an anti-IL-10 hum 12G8 variant or an antigen binding fragment thereof.6. The method of claim 1 , wherein the anti-IL-10 antibody is an anti-IL-10 monoclonal antibody which comprises a heavy chain and a light chain claim 1 , and wherein the heavy chain comprises SEQ ID NO:1 and the light chain comprises SEQ ID NO:2.7. The method of claim 1 , wherein the CpG-C type oligonucleotide consists of:{'sub': x', 'q', 'y', 'w', '1', '2', '2', '1', 'p', 'z,', 'v', '1', '1', '2', '2, '(a) 5′-N(TCG(N))N(XXCGX′X′(CG))N(SEQ ID NO:13) wherein N are nucleosides, x=0, 1, 2 or 3, y=1, 2, 3 or 4, w=0, 1 or 2, p=0 or 1, q=0, 1 or 2, v=0 to 89 and z=1 to 20, Xand X′ are self-complementary nucleosides, and Xand X′ are self- ...

USE OF IL-23 AND IL-17 ANTIAGONISTS TO TREAT AUTOIMMUNE OCULAR INFLAMMATORY DISEASE

Novel methods and drug products for treating autoimmune ocular inflammatory disease are disclosed, which involve administration of agents that antagonize one or both of IL-17 and IL-23 activity. 1. A method of treating a patient for an autoimmune ocular inflammatory disease (AOID) , comprising administering to the patient an IL-23 antagonist.2. The method of claim 1 , wherein the IL-23 antagonist is a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-23p19 or IL-23R.3. The method of claim 1 , wherein a specified dose of the IL-23 antagonist is administered at a specified interval during a first treatment period claim 1 , wherein the specified interval is once per day claim 1 , once per week claim 1 , 2 to 7 times per week claim 1 , once every other week claim 1 , and once per month.4. The method of claim 1 , wherein the duration of the first treatment period is between three months and two years.5. The method of claim 1 , wherein the duration of the first treatment period is between six months and one year.6. The method of claim 1 , wherein the dose of the IL-23 antagonist is gradually reduced during a second treatment period that begins upon the end of the first treatment period.7. The method of claim 1 , wherein the AOID is uveitis.8. A manufactured drug product for treating an autoimmune inflammatory disease (AOID) claim 1 , which comprises(a) a first pharmaceutical formulation comprising an IL-17 antagonist; and(b) a second pharmaceutical formulation comprising an IL-23 antagonist.9. The manufactured drug product of claim 8 , wherein the IL-17 antagonist is a monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17 or IL-17RA and the a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-23p19 or IL-23R.10. The manufactured drug product of claim 8 , wherein the AOID is uveitis. The present application is a divisional of Ser. No. ...

COMBINATION OF A PD-1 ANTAGONIST AND CPG-C TYPE OLIGONUCLEOTIDE FOR TREATING CANCER

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (T1119) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer. 1. A method for treating cancer in an individual comprising administering to the individual a combination therapy which comprises a PD-1 antagonist and a TLR9 agonist , wherein:the PD-1 antagonist is a monoclonal antibody, or antigen binding fragment thereof, which comprises: (a) light chain CDRs of SEQ ID NOs: 1, 2 and 3 and heavy chain CDRs of SEQ ID NOs: 4, 5 and 6; or (b) light chain CDRs of SEQ ID NOs: 7, 8 and 9 and heavy chain CDRs of SEQ ID NOs: 10, 11 and 12 ; and{'sub': 'q', 'the TLR9 agonist is a CpG-C type oligonucleotide, wherein the CpG-C type oligonucleotide comprises 5′-TCG NTTCGA ACG TTC GAA CGT TCG AAT-3′, wherein N are nucleosides and q=4.'}2. (canceled).3. The method of claim 1 , wherein the PD-1 antagonist is a monoclonal antibody claim 1 , or an antigen binding fragment thereof claim 1 , which specifically binds to human PD-1 and blocks the binding of human PD-L1 to human PD-1.4. (canceled).5. The method of claim 3 , wherein the PD-1 antagonist also blocks binding of human PD-L2 to human PD-1.67-. (canceled).8. The method of claim 3 , wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody which comprises a heavy chain and a light chain claim 3 , and wherein the heavy chain comprises SEQ ID NO:21 and the light chain comprises SEQ ID NO: 22.9. The method of claim 3 , wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody claim 3 , which comprises a heavy chain and a light chain claim 3 , and wherein the heavy chain comprises SEQ ID NO:23 and the light chain comprises SEQ ID NO: 24.10. The method of claim 3 , wherein the PD-1 antagonist is pembrolizumab claim 3 , a pembrolizumab variant claim 3 , or nivolumab.1115-. (canceled).16. The method of claim 1 , wherein the ...

COMBINATION OF A PD-1 ANTAGONIST AND CPG-C TYPE OLIGONUCLEOTIDE FOR TREATING CANCER

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer. 1. A method for treating cancer in an individual comprising administering to the individual a combination therapy which comprises a PD-1 antagonist and a TLR9 agonist , wherein the TLR9 agonist is a CpG-C type oligonucleotide.2. The method of claim 1 , wherein the PD-1 antagonist is a monoclonal antibody claim 1 , or an antigen binding fragment thereof.3. The method of claim 1 , wherein the individual is a human and the PD-1 antagonist is a monoclonal antibody claim 1 , or an antigen binding fragment thereof claim 1 , which specifically binds to human PD-L1 and blocks the binding of human PD-L1 to human PD-1.4. The method of claim 1 , wherein the individual is a human claim 1 , and the PD-1 antagonist is a monoclonal antibody claim 1 , or an antigen binding fragment thereof claim 1 , which specifically binds to human PD-1 and blocks the binding of human PD-L1 to human PD-1.5. The method of claim 4 , wherein the PD-1 antagonist also blocks binding of human PD-L2 to human PD-1.6. The method of claim 4 , wherein the PD-1 antagonist is a monoclonal antibody claim 4 , or antigen binding fragment thereof claim 4 , which comprises: (a) light chain CDRs of SEQ ID NOs: 1 claim 4 , 2 and 3 and heavy chain CDRs of SEQ ID NOs: 4 claim 4 , 5 and 6; or (b) light chain CDRs of SEQ ID NOs: 7 claim 4 , 8 and 9 and heavy chain CDRs of SEQ ID NOs: 10 claim 4 , 11 and 12.7. The method of claim 4 , wherein the PD-1 antagonist is a monoclonal antibody claim 4 , or antigen binding fragment thereof claim 4 , which comprises light chain CDRs of SEQ ID NOs: 7 claim 4 , 8 and 9 and heavy chain CDRs of SEQ ID NOs: 10 claim 4 , 11 and 12.8. The method of claim 4 , wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody ...

MAMMALIAN CYTOKINES; RELATED REAGENTS AND METHODS

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided. 150-. (canceled)51. An isolated antibody , or antigen binding fragment thereof , that specifically binds to a complex of an IL-12 p40 polypeptide and an IL-B30 polypeptide , wherein:a) the IL-12 p40 polypeptide comprises the mature sequence of SEQ ID NO:20; andb) the IL-B30 polypeptide comprises the mature sequence of SEQ ID NO:2;wherein the antibody, or antigen binding fragment thereof, binds to sequences within the mature sequence of SEQ ID NO:20 and the mature sequence of SEQ ID NO:2; andfurther wherein the antibody, or antigen binding fragment thereof does not bind to either the mature human IL-12p40 polypeptide alone or the mature human IL-B30 polypeptide alone, andyet further wherein the complex of IL-12p40 and IL-B30 is generated by co-expressing nucleic acids encoding the respective polypeptide chains in a mammalian cell and collecting the IL-12p40/IL-B30 complex secreted from the cell.52. The antibody or antigen binding fragment of comprising a monoclonal antibody or antigen binding fragment thereof.53. The antibody or antigen binding fragment of comprising a humanized antibody or antigen binding fragment thereof.54. The antigen binding fragment of comprising an Fv fragment claim 51 , an Fab fragment claim 51 , or an F(ab′)2 fragment.55. A pharmaceutical formulation comprising:{'claim-ref': {'@idref': 'CLM-00051', 'claim 51'}, 'a) the antibody or antigen binding fragment of ; and'}b) a pharmaceutically acceptable carrier.56. An isolated antibody claim 51 , or antigen binding fragment thereof claim 51 , that specifically binds to a complex of an IL-12 p40 polypeptide and an IL-B30 polypeptide claim 51 , wherein:a) the IL-12 p40 polypeptide consists of the mature sequence of SEQ ID NO:20; andb) the IL-B30 ...

COMPOSITIONS AND METHODS FOR TREATING CANCER WITH A COMBINATION OF PROGRAMMED DEATH RECEPTOR (PD-1) ANTIBODIES AND A CXCR2 ANTAGONIST

The present invention relates to methods of treating a cell proliferation disorder (e.g., cancer) comprising administering: (a) a compound having the Formula (I), wherein Ror Rare as herein defined, or a pharmaceutically acceptable salt thereof; and (b) an anti-human PD-1 antibody or antigen binding fragment thereof to a human patient in need thereof. Also disclosed are therapeutic combinations and kits containing such agents for the treatment of cancers. 2. The method of claim 1 , wherein the cell-proliferation disorder is cancer.3. The method of claim 2 , wherein the cancer is prostate cancer claim 2 , pancreatic cancer claim 2 , melanoma claim 2 , non-small cell lung cancer claim 2 , head and neck cancer claim 2 , urothelial cancer claim 2 , breast cancer claim 2 , gastrointestinal cancer claim 2 , multiple myeloma claim 2 , hepatocellular cancer claim 2 , non-Hodgkin lymphoma claim 2 , renal cancer claim 2 , Hodgkin lymphoma claim 2 , mesothelioma claim 2 , metastatic claim 2 , microsatellite instability-high cancer claim 2 , mismatch repair deficient cancer claim 2 , ovarian cancer claim 2 , small cell lung cancer claim 2 , esophageal cancer claim 2 , anal cancer claim 2 , biliary tract cancer claim 2 , colorectal cancer claim 2 , cervical cancer claim 2 , thyroid cancer claim 2 , or salivary cancer.4. The method of claim 2 , wherein the cancer is prostate cancer.5. The method of claim 4 , wherein the prostate cancer is metastatic castrate-resistant prostate cancer.6. The method of claim 2 , wherein the cancer is pancreatic cancer.7. The method of claim 6 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma.11. The method of claim 1 , wherein the human patient is administered:(a) 200 mg or 240 mg of the anti-human PD-1 antibody or antigen binding fragment thereof and from 5 to 200 mg of the compound of Formula I or a pharmaceutically acceptable salt thereof; or(b) 2 mg/kg of an anti-human PD-1 antibody or antigen binding fragment thereof and from ...

PD1 AND/OR LAG3 BINDERS

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

PD1 AND/OR LAG3 BINDERS

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

PD1 AND/OR LAG3 BINDERS

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided. 121-. (canceled)22: A method for preventing lymphocyte activation gene 3 (LAG3) from binding to MHC class II comprising contacting said LAG3 with a LAG3 binder comprising an immunoglobulin single variable domain (ISVD) that binds to LAG3 comprising a CDR1 comprising the amino acid sequence GRTFSDYVMG (SEQ ID NO: 65) or DYVMG (amino acids 6-10 of SEQ ID NO: 65); a CDR2 comprising the amino acid sequence AISESGGRTHYADXVKG (SEQ ID NO: 66) or AISESGGRTH (amino acids 1-10 of SEQ ID NO: 66); and a CDR3 comprising the amino acid sequence TLLWWTSEYAPIKANDYDY (SEQ ID NO: 67); and , optionally , a half-life extender and/or a C-terminal extender.2327-. (canceled)29: The method of claim 22 , wherein the LAG3 binder is in association with a further therapeutic agent.30: The method of claim 22 , wherein the LAG3 binder further includes a C-terminal extender claim 22 , which is an alanine residue.31: The method of claim 22 , wherein the LAG3 binder further includes a half-life extender comprising an ISVD that binds human serum albumin wherein the ISVD comprises a CDR1 comprising the amino acid sequence GFTFSSFGMS (SEQ ID NO: 60) or SFGMS (SEQ ID NO:151); a CDR2 comprising the amino acid sequence SISGSGSDTLYADSVKG (SEQ ID NO: 61) or SISGSGSDTL (SEQ ID NO:152); and a CDR3 comprising the amino acid sequence GGSLSR (SEQ ID NO: 62).34: The method of claim 33 , wherein the PD1 binder further includes a polypeptide linker that links the C-terminus of the ISVD that binds PD1 to the N-terminus of the ISVD that binds human serum albumin claim 33 , wherein the polypeptide ...

BINDERS PD1 AND / OR LAG3

CTLA4 LIGAND, LINKER, CONTAINER OR INJECTION DEVICE, POLYNUCLEOTIDE, VECTOR, HOST CELL, METHODS FOR MAKING CTLA4 LIGAND AND TO PREVENT CTLA4 FROM CONNECTING TO CD80 OR CD86 AND USES OF SUCH CTLA4 LIGAND

ligantes de ctla4. a presente invenção fornece moléculas, como isvds e nanocorpos, que se ligam à ctla4 ou albumina sérica humana. essas moléculas foram modificadas a fim de reduzir a incidência de ligação por anticorpos pré-existentes nos corpos de um indivíduo administrado com tal molécula. são fornecidos métodos para aumentar a resposta imunológica, tratar câncer e/ou tratar uma doença infecciosa com tais moléculas. ctla4 ligands. the present invention provides molecules, such as isvds and nanobodies, that bind to ctla4 or human serum albumin. these molecules have been modified in order to reduce the incidence of binding by pre-existing antibodies in the bodies of an individual administered such a molecule. methods are provided for enhancing the immune response, treating cancer and/or treating an infectious disease with such molecules.

Mammalian cytokines; related reagents and methods

Nucleic acids encoding mammalian, e.g., rodent, IL-1δ, IL-1ε, purified IL-1δ and IL-1ε proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are provided.

Mammalian cytokines; related reagents and methods

Interleukin-17 related mammalian cytokines. Polynucleotides encoding them. Uses

CTLA-8 related antigens from mammals, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding said antigens. Methods of using said reagents and diagnostic kits are also provided

Mammalian interleukin-12 P40 and interleukin B30, combinations thereof, antibodies, uses in pharmaceutical compositions

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Mammalian receptor protein DCRS5;methods of treatment

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

CYTOKIN RECEPTOR SUBUNITS PROTEINS FROM MAMMALS, ASSOCIATED REAGENTS AND METHODS

Combination therapy comprising an il-23 antagonist and a cytokine antagonist for treatment of immune disorders

Disclosed is a bispecific antibody, or antigen binding fragment thereof, that specifically binds to IL-23R and CD161.

Combination of a pd-1 antagonist and cpg-c type oligonucleotide for treating cancer.

La presente descripción describe terapias de combinación que comprenden un antagonista del Receptor de Muerte Programada 1 (PD-1) y un agonista del Receptor Tipo TolI 9 (TLR9) que es un oligonucleótido tipo CpG-C, y el uso de las terapias de combinación para el tratamiento de cáncer.

Mammalian cytokine related to il10

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Use for interleukin-33 (IL33) and the IL-33 receptor complex

PD1 and / or Lag3 Binding Molecules (Divisional Application 1327-2018)

La presente invención proporciona moléculas, tales como ISVDs y nanocuerpos, que se unen a PD1 y LAG3 y opcionalmente a albúmina sérica humana. Estas moléculas han sido modificadas por ingeniería genética con el fin de reducir la incidencia de la unión por anticuerpos pre-existentes en el cuerpo de un sujeto a quien se administra esta molécula. Se proporcionan métodos para aumentar la respuesta inmune, tratar un cáncer y/o tratar una enfermedad infecciosa con estas moléculas. The present invention provides molecules, such as ISVDs and nanobodies, that bind PD1 and LAG3 and optionally human serum albumin. These molecules have been genetically engineered in order to reduce the incidence of binding by pre-existing antibodies in the body of a subject to whom this molecule is administered. Methods are provided for increasing the immune response, treating cancer, and / or treating infectious disease with these molecules.

PD1 and/or LAG3 binders

PD1 AND/OR LAG3 BINDERS ABSTRACT The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Method of treating asthma or allergy by administering an IL-33 receptor antibody

Provided herein are methods of modulating IL-33 activity, e.g., for the purpose of treating immune diseases and conditions, as well as methods of screening for compounds capable antagonizing IL-33 signaling.

Anti-pd-1/lag3/tigit trispecific antibodies and anti-pd-1/lag3 bispecific antibodies

Provided herein are treatments of conditions ameliorated by counteracting tumor mediated immune suppression. More specifically, provided herein are anti-PD-1/LAG-3/TIGIT trispecific antibodies, anti-PD-1/LAG3 bispecific antibodies, anti-LAG3 antibodies and antigen-binding fragments. Also provided here are methods and uses of these antibodies and antigen-binding fragments in the treatment of cancer or infectious disease.

Human interleukin-1j and antagonists thereof

Mammalian Receptor Proteins; Related Reagents and Methods

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Ctla4 binders.

La presente invención proporciona moléculas, tales como ISVD y nanocuerpos, que se unen a CTLA4 o seroalbúmina humana. Estas moléculas se han diseñado con el fin de reducir la incidencia de la unión por anticuerpos preexistentes en el cuerpo de un sujeto administrado con una molécula de este tipo. Se proporcionan métodos para incrementar la respuesta inmunitaria, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.

Pd1 and/or lag3 binders.

La presente invención proporciona moléculas, tales como ISVD y nanocuerpos, que unen PD1 y LAG3, y opcionalmente a seroalbúmina humana. Estas moléculas se han diseñado con el fin de reducir la incidencia de la unión por anticuerpos preexistentes en el cuerpo de un sujeto administrado con una molécula de este tipo. Se proporcionan procedimientos para incrementar la respuesta inmunitaria, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.

TOLL TYPE RECEIVING HUMAN PROTEINS, ASSOCIATED REAGENTS AND METHODS.

Una proteína o péptido esencialmente puros o recombinantes con actividad de receptor de tipo Toll, donde dicha proteína o péptido muestra una identidad de secuencia de al menos 70% con el SEQ ID NO: 6 a lo largo de toda su longitud.

Mammalian cytokines; related reagents and methods

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Combination therapy for treatment of immune disorders

Methods and compositions are provided for the treatment of immune disorders, such as autoimmune diseases, or cancers, involving combination therapy with agents that inhibit the development or maintenance of Th17 cells. Treatment regimens are provided in which an antagonist of a pro-inflammatory cytokine is administered for a time sufficient to alleviate signs and symptoms of an acute phase flare-up of the autoimmune disease, or cancer, and treatment with an antagonist of IL-23 is continued for a longer time to prevent recurrence of the acute event. Antagonists of PGE2 and CD 161 are also disclosed for use in treatment of autoimmune, inflammatory and proliferative disorders.

Mammalian cytokines; receptors; related reagents and methods

Nucleic acids encoding mammalian cytokine receptor, e.g., for cytokine IL-B50, purified proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Compositions and methods for treating cancer with a combination of programmed death receptor (PD-1) antibodies and a CXCR2 antagonist

The present invention relates to methods of treating a cell proliferation disorder (e.g., cancer) comprising administering: (a) a compound having the Formula (I), wherein R1 or R2 are as herein defined, or a pharmaceutically acceptable salt thereof; and (b) an anti-human PD-1 antibody or antigen binding fragment thereof to a human patient in need thereof. Also disclosed are therapeutic combinations and kits containing such agents for the treatment of cancers.

Methods of generating antibodies against cytokines

Methods of generating antibodies directed to human or murine cytokines are provided.

Mammalian cytokines; related reagents and methods

Nucleic acids encoding mammalian, e.g., rodent IL-1δ, IL-1ε, purified IL-1δ and IL-1ε proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are provided.

Mammalian receptor proteins; related reagents and methods

Human receptor proteins; related reagents and methods

Mammalian Receptor Proteins; Related Reagents and Methods

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Combination of a pd-1 antagonist and cpg-c type oligonucleotide for treating cancer

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.

Human Receptor Proteins; Related Reagents and Methods

Nucleic acids encoding mammalian Toll-like receptors (TLRs) have been identified in human cells. Recombinantly produced TLRs are used in the preparation of antibodies that are capable of binding to the TLRs. The antibodies are advantageously used in the prevention and treatment of septic shock, inflammatory conditions, and viral infections.

Mammalian interleukin-12 p40 and interleukin b30. combinations thereof. antibodies. uses in pharmaceutical compositions

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Mammalian cytokines; related reagents and methods

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Ctla4 binders

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Methods of modulating cytokine activity; related reagents

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, including tumors and cancer. Also provided are methods of administering agonists or antagonists of IL-33 and IL-33 receptor.

Ctla4 binders

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Purification of human interleukin-4 expressed in escherichia coli

A method is provided for refolding and purifying biologically active human interleukin-4 from insoluble aggregates in bacteria. The method comprises solubilizing the aggregates with an aqueous solution containing a chaotropic agent and a reducing agent, followed by steps of controlled and sequential reduction in the concentrations of the two agents to form biologically active human interleukin-4. Finally the biologically active human interleukin-4 is separated from inactive material by standard biochemical procedures.

COMBINATION OF ANTI-IL-10 ANTIBODY AND CPG-C OLIGONUCLEOTIDE FOR THE TREATMENT OF CANCER

Mammalian cytokines; related reagents

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic ki ts are also provided.

Method of treating skin inflammation

Provided are methods for diagnosing the propensity of a subject to develop skin inflammation, in particular, psoriasis. Also provided are methods of treatment with antagonists of IL-17 and/or IL-23.

Methods of generating antibodies against cytokines

Human receptor proteins; related reagents and methods

Nucleic acids encoding mammalian Toll-like receptors (TLRs) have been identified in human cells. Recombinantly produced TLRs are used in the preparation of antibodies that are capable of binding to the TLRs. The antibodies are advantageously used in the prevention and treatment of septic shock, inflammatory conditions, and viral infections.

Mammalian genes; related reagents and methods

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Uses of il-23 antagonists in the treatment of diabetes mellitus

Provided are methods of treatment for inflammatory and autoimmune disorders of the metabolic system. Also provided are methods of diagnosis.

INTERLEUKIN-17 Mammalian Cytokines. POLYNucleotides coding for them. uses

Αντιγόνα από θηλαστικά που σχετίζονται με CTLA-8, αντιδραστήρια που σχετίζονται με αυτά περιλαμβανομένων πρωτεϊνών, ειδικών αντισωμάτων και νουκλεϊκών οξέων που κωδικοποιούν τα εν λόγω αντιγόνα. Παρέχονται επίσης μέθοδοι για χρησιμοποίηση των εν λόγω αντιδραστηρίων και διαγνωστικών κιτ. Antigens from mammals associated with CTLA-8, related reagents including proteins, specific antibodies, and nucleic acids encoding said antigens. Methods for using said reagents and diagnostic kits are also provided.

Mammalian receptor proteins; related reagents and methods

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Use of an il-23 antagonist for the treatment of a fungal infection.

Uso de un antagonista de la il-23 para elaborar un medicamento para el tratamiento de una infección. Use of an il-23 antagonist to develop a medication for the treatment of an infection.

CTLA4 LINKS

La presente invención proporciona moléculas, tales como ISVD y nanocuerpos, que se unen a CTLA4 o albúmina sérica humana. Estas moléculas se han diseñado con el fin de reducir la incidencia de la unión por anticuerpos preexistentes en el cuerpo de un sujeto administrado con una molécula de 5 este tipo. Se proporcionan procedimientos para incrementar la respuesta inmunitaria, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.

Combination of a pd-1 antagonist and cpg-c type oligonucleotide for treating cancer

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.

Mammalian Cytokines; Related Reagents and Methods

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Mammalian cytokines; receptors; related reagents and methods

Mammalian cytokines; related reagents and methods

Mammalian cytokine related to il10

Linkers of pd1 and / or lag3

La presente invención proporciona moléculas, tales como ISVD y nanocuerpos, que se unen a PD1 y LAG3 y opcionalmente a albúmina sérica humana. Estas moléculas se han diseñado con el fin de reducir la incidencia de la unión por anticuerpos preexistentes en el cuerpo de un sujeto administrado con una molécula de este tipo. Se proporcionan procedimientos para incrementar la respuesta inmunitaria, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.

Combination of an anti-il-10 antibody and a cpg-c type oligonucleotide for treating cancer

The present disclosure describes combination therapies comprising an anti-IL-10 antibody or antigen-binding fragment thereof and a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.

Ctla4 binding proteins.

La presente invención proporciona moléculas, corno ISVDs y Nanocuerpos, que se unen a CTLA4 o albúmina sérica humana. Estas moléculas han sido modificadas para reducir la incidencia de unión por anticuerpos preexistentes en los cuerpos de un sujeto al que se le administró dicha molécula. Se proporcionan métodos para aumentar la respuesta inmune, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.  The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. These molecules have been modified to reduce the incidence of binding by preexisting antibodies in the bodies of a subject to which said molecule was administered. Methods for increasing the immune response, treating cancer and / or treating an infectious disease with said molecules are provided.

Mammalian Cytokines, Resistant Reagents

Παρέχονται εξαγνισμένα γονίδια που κωδικοποιούν κυτοκίνη από ένα θηλαστικό, αντιδραστήρια που σχετίζονται με αυτή περιλαμβανομένων των εξαγνισμένων πρωτεϊνών, ειδικών αντισωμάτων, και νουκλεϊκών οξέων που κωδικοποιούν αυτό το μόριο. Παρέχονται επίσης μέθοδοι χρήσης των εν λόγω αντιδραστηρίων και διαγνωστικά κιτ. Purified cytokine-encoding genes from a mammal, related reagents including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using these reagents and diagnostic kits are also provided.

Agonists and antagonists of p28 ebi3 and wsx/tccr for treating immune disorders

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders. Also provided are methods of administering agonists or antagonists of IL-27 and IL-27 receptor.

IL-23 and its receptor; related reagents and methods

Combination therapy for treatment of immune disorders

Methods and compositions are provided for the treatment of immune disorders, such as autoimmune diseases, or cancers, involving combination therapy with agents that inhibit the development or maintenance of Th17 cells. Treatment regimens are provided in which an antagonist of a pro-inflammatory cytokine is administered for a time sufficient to alleviate signs and symptoms of an acute phase flare-up of the autoimmune disease, or cancer, and treatment with an antagonist of IL-23 is continued for a longer time to prevent recurrence of the acute event. Antagonists of PGE2 and CD 161 are also disclosed for use in treatment of autoimmune, inflammatory and proliferative disorders.

IL-12P40 and IL-B30 polypeptide complex

Purified genes encoding cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this molecule are provided. Methods of using said reagents and diagnostic kits are also provided.

Use of IL-23 and IL-17 Antagonists in the Treatment of Autoimmune Eye Inflammatory Disease

Combination therapy for treatment of immune disorders

Methods and compositions are provided for the treatment of immune disorders, such as autoimmune diseases, or cancers, involving combination therapy with agents that inhibit the development or maintenance of Th17cells. Treatment regimens are provided in which an antagonist of a pro-inflammatory cytokine is administered for a time sufficient to alleviate signs and symptoms of an acute phase flare-up of the autoimmune disease, or cancer, and treatment with an antagonist of IL-23 is continued for a longer time to prevent recurrence of the acute event. Antagonists of PGE2 and CD 161 are also disclosed for use in treatment of autoimmune, inflammatory and proliferative disorders.

Mammalian receptor protein DCRS5; methods of treatment

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Ανθρωπινος πρωτεϊνικος υποδοχεας τυπου toll, σχετικα αντιδραστηρια και μεθοδοι

Νουκλεϊκά οξέα που κωδικοποιούν εννέα ανθρώπινους υποδοχείς, ονομαζόμενοι DNAX υποδοχείς 2-10 τύπου Toll (DTLR2-10), ομόλογοι του υποδοχέα Toll της δροσόφιλας και του ανθρώπινου υποδοχέα IL-1, εξαγνισμένες πρωτεΐνες DTLR και θραύσματα τους, μονόκλωνα/πολύκλωνα αντισώματα εναντίον αυτών των υποδοχέων, και μέθοδοι για διαγνωστική και θεραπευτική χρήση.

Pd1 and/or lag3 binders

Abstract The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided. Date Recue/Date Received 2021-09-27

Combination of a PD-1 antagonist and CpG-C type oligonucleotide for treating cancer

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.

Proteinas de union a pd1 y/o lag3.

La presente invención proporciona moléculas, tales como ISVD y nanocuerpos, que unen PD1 y LAG3, y opcionalmente a seroalbúmina humana. Estas moléculas se han diseñado con el fin de reducir la incidencia de la unión por anticuerpos preexistentes en el cuerpo de un sujeto administrado con una molécula de este tipo. Se proporcionan procedimientos para incrementar la respuesta inmunitaria, tratar cáncer y/o tratar una enfermedad infecciosa con dichas moléculas.

Menschliche toll-ähnliche rezeptorproteine, zugehörige reagenzien und verfahren

Anti-pd-1/lag3/tigit trispecific antibodies and anti-pd-1/lag3 bispecific antibodies

Menschliche toll-like-rezeptorproteine, zugehörige reagenzien und verfahren

Pd1 and/or lag3 binders

Abstract The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided. Date Recue/Date Received 2021-09-27

Menschliche toll-ähliche rezeptorproteine, zugehörige reagenzien und verfahren