АНТИТЕЛА ПРОТИВ IL2

... 1. Гуманизированное моноклональное антитело или его фрагмент, которые специфически связываются с человеческим интерлейкином-2 (IL2), ! где указанное гуманизированное моноклональное антитело нейтрализует активность человеческого IL2 путем связывания с указанным человеческим IL2 до, во время и/или после связывания указанного человеческого IL2 с человеческим рецептором IL2, и ! где вариабельная область легкой цепи указанного гуманизированного моноклонального антитела содержит в ее второй каркасной области последовательность смежных аминокислот КАРКА. ! 2. Гуманизированное моноклональное антитело или его фрагмент по п.1, где последовательность смежных аминокислот КАРКА находится в аминокислотных положениях 42-46 второй каркасной области. ! 3. Гуманизированное моноклональное антитело или его фрагмент по п.1, где, по меньшей мере, одна из первой, третьей и/или четвертой каркасной области легкой цепи соответствует(ют) последовательности этой области/этих областей в человеческой зародышевой линии ...

Method for obtaining vaccines for preventing the pathgenic effects related to a retroviral infection.

The invention concerns a method for obtaining a vaccine against the pathogenic effects related to infection of a host by a retrovirus, in the event that the target cells of the retrovirus have a membrane receptor for a protein of the host and the viral infection induces an an immune response directed both against an envelope protein of the virus and against an envelope protein of the virus and against a protein of the host. The method consists in preparing a vaccine agent based on polypeptide comprising a fragment of an immunodominant and preserved zone of the retrovirus envelope protein, in a modified form such that the vaccine agent induces an immune response directed against the envelope protein and not against the host protein.

Obtaining vaccines intended to prevent the pathogenic effects associated with an infection retrovirale.

Method for obtaining vaccines for preventing the pathogenic effects related to a retroviral infection

THE USE OF PEPTIDEN OF IL-2 AND PEPTID DERIVATIVES AS THERAPEUTIC ACTIVE SUBSTANCES

Interleukin-2 muteins for the expansion of T-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgGI Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Dual OX40 agonist/IL-2 cancer therapy methods

OX40 is a potent immune stimulating target. Provided herein is a method of treating cancer, which includes administering to a subject in need of treatment an OX40 agonist and a common gamma chain (yc) cytokine or an active fragment, variant, analog, or derivative thereof In certain aspects the common gamma chain (yc) cytokine is interleukin-2 (IL-2) or an active fragment, variant, analog, or derivative thereof. Combined treatment with an agonist anti-OX40 mAb and IL-2 synergized to augment tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8 ...

Methods and compositions for promoting hair growth

The presently disclosed subject matter relates, in certain embodiments, to compositions and methods for the inhibition of the JAK-STAT pathway in order to induce hair growth. In certain embodiments, the presently disclosed subject matter relates to topical treatments with small molecule inhibitors of the JAK-STAT pathway to induce hair growth.

Interleukin-2 muteins for the expansion of T-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Method for obtaining vaccines for preventing the pathogenic effects related to aretroviral infection

IMMUNOMODULATING POLYMERS

Methods and products for inducing IL-2 secretion, inducing IL-10 secretion, activating T cells, suppressing IgG antibody response to specific antigen, promoting allograft survival, reducing postoperative surgical adhesion formation, and protecting against abscess formation associated with surgery, trauma or diseases that predispose the host to abscess formation are provided. The methods of the invention are accomplished using an immunomodulator which is a polymer having at least two repeating charge motifs separated by at least a certain minimum distance.

ENGINEERED HETERODIMERIC PROTEIN DOMAINS

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

Treatment of familial Mediterranean Fever with anti IL-1beta antibodies

Targeted Immunotolerance

Methods and compounds for conferring site-specific or local immune privilege. 1. A polypeptide comprising a targeting moiety that binds to a target cell and an effector binding/modulating moiety , wherein the effector binding/modulating moiety is a IL-2 mutein polypeptide (IL-2 mutein).2. The polypeptide of claim 1 , wherein the targeting moiety comprises an antibody that binds to a target protein on the surface of a target cell.3. The polypeptide of claim 1 , wherein the antibody is an antibody that binds to MAdCAM claim 1 , OAT1 claim 1 , OCT2 claim 1 , FXYD2 claim 1 , TSPAN7 claim 1 , DPP6 claim 1 , HEPACAM2 claim 1 , TMEM27 claim 1 , or GPR119.46-. (canceled)7. The polypeptide of claim 1 , wherein the targeting moiety comprises an anti-MAdCAM antibody.819-. (canceled)20. The polypeptide of claim 1 , wherein the IL-2 mutein comprises a IL-2 sequence of SEQ ID NO: 6 claim 1 , wherein peptide comprises a mutation at a position that corresponds to position 53 claim 1 , 56 claim 1 , 80 claim 1 , or 118 of SEQ ID NO: 6.21. (canceled)22. The polypeptide of claim 20 , wherein the mutation is a L to I mutation at position 53 claim 20 , 56 claim 20 , 80 claim 20 , or 118.23. (canceled)24. The polypeptide of claim 20 , further comprising a mutation at one or more positions of 29 claim 20 , 31 claim 20 , 35 claim 20 , 37 claim 20 , 48 claim 20 , 69 claim 20 , 71 claim 20 , 74 claim 20 , 88 claim 20 , and 125 in SEQ ID NO: 6.25. (canceled)26. The polypeptide of claim 1 , wherein the mutation in the mutein is one or more of E15Q claim 1 , H16N claim 1 , Q22E claim 1 , D84N claim 1 , E95Q claim 1 , or Q126E.27. The polypeptide of any of the preceding claims claim 1 , wherein the mutein comprises a N29S claim 1 , Y31S claim 1 , Y51H claim 1 , K35R claim 1 , T37A claim 1 , K48E claim 1 , V69A claim 1 , N71R claim 1 , Q74P claim 1 , N88D claim 1 , N88R claim 1 , C125A claim 1 , or C125S mutation in SEQ ID NO: 6.2836-. (canceled)37. The polypeptide of claim 1 , wherein the IL-2 ...

IMMUNOCYTOKINE COMBINATION THERAPY

This invention relates to methods and compositions, in a combination therapy, for treatment of neoplastic disease, including tumors and cancer, wherein an immunocytokine and a small molecule drug conjugate which comprises a moiety capable of binding to a tumor-associated target, e.g., capable of binding to carbonic anhydrase IX (CAIX), are administered. In preferred embodiments, the immunocytokine comprises an antibody targeting the ED-B or ED-A domain of fibronectin and interleukin-2, and the small molecule drug conjugate comprises a ligand moiety capable of binding to CAIX, a linker, and a cytotoxic drug. 3. (canceled)4. The composition of claim 2 , wherein the SMDC comprises:(c) a ligand moiety capable of binding to CAIX,(d) a linker, and(e) a cytotoxic drug.5. (canceled)6. The composition of claim 4 , wherein the moiety capable of binding to CAIX has a terminal sulfonamide (—SONH) claim 4 , sulfamate (—OSONH) or sulfamide (—NHSONH) group.7. (canceled)9. (canceled)10. The composition of claim 1 , wherein the drug is a cytotoxic drug.11. The composition of claim 10 , wherein the cytotoxic drug is selected from the group consisting of dolastatin claim 10 , a dolastatin analogue claim 10 , and a dolastatin derivative.12. (canceled)13. The composition of claim 4 , wherein the drug is attached to the ligand by a cleavable linker.14. (canceled)15. The composition of claim 13 , wherein the linker is selected from valine-citrulline or valine-alanine.16. (canceled)17. The composition of claim 1 , wherein the cytokine is an interleukin selected from the group consisting of IL-2 claim 1 , IL-12 and TNF.18. The composition of claim 1 , wherein the antibody fragment is selected from the group consisting of ScFv claim 1 , diabody and SIP.19. The composition of claim 13 , wherein the cleavable linker comprises(1) a disulfide bond;(2) an amide linkage; or(3) an ester linkage.20. The composition of claim 19 , wherein claim 19 , when the cleavable linker comprises(1) a disulfide ...

ENGINEERED ANTI-IL-2 ANTIBODIES

Inhibition of IL-2 production

Anti-IL2 antibodies

IMMOBILIZATION OF GLYCOPROTEINS

Interleukin-2 receptor associated polypeptides

Interleukin-2 muteins for the expansion of T-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgGI Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Methods for improving graft acceptance in a recipient by administration of a cytokine profile altering agent

Engineered heterodimeric protein domains

IL2Rbeta/common gamma chain antibodies

Anti-CD122 and/or γc antibodies and fragments thereof are disclosed. Also disclosed are compositions comprising such antibodies and fragments, and uses and methods using the same.

Methods and arrays for use in biomarker detection for prostate cancer

The invention provides a method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of: (a) providing a sample to be tested from the individual; and (b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1; wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual. The invention also provides arrays and kits for use in the same.

Methods and arrays for use in biomarker detection for prostate cancer

The invention provides a method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of: (a) providing a sample to be tested from the individual; and (b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1; wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual. The invention also provides arrays and kits for use in the same.

METHODS FOR IMPROVING GRAFT ACCEPTANCE IN A RECIPIENT BY ADMINISTRATION OF A CYTOKINE PROFILE ALTERING AGENT

Methods for improving graft acceptance in a recipient by administration of a cytokine profile altering agent are disclosed. The methods involve biasing the cytokine response in a graft recipient to one dominated by Th2 cytokines either by increasing Th2 cytokine production or by decreasing Th1 cytokine production by administering an isolated cell and a cytokine profile altering agent to the subject to thereby promote acceptance of the graft in the subject.

IL2RBETA/COMMON GAMMA CHAIN ANTIBODIES

Anti-CD122 and/or ?c antibodies and fragments thereof are disclosed. Also disclosed are compositions comprising such antibodies and fragments, and uses and methods using the same.

METHODS AND COMPOSITIONS FOR PROMOTING HAIR GROWTH

The presently disclosed subject matter relates, in certain embodiments, to compositions and methods for the inhibition of the JAK-STAT pathway in order to induce hair growth. In certain embodiments, the presently disclosed subject matter relates to topical treatments with small molecule inhibitors of the JAK-STAT pathway to induce hair growth.

ENGINEERED HETERODIMERIC PROTEIN DOMAINS

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein- protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

CANCER-TARGETED IL-12 IMMUNOTHERAPY

The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and / or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and / or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases.

IMMUNOMODULATORY METHODS AND SYSTEMS FOR TREATMENT AND/OR PREVENTION OF HYPERTENSION

Immunomodulatory agents, T cell, compositions, methods and systems for treating and/or preventing hypertension and/or a condition associated thereto in an individual.

IMMUNOSTIMULATING HUMANIZED MONOCLONAL ANTIBODIES AGAINST INTERLEUKIN - 2 FUSION PROTEINS AND THEIR HUMAN

METHOD OF TREATMENT OF PATHOLOGICAL SYNDROME AND MEDICINAL AGENT

THWART IMMUNOLOGICAL TOLERANCE

For generating and delivery from stem cells useful factor method and apparatus

항-IL-2 항체 및 조성물 및 이의 용도

... 본 발명은 IL-2에 특이적으로 결합하여, IL-2Rα 및 IL-2Rβ에 대한 IL-2 결합의 친화도를 감소시키는, 항체, 또는 이의 항원-결합 부분을 제공한다. 본 발명은 상기 항체 및 이를 암호화하는 핵산을 수득하는 방법을 추가로 제공한다. 본 발명은 상기 항체 및 IL-2를 포함하는 복합체를 투여하는 단계를 포함하지만, 이것으로 제한되지 않는, 자가면역 질환, 장애 또는 병태를 치료 및/또는 예방하고, 면역억제를 위한 이러한 항체의 조성물 및 이러한 항체를 사용하는 치료 방법을 추가로 제공한다.

"obtenção de vacinas destinadas a prevenir os efeitos patogênicos associados a uma infecção retroviral"

ENGINEERED HETERODIMERIC PROTEIN DOMAINS

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included. 116-. (canceled)17. A method of colocalizing bio-active domains when administered to a biological system , the method comprising the step of administering to the biological system a multimeric protein comprising at least first and second nonidentical engineered domains , each of the first and second engineered domains containing a protein-protein interaction interface comprising amino acid sequence segments derived from two or more naturally occurring homologous parent domains , thereby conferring on said first and second engineered domains assembly specificities distinct from assembly specificities of the parent domains , wherein the first and second engineered domains form heterodimers with one another preferentially over forming homodimers , wherein the multidomain protein comprises a first bio-active domain comprising an antibody variable domain , and wherein the multidomain protein further comprises a second bio-active domain comprising a second antibody variable domain with distinct specificity.18. The method of claim 17 , wherein the biological system is a mammal.1935-. (canceled) This application is a divisional of U.S. application Ser. No. 15/362,319, filed Nov. 28, 2016, which is a divisional of U.S. application Ser. No. 14/505,653, filed on Oct. 3, 2014 (U.S. Pat. No. 9,505,848, issued Nov. 29, 2016), which is a divisional of U.S. application Ser. No. 11/728,048, ...

Method of treating a pathological syndrome and a pharmaceutical agent

A method of treating a pathological syndrome includes administration of an activated form of ultra-low doses of antibodies to an antigen, wherein said activated form is obtained by repeated consecutive dilution combined with external impact, and the antigen is a substance or a pharmaceutical agent exerting influence upon the mechanisms of formation of this particular pathological syndrome. Pharmaceutical agent for treating a pathological syndrome contains activated form of ultra-low doses of monoclonal, polyclonal or natural antibodies to an antigen, wherein said activated form is prepared by means of repeated consecutive dilution and external treatment, predominantly based on homeopathic technology, and said antigen is a substance or a drug acting as a direct cause of the pathological syndrome or involved in regulation of mechanisms of its formation. At that, activated forms of ultra-low doses of antibodies are raised against antigens of exogenous or endogenous origin, against autologous ...

АКТИВИРУЕМЫЕ ПОЛИПЕПТИДЫ ИНТЕРЛЕЙКИНА-2 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Изобретение относится к области биотехнологии, конкретно к получению слитых белков, которые являются кондиционально активными вариантами интерлейкина 2 (IL-2), и может быть использовано в медицине для лечения опухоли. Предложен кондиционально активный IL-2, содержащий слитый полипептид, в состав которого входит полипептид IL-2, элемент для продления времени полужизни и блокирующий IL-2 фрагмент, соединенные линкерами. Изобретение обеспечивает получение кондиционально активного пролекарства IL-2 с увеличенным периодом полужизни, которое доставляет активный IL-2 после расщепления протеазой, в частности, в желаемые места активности, такие как микроокружение опухоли. 4 н. и 6 з.п. ф-лы, 23 ил., 3 табл., 13 пр.

НОВОЕ ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ИЛ-1β

FIELD: medicine. SUBSTANCE: presented group of inventions refers to medicine. What is presented is application of IL-1β binding antigen for producing a drug preparation for treating juvenile rheumatoid arthritis in a patient, containing at least one antigen-binding centre which involves a first domain having an amino acid sequence specified in SEQ ID NO:1, and a second domain having an amino acid sequence specified in SEQ ID NO:2. What is presented is a pharmaceutical composition containing said antibody in a combination with pharmaceutically acceptable excipients, solvents or carriers introduced parenterally. EFFECT: presented group of inventions provides new application of IL-1β binding antibody for treating juvenile rheumatoid arthritis, particularly systemic idiopathtic juvenile rheumatoid arthritis in mammals, particularly in a human. 10 cl, 3 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 468 817 (13) C2 (51) МПК A61K 39/395 (2006.01) A61P 19/02 (2006.01) A61P 37/02 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2008120625/15, 24.10.2006 (24) Дата начала отсчета срока действия патента: 24.10.2006 (73) Патентообладатель(и): НОВАРТИС АГ (CH) R U Приоритет(ы): (30) Конвенционный приоритет: 26.10.2005 US 60/730,435 02.12.2005 US 60/742,125 (72) Автор(ы): ЛОУ Фил (CH), ГРАМ Германн (DE), ЮНГ Томас (AT), РАЙТ Тимоти (US), МУНДЕЛ Тревор (US) (43) Дата публикации заявки: 20.01.2010 Бюл. № 2 2 4 6 8 8 1 7 2 4 6 8 8 1 7 R U (56) Список документов, цитированных в отчете о поиске: WO 02/16436 А2, 28.02.2002. WO 95/01997, 19.01.1997. WO 2004/067568 А2, 12.08.2004. WO 03/010282 А2, 06.02.2003. WO 01/53353 А2, 26.07.2001. HAWKINS P.N. et al.: "Interleukin-1Receptor Antagonist in the Muckle-Wells Syndrome" N Engi J Med, Vol.348, No.25, 200306-19, pages 2583-2584. FORSTER A. et al.: "Neue Studien an der Rheumaklinik: Patienten (см. прод.) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 26.05.2008 (86) ...

ПРОТИВОРАКОВАЯ ТАРГЕТНАЯ ИММУНОТЕРАПИЯ С ПРИМЕНЕНИЕМ IL-12

Группа изобретений относится к противораковой иммунотерапии. Предложено применение нацеленного на опухоль IL-12 для комбинированной терапии с IL-7 для индукции и/или стимуляции иммунного ответа против рака у пациента, где рак - плотные опухоли или опухоли мышц, костей, нервной системы, хрящей, сухожилий, кровеносных сосудов и жировых или волокнистых тканей, и указанная индукция (стимуляция) вызывает старение раковых клеток или блокировку их роста, и/или ремиссию раковых клеток или раковой ткани до клеток или ткани происхождения, где IL-12 слит через N-конец своих субъединиц р40 и/или р35 с С-концом полностью человеческого антитела NHS76 или его биологически активного фрагмента, и где IL-7 ковалентно слит с тяжелой цепью иммуноглобулина или Fc-фрагментом тяжелой цепи иммуноглобулина; применение нацеленного на опухоль IL-12 для комбинированной терапии с IL-2 саркомы (вариант); набор того же назначения, включающий (а) полностью человеческое антитело NHS76, направленное на человеческий комплекс ДНК-гистон HI, представленный в опухолевом некрозе, и слитое через С-конец с N-концом субъединиц р40 и/или р35 IL-12, и (б) иммуномодулятор и/или иммунокомплементарный агент, представляющий собой IL-7, ковалентно слитый с тяжелой цепью иммуноглобулина или Fc-фрагментом тяжелой цепи иммуноглобулина, или представляющий собой IL-2 в комплексе с анти-IL-2-антителом (варианты). Технический результат: побуждаемая IL-12 иммунная система пациента не только убивает раковые клетки, но и использует альтернативные механизмы ослабления роста опухоли. 4 н. и 6 з.п. ф-лы, 8 ил., 13 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 689 160 C2 (51) МПК A61K 38/20 (2006.01) A61K 39/395 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 38/20 (2019.02); A61K 39/395 (2019.02); A61P 35/00 (2019.02); A61K 2123/00 (2019.02) (21)(22) Заявка: 2016136990, 18.02.2015 (24) Дата начала отсчета срока действия патента: Дата ...

НОВОЕ ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ИЛ-1 БЕТА

... 1. Лекарственное средство для лечения атеросклероза - антитело, которое включает антитело, связывающее IL-1 бета, где антитело содержит вариабельные домены как тяжелой (V), так и легкой цепи (V), в которых указанное связывающее IL-1 бета антитело содержит по меньшей мере один антигенсвязывающий сайт, включающийпервый домен, имеющий последовательность аминокислот, показанную в SEQ ID NO:1,и второй домен, имеющий последовательность аминокислот, показанную в SEQ ID NO:2, причем указанное антитело вводится парентерально в дозе 0,1-50 мг указанного антитела на кг веса тела пациента.2. Применение по п.1, где указанным антителом является ACZ885.3. Применение по п.1 или 2, при котором указанное антитело вводится в дозе 0,5-20 мг указанного антитела на кг веса тела пациента.4. Применение по п.1 или 2, при котором указанное антитело вводится в дозе 1-10 мг указанного антитела на кг веса тела пациента.5. Применение по п.1 или 2, где указанное антитело вводится один раз в неделю или реже.6. Применение ...

АНТИТЕЛА К ЧЕЛОВЕЧЕСКОМУ ИНТЕРЛЕЙКИНУ-2 И ИХ ПРИМЕНЕНИЕ

Настоящее изобретение относится к области иммунологии. Предложено анти-hIL-2 антитело или его антигенсвязывающий фрагмент, нуклеиновая кислота, рекомбинантный вектор, способ получения анти-hIL-2 антитела или его антигенсвязывающего фрагмента. Также рассмотрен комплекс для применения в минимизации экспансии клеток Treg и стимуляции Т-клеток CD8+ и клеток NK, композиция для применения при предотвращении или лечении рака. Кроме того, рассмотрена композиция для совместного введения для применения при лечении рака и композиция для применения при увеличении эффективности вакцины. Данное изобретение может найти дальнейшее применение в качестве противораковой терапии. 9 н. и 6 з.п. ф-лы, 10 ил., 8 табл., 7 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) (19) RU (11) (13) 2 745 451 C1 (51) МПК C07K 16/24 (2006.01) C12N 15/13 (2006.01) C12N 15/63 (2006.01) C12N 5/10 (2006.01) C12P 21/08 (2006.01) A61K 39/395 (2006.01) A61P 35/00 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 39/001156 (2021.01); A61K 39/3955 (2021.01); A61P 35/00 (2021.01); C07K 16/246 (2021.01); C07K 16/2818 (2021.01); A61K 2039/505 (2021.01); A61K 2039/507 (2021.01); A61K 2039/55533 (2021.01); A61K 2039/55561 (2021.01); C07K 2317/24 (2021.01); C07K 2317/33 (2021.01); C07K 2317/55 (2021.01); C07K 2317/565 (2021.01); C07K 2317/74 (2021.01); C07K 2317/76 (2021.01); C07K 2317/92 (2021.01) 2019137963, 25.05.2018 (24) Дата начала отсчета срока действия патента: 25.05.2018 25.03.2021 Приоритет(ы): (30) Конвенционный приоритет: 25.05.2017 KR 10-2017-0064815 (56) Список документов, цитированных в отчете о поиске: WO 2016/005950 A1, 14.01.2016. WO 2017/070561 A1, 27.04.2017. WO 2014/066834 A1, 01.05.2014. RU 2425054 C2, 27.07.2011. EA 13677 B1, 30.06.2010. (45) Опубликовано: 25.03.2021 Бюл. № 9 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 25.11.2019 (86) Заявка PCT: C 1 KR 2018/005955 (25.05.2018) (87) Публикация заявки PCT: 2 7 4 5 4 5 1 WO 2018/217058 (29 ...

ПРОТИВОРАКОВАЯ ТАРГЕТНАЯ ИММУНОТЕРАПИЯ С ПРИМЕНЕНИЕМ IL-12

HERSTELLUNG VON IMPSTOFFEN ZÜR VORBEUGUNG VON PATHOGENEN ZUSTÄNDEN EINER HIV RETROVIRALER INFEKTION

Compositions of protein complexes and methods of use thereof

USE OF POLYKLONALER ANTI-IL-2 ANTIBODIES FOR THE TREATMENT OF INSULIN-DEPENDENT DIABETES MELLITUS AND LUPUS ERYTHEMATOSUS

PRODUCTION OF IMPSTOFFEN ZÜR PREVENTION OF PATHOGENEN CONDITIONS OF A HIV OF RETROVIRALER INFECTION

PROCEDURE FOR THE DISTANCE OF N-TERMINAL ONE METHIONIN

STABLE PHARMACEUTICAL LIQUID FORMULATION OF IGG ANTIKÖRPERN

Engineered heterodimeric protein domains

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

Compositions and methods for the regulation of T regulatory cells using Tl1a-Ig fusion protein

Compositions comprising TL1 A-lg fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin). In some embodiments, provided here is an isolated or recombinant nucleic acid comprising a polynucleotide sequence which encodes a fusion protein, the fusion protein comprising (a) a first polypeptide comprising a polypeptide sequence that specifically binds to Tumor Necrosis Factor Receptor Superfamily, Member 25 (TNFRSF25), and (b) a second polypeptide comprising an immunoglobulin (Ig) polypeptide; or a complementary polynucleotide sequence thereof.

Combination therapy comprising a superagonistic antibody against interleukin-2 and a checkpoint blockade agent

The invention relates to a combination medicament comprising a human interleukin-2 (hIL-2)-specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25, and an immune checkpoint inhibitor agent. The hIL-2 antibody can be given without or with recombinant hIL-2 and is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (K ...

ANTIBODIES THAT BIND INTERLEUKIN-2 AND USES THEREOF

The present disclosure relates, in general, to human antibodies against human interleukin 2 (IL-2) and methods of use of such antibodies for modulating IL-2 activity and use in the treatment of conditions such as cancer, autoimmune disease, or infection.

MODULATING THE EFFECTS OF GAMMA-C-CYTOKINE SIGNALING FOR THE TREATMENT OF ALOPECIA AND ALOPECIA ASSOCIATED DISORDERS

The yc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as alopecia and alopecia associated disorders. Compositions, methods, and kits to modulate signaling by at least one yc-cytokine family member for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one alopecia related disorder are described.

INTERLEUKIN-2 MUTEINS FOR THE EXPANSION OF T-REGULATORY CELLS

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

METHOD FOR EXPANDING PRIMATE B CELLS SELECTIVELY IN IMMUNOCOMPROMISED MICE AND PRODUCING LARGE NUMBERS OF ANTIGEN-SPECIFIC B LYMPHOCYTES FOR THE PRODUCTION OF PRIMATE MONOCLONAL ANTIBODIES

The present invention relates to a method for reconstituting immunocompromised mice with primate cells, consisting of the following steps: (a) preparation of an immunocompromised mouse by administration of an antibody against the beta chain of the mouse interleukin 2 (IL-2) receptor, more particularly the monoclonal mouse TM-.beta.1 monoclonal antibody and/or gamma irradiation, (b) intraspleen injection of primate cells into the spleen of the pre-treated immunocompromised mouse of step (a), where these primate cells preferably originate from a primate donor and where this primate donor may have been immunised with a well-defined antigen. This method was found to be highly suitable for expanding primate B lymphocytes in an animal model in a rapid, as yet unequalled manner. Other embodiments of this invention relate to immunocompromised mice obtained by the aforesaid method and also the use thereof as animal models, primate B cell culture produced and primate monoclonal antibodies derived ...

CANCER-TARGETED IL-12 IMMUNOTHERAPY

The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and / or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and / or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases.

COMPOSITIONS AND METHODS FOR THE REGULATION OF T REGULATORY CELLS USING TL1A-IG FUSION PROTEIN

Compositions comprising TL1 A-lg fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin). In some embodiments, provided here is an isolated or recombinant nucleic acid comprising a polynucleotide sequence which encodes a fusion protein, the fusion protein comprising (a) a first polypeptide comprising a polypeptide sequence that specifically binds to Tumor Necrosis Factor Receptor Superfamily, Member 25 (TNFRSF25), and (b) a second polypeptide comprising an immunoglobulin (Ig) polypeptide; or a complementary polynucleotide sequence thereof.

METHOD FOR REMOVING N-TERMINAL METHIONINE

The present invention provides a method for chemically removing a N-terminal methionine residue selectively, specifically and efficiently from a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal. The method reacts a peptide or a salt thereof having an optionally oxidized methinine residue at its N-terminal with an .alpha.-diketone derivative, followed by hydrolysis.

METHOD FOR OBTAINING VACCINES FOR PREVENTING THE PATHOGENIC EFFECTS RELATED TO A RETROVIRAL INFECTION

Pour obtenir un vaccin contre les effets pathogènes associés à l'infection d'un hôte par un rétrovirus, dans le cas où les cellules cibles du rétrovirus possèdent un récepteur membranaire pour une protéine de l'hôte et où l'infection virale induit une réponse immunitaire dirigée à la fois contre une protéine d'enveloppe du virus et contre une protéine de l'hôte, on prépare un agent vaccinal à base d'un polypeptide comprenant un fragment d'une zone immunodominante et conservée de la protéine d'enveloppe du rétrovirus, sous une forme modifiée telle que l'agent vaccinal induit une réponse immunitaire dirigée contre la protéine d'enveloppe et non contre la protéine de l'hôte.

Methods and compositions for promoting hair growth

Hybridomas and monoclonal antibodies to human IL-2

Certain hybridomas preparing monoclonal antibodies to human interleukin-2 (IL-2) which do not cross react with rator mouse IL-2 are disclosed. The secreted monoclonal antibody can be used in immunoassays for human IL-2.

CHIMERIC ANTIGEN RECEPTOR (CAR)-T CELLS

The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating, and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention is also concerned with methods for expansion of MAIT cells in vitro.

IMMUNOMODULATING POLYMERS

Methods and products for inducing IL-2 secretion, inducing IL-10 secretion, activating T cells, suppressing IgG antibody response to specific antigen, promoting allograft survival, reducing postoperative surgical adhesion formation, and protecting against abscess formation associated with surgery, trauma or diseases that predispose the host to abscess formation are provided. The methods of the invention are accomplished using an immunomodulator which is a polymer having at least two repeating charge motifs separated by at least a certain minimum distance.

ANTI-INTERLOYKIN-DIMONOCLONAL ANTIBODY

СПОСОБ ЛЕЧЕНИЯ ПАТОЛОГИЧЕСКОГО СИНДРОМА И ЛЕКАРСТВЕННОЕ СРЕДСТВО

FIELD: medicine, therapy, pharmacy. SUBSTANCE: invention relates to treatment of patients with different diseases and involves administration of activated forms of superlow doses of antibodies raised to antigen. The latter takes part in mechanisms of development of pathological process and this substance can be both endogenous factors inducing disease and medicinal agents used for treatment of patients with this disease. Activated forms of antibodies are prepared by homeopathic technology. Invention proposes the medicinal agent containing these antibodies. Invention provides the reproduction of antigen activity in modified form promoting to reduction of pathological process and without adverse effects of treatment. EFFECT: improved method of treatment. 12 cl 68 Ес ПЧ сэ (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2181 297' 5 МК’ А 64 К 39/395, А 61 Р 37/00 13) С2 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 2000115594/14, 20.06.2000 (24) Дата начала действия патента: 20.06.2000 (46) Дата публикации: 20.04.2002 (56) Ссылки: КЦ 98109384 А1, 10.03.2000. КУ (71) Заявитель: Чернова Ольга Вячеславовна (КИ) (72) Изобретатель: Эпштейн О.И. (КЦ), Колядко Тамара Михайловна (ЦА), Штарк М.Б. (КУ) 2122863 СЛ, 10.12.1998. (73) Патентообладатель: сч Эпштейн Олег Ильич (КИ) © (98) Адрес для переписки: 103009, Москва, Средний Кисловский пер., ГО, кв.26, А.С.Попову к (54) СПОСОБ ЛЕЧЕНИЯ ПАТОЛОГИЧЕСКОГО СИНДРОМА И ЛЕКАРСТВЕННОЕ СРЕДСТВО © (57) Активированные формы антител готовят по м Изобретение относится к медицине, в гомеопатической технологии. Предложено частности к терапии различных заболеваний. лекарственное средство, содержащее такие \— Для этого вводят активированные формы антитела. Изобретение обеспечивает ©о сверхмалых доз антител к антигену-веществу, воспроизведение активности антигена в участвующему в механизмах развития модифицированном виде, способствующем = патологического процесса. К такому веществу редукции патологического ...

HYBRIDOMA ANTIBODY WHICH INHIBITS INTERLEUKIN-2 ACTIVITY AND ITS USE AS A REAGENT FOR INTERLEUKIN-2 DETECTION, THE PRODUCTION OF SAID ANTIBODY, A PROCESS FOR PRODUCING HYBRID ANTI-INTERLEUKIN-2 ANTIBODY PRODUCING CELLS, AND SUCH CELLS

IL-2 compositions and methods of use thereof

Provided are activatable proproteins comprising at least two separate polypeptide chains, the first comprising IL-2 fused to a masking moiety and the second comprising an IL-2 binding protein fused to a masking moiety, and related pharmaceutical compositions and methods of use thereof.

Immune-stimulating humanized monoclonal antibodies against human interleukin-2, and fusion proteins thereof

The present invention relates to antibodies binding to human interleukin-2 (hIL-2). The invention more specifically relates to humanized antibodies specifically binding a particular epitope of hIL-2 and, when bound to this epitope, displaying a unique capability of inhibiting binding of hIL-2 to CD25.

PREVENTION AND TREATMENT OF AUTOIMMUNE DISEASE WITH LUMINALLY ADMINISTERED POLYCLONAL ANTIBODIES

The prevention and treatment of autoimmune disease in humans (as well as other animals) is described through the use of ligands directed to cytokines. Antibodies and receptors to the proinflammatory cytokines IL-2, TNF, IL-12 and IFN-gamma are employed (along with other ligands to such cytokines). Such ligands administered luminally are effective (as demonstrated in two experimental models of autoimmune disease) at delaying the onset of autoimmune disease.

ANTI-IL2 ANTIBODIES

The invention relates to a humanized monoclonal antibody or fragment thereof which specifically binds to human interleukin-2 (IL2), wherein said humanized monoclonal antibody neutralizes the activity of human IL2 by binding to said human IL2 prior to, during, and/or subsequent to the binding of said human IL2 to the human IL2-receptor, and wherein the light chain variable region of said humanized monoclonal antibody comprises in its second framework region the contiguous amino acid sequence KAPKA at amino acid positions 42-46.

MULTISPECIFIC ANTIBODY MOLECULES COMPRISING LAMBDA AND KAPPA LIGHT CHAINS

Multispecific, e.g., bispecific, antibody molecules that include a kappa light chain polypeptide and one lambda light chain polypeptide, and methods of making and using the multispecific antibody molecules, are disclosed.

DUAL OX40 AGONIST/IL-2 CANCER THERAPY METHODS

OX40 is a potent immune stimulating target. Provided herein is a method of treating cancer, which includes administering to a subject in need of treatment an OX40 agonist and a common gamma chain (yc) cytokine or an active fragment, variant, analog, or derivative thereof In certain aspects the common gamma chain (yc) cytokine is interleukin-2 (IL-2) or an active fragment, variant, analog, or derivative thereof. Combined treatment with an agonist anti-OX40 mAb and IL-2 synergized to augment tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8+ T cells.

ANTI-IL2 ANTIBODIES

The invention relates to a humanized monoclonal antibody or fragment thereof which specifically binds to human interleukin-2 (IL2), wherein said humanized monoclonal antibody neutralizes the activity of human IL2 by binding to said human IL2 prior to, during, and/or subsequent to the binding of said human IL2 to the human IL2-receptor, and wherein the light chain variable region of said humanized monoclonal antibody comprises in its second framework region the contiguous amino acid sequence KAPKA at amino acid positions 42-46. © KIPO & WIPO 2008 ...

ANTICUERPOS ANTI-SIRPA (PROTEÍNA REGULADORA DE SEÑALES a) Y MÉTODOS DE USO DE LOS MISMOS

La presente divulgación se dirige generalmente a composiciones que incluyen anticuerpos, por ejemplo, fragmentos de anticuerpos, anticuerpos monoclonales, etc., que específicamente se unen a un polipéptido SIRPA, por ejemplo, un SIRPA de mamíferos o SIRPA de humano, y a la utilización de dichas composiciones en la prevención, reducción del riesgo, o tratamiento de un individuo que lo necesita.

ANTIBODIES TO HUMAN INTERLEUKIN-2 INDUCED BY SYNTHETIC POLYPEPTIDES

Chemically synthesized polypeptides containing about 6 to about 40 amino acid residues having amino acid residue sequences that substantially correspond to the amino acid residue sequences of antigenic determinants of interleukin-2, (P81, P83, etc.) when administered alone or as polymers or as conjugates bound to carriers, induce the production of antibodies of predetermined specificities. The polypeptides and the antibodies produced thereto can be used in diagnostic systems to measure the presence and amount of interleukin-2 and interleukin-2 cell surface receptors or binding sites in an assayed sample.

METHOD FOR OBTAINING VACCINES FOR PREVENTING THE PATHOGENIC EFFECTS RELATED TO A RETROVIRAL INFECTION

The invention concerns a method for obtaining a vaccine against the pathogenic effects related to infection of a host by a retrovirus, in the event that the target cells of the retrovirus have a membrane receptor for a protein of the host and the viral infection induces an immune response directed both against an envelope protein of the virus and against a protein of the host. The method consists in preparing a vaccine agent based on a polypeptide comprising a fragment of an immunodominant and preserved zone of the retrovirus envelope protein, in a modified form such that the vaccine agent induces an immune response directed against the envelope protein and not against the host protein.

INHIBITION OF IL-2 PRODUCTION

An object is to find a substance which inhibits IL-2 production. 115.-. (canceled)17. The method according to claim 16 , wherein the compound represented by the formula (I) is a compound whereinA represents a lower alkylene group;{'sup': '1', 'Rrepresents a halogen atom;'}{'sup': '2', 'Rrepresents a lower alkoxy group;'}{'sup': '3', 'Rrepresents a lower alkyl group; and'}{'sup': '4', 'Rrepresents a lower alkyl group substituted by a hydroxyl group, a lower alkyl group substituted by a lower alkoxy group, a lower alkyl group substituted by a lower alkoxy group which is substituted by a lower alkoxy group or a lower alkyl group substituted by an acetoxy group.'}18. The method according to claim 16 , wherein the compound represented by the formula (I) is a compound whereA represents trimethylene group or 1-methyltrimethylene group;{'sup': '1', 'Rrepresents chlorine atom;'}{'sup': '2', 'Rrepresents methoxy group;'}{'sup': '3', 'Rrepresents isopropyl group; and'}{'sup': '4', 'Rrepresents 2-hydroxyethyl group, 2-methoxyethyl group, 2-ethoxyethyl group, 2-(methoxymethoxy)ethyl group or 2-acetoxyethyl group.'}19. The method according to claim 16 , wherein the compound represented by the formula (I) is (+)-3-acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline claim 16 , (±)-3-acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline claim 16 , (+)-3-acetyl-6-chloro-2-[2-(3-(N-(2-hydroxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline or (+)-3-acetyl-6-chloro-2-[2-(3-(N-isopropyl-N-(2-methoxyethyl)amino)propoxy)-5-methoxyphenyl]benzothiazoline.20. The method of any one of to claim 16 , wherein the pharmaceutically acceptable salt of the compound represented by the formula (I) is a (−)-O claim 16 ,O′-diacetyl-L-tartaric acid salt or a hydrochloric acid salt. The present invention relates to an IL-2 production inhibitor or a prophylactic or therapeutic agent of IL-2 ...

Methods of treating arthritis using IL-1 binding molecules

This invention relates to methods employing IL-1β-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1β ligand-IL-1 receptor interaction, IL-1β antibodies or IL-1 receptor antibodies, e.g. IL-1β binding molecules as described herein, e.g. antibodies disclosed herein, e.g. IL-1β binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1β ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

De Novo Design of Potent and Selective Interleukin Mimetics

De novo designed polypeptides that bind to IL-2 receptor βνc heterodimer (IL-2Rβνc), IL-4 receptor ανc heterodimer (IL-4Rανc), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.

АНТИТЕЛА ПРОТИВ IL2

Гуманизированное моноклональное антитело и его активный фрагмент по изобретению нейтрализует активность человеческого IL2 путем связывания с указанным человеческим IL2 до, во время и/или после связывания указанного человеческого IL2 с человеческим рецептором IL2. Вариабельная область легкой цепи указанного антитела содержит в ее второй каркасной области последовательность смежных аминокислот КАРКА и дополнительно содержит в CDR1-CDR3 областях аминокислотные последовательности, представленные в SEQ ID NO 1-3, раскрытые в описании, а вариабельная область тяжелой цепи содержит в CDR1-CDR3 областях аминокислотные последовательности, представленные в SEQ ID NO 4-6, раскрытые в описании. В изобретении описана полинуклеотидная молекула, кодирующая антитело по изобретению или его активный фрагмент, фармацевтическая композиция на основе указанного антитела или его активного фрагмента, обладающая нейтрализующим действием в отношении человеческого IL2, а также применение указанного антитела или его ...

НОВОЕ ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ИЛ-1β

FIELD: medicine, pharmaceutics. SUBSTANCE: group of inventions relates to the field of medicine. In particular the group of inventions relates to the application of an antibody to IL-1β for the treatment and prevention of Familial Mediterranean fever, for the creation of a medication for the treatment of Familial Mediterranean fever, as well as to the pharmaceutical composition. EFFECT: group of inventions is effective in the prevention and treatment of Familial Mediterranean fever. 11 cl, 3 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК A61K 39/395 (13) 2 571 563 C2 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2012133522/15, 06.08.2012 (24) Дата начала отсчета срока действия патента: 24.10.2006 Приоритет(ы): (30) Конвенционный приоритет: (73) Патентообладатель(и): НОВАРТИС АГ (CH) 2 5 7 1 5 6 3 R U (56) Список документов, цитированных в отчете о поиске: HAWKINS ET AL. "INTERLEUKIN-1RECEPTOR ANTAGONIST IN THE MUCKLEWELLS SYNDROME" NEW ENGLAND JOURNAL OF MEDICINE, MASSACHUSETTS MEDICAL SOCIETY, BOSTON, MA, US, vol. 348, no. 25, 19 June 2003 (2003-06-19), pp. 25832584. WO03010282 A2, 06.02.2003. WO0153353 A2, 26.07.2001. Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной (54) НОВОЕ ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ИЛ-1β (57) Реферат: Группа изобретений относится к области средиземноморской лихорадки, а также медицины. Более подробно группа изобретений фармацевтической композиции. Группа относится к применению антитела к ИЛ-1β для изобретений эффективна в предупреждении и лечения и предупреждения семейной лечении семейной средиземноморской лихорадки. средиземноморской лихорадки, для создания 3 н. и 8 з.п. ф-лы, 3 пр. лекарственного средства для лечения семейной Стр.: 1 C 2 C 2 (45) Опубликовано: 20.12.2015 Бюл. № 35 2 5 7 1 5 6 3 (43) Дата публикации заявки: 20.02.2014 Бюл. № 5 R U 26.10.2005 US 60/730,435; 02.12.2005 US 60/742, ...

НОВОЕ ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ИЛ-1β

... 1. Применение ИЛ-1β-соединений для изготовления лекарственного препарата для лечения аутовоспалительного синдрома. ! 2. Применение по п.1, в котором ИЛ-β-соединения представляют собой ИЛ-1β-связывающие молекулы, которые включают антигенсвязывающий центр, содержащий по меньшей мере один вариабельный домен тяжелой цепи иммуноглобулина (VH), содержащий следующие друг за другом гипервариабельные участки CDR1, CDR2 и CDR3, причем указанный CDR1 имеет последовательность аминокислот Val-Tyr-Gly-Met-Asn, указанный CDR2 имеет последовательность аминокислот Ile-Ile-Trp-Tyr-Asp-Gly-Asp-Asn-Gln-Tyr-Tyr-Ala-Asp-Ser-Val-Lys-Gly и указанный CDR3 имеет последовательность аминокислот Asp-Leu-Arg-Thr-Gly-Pro, и их непосредственные эквиваленты. ! 3. Применение по п.1, в котором ИЛ-β-соединения представляют собой ИЛ-1β-связывающие молекулы, которые включают вариабельные домены как тяжелой (VH), так и легкой (VL) цепи, в которых указанная ИЛ-1β-связывающая молекула содержит по меньшей мере один антигенсвязывающий ...

ИММУНОМОДУЛИРУЮЩИЕ СПОСОБЫ И СИСТЕМЫ ДЛЯ ЛЕЧЕНИЯ И/ИЛИ ПРЕДОТВРАЩЕНИЯ ГИПЕРТЕНЗИЙ

1. Способ лечения и/или предотвращения гипертензии и/или ассоциированного с ней состояния у индивидуума, где способ включает в себявведение индивидууму эффективного количества одного или нескольких из иммуногенных фрагментов ApoB-100 или их иммуногенно активной части, где иммуногенный фрагмент содержит один из SEQ ID NO: 1-302, где один или несколько иммуногенных фрагментов или их иммуногенно активные части ассоциированы с уменьшением атеросклероза.2. Способ по п.1, где один или несколько иммуногенных фрагментов содержат один или несколько пептидов, где каждый содержит один из SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO:25, SEQ ID NO:45, SEQ ID NO:74, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 105, SEQ ID NO: 129, SEQ ID NO: 143, SEQ ID NO: 148, SEQ ID NO: 210 или SEQ ID NO:301.3. Способ по п.1, где один или несколько иммуногенных фрагментов содержат один или несколько пептидов, где каждый содержит один из SEQ ID NO: 2, SEQ ID NO: 11, SEQ ID NO: 45, SEQ ID NO: 74, SEQ ID NO: 102, SEQ ID NO: 148 или SEQ ID NO:210.4. Способ по п.1, где один или несколько иммуногенных фрагментов содержат пептид, имеющий SEQ ID NO: 143, и пептид, имеющий SEQ ID NO: 210.5. Способ по п.1, где один или несколько иммуногенных фрагментов содержат пептид, имеющий SEQ ID NO: 11, пептид, имеющий SEQ ID NO: 25, и пептид, имеющий SEQ ID NO: 74.6. Способ по п.1, где один или несколько иммуногенных фрагментов содержат пептид, имеющий SEQ ID NO: 2.7. Способ по п.1, где один или несколько иммуногенных фрагментов содержат пептид, имеющий SEQ ID NO: 45.8. Способ по п.1, где один или несколько иммуногенных фрагментов содержат пептид, имеющий SEQ ID NO: 210.9. Способ по любому из пп. 1-8, где индивидуум представляет собой человека, и концентрация составляет между приблизительно 100 мкг и приблизительно менее 1 мг.10. Способ по любому из пп. 1-8, г РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК A61K 39/00 (13) 2013 126 626 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ...

Methods and arrays for use in the same

Modulation of T cell cytotoxicity and related therapy

Curing method for pathologic syndrome and a medicinal preparation

Cancer-targeted IL-12 immunotherapy

The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and / or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and / or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases.

Interleukin-2 muteins for the expansion of T-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Humanized CC chemokine receptor 4 (CCR4) antibodies and methods of use thereof

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4- IgG 1 and recognizes the same epi-tope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.

Prevention and treatment of autoimmune disease with luminally administered polyclonal antibodies

METHOD FOR OBTAINING VACCINES FOR PREVENTING THE PATHOGENIC EFFECTS RELATED TO A RETROVIRAL INFECTION

Pour obtenir un vaccin contre les effets pathogènes associés à l'infection d'un hôte par un rétrovirus, dans le cas où les cellules cibles du rétrovirus possèdent un récepteur membranaire pour une protéine de l'hôte et où l'infection virale induit une réponse immunitaire dirigée à la fois contre une protéine d'enveloppe du virus et contre une protéine de l'hôte, on prépare un agent vaccinal à base d'un polypeptide comprenant un fragment d'une zone immunodominante et conservée de la protéine d'enveloppe du rétrovirus, sous une forme modifiée telle que l'agent vaccinal induit une réponse immunitaire dirigée contre la protéine d'enveloppe et non contre la protéine de l'hôte.

METHODS AND ARRAYS FOR USE IN THE SAME

The invention provides a method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of: (a) providing a sample to be tested from the individual; and (b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1; wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual. The invention also provides arrays and kits for use in the same.

METHODS FOR IMPROVING IMMUNE FUNCTION AND METHODS FOR PREVENTION OR TREATMENT OF DISEASE IN A MAMMALIAN SUBJECT

STABLE AQUEOUS PHARMACEUTICAL FORMULATIONS OF DACLIZUMAB ANTIBODIES

... ²²²This invention is directed to a stable liquid pharmaceutical formulation ²comprising a high concentration, e.g. 50 mg/ml or more, of antibody in about ²20-60 mM succinate buffer or 30-70 mM histidine buffer, having pH from about ²pH 5.5 to about pH 6.5, about 0.01-0.1 % polysorbate, and a tonicity modifier ²that contributes to the isotonicity of the formulation. This liquid ²formulation is stable at refrigerated temperature (2-8~C) for at least 1 year, ²and preferably 2 years. This liquid formulation is suitable for subcutaneous ²injection. This invention is exemplified by Daclizumab, a humanized anti-IL-2 ²receptor monoclonal antibody; HAIL-12, a humanized anti-IL-12 monoclonal ²antibody; HuEP5C7, a humanized anti-L selectin monoclonal antibody; and ²Flintozumab, a humanized anti-gamma interferon monoclonal antibody.² ...

METHODS FOR THE PRODUCTION OF PROTEINS WITH A DESIRED FUNCTION

The present invention provides a method for producing proteins with a desire d function, generally comprising the steps of (a) providing a population of antibody-forming cells suspected of containing at least one cell capable of producing an antibody exhibiting a desired function; (b) suspending the population of antibody- forming cells in a medium the medium having an indi- cator system incorporated therein, the indicator system also being capable o f indicating the presence and location of a cell which forms antibodies exhibiting the desired function; (c) identifying a cell forming an antibody exhibiting the desired function; (d) isolating the identified antibody-forming cell from the medium; (e) determining the amino acid sequence of the variable region or a portion thereof which confers the desired function of the antibody produce d by the isolated antibody-forming cell; and (f) syn- thesizing a protein with a desired function, the protein containing the amin o acid sequence of the ...

Immunomodulatory Methods and Systems for Treatment and/or Prevention of Hypertension

Immunomodulatory agents, T cell, compositions, methods and systems for treating and/or preventing hypertension and/or a condition associated thereto in an individual.

HUMANIZED CC CHEMOKINE RECEPTOR 4 (CCR4) ANTIBODIES AND METHODS OF USE THEREOF

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. 1. An isolated humanized monoclonal antibody that binds to the human CC chemokine receptor 4 (CCR4) and has an IgG4 heavy chain constant region.2. The antibody of claim 1 , wherein{'sub': H', 'L, 'a. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 2 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 4;'}{'sub': H', 'L, 'b. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 16 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 18;'}{'sub': H', 'L, 'c. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 20 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 22;'}{'sub': H', 'L, 'd. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 24 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 25;'}{'sub': H', 'L, 'e. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 28 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 30'}{'sub': H', 'L, 'claim-text': 'the heavy chain constant region comprises SEQ ID NO: 6 or SEQ ID: 8;', 'f. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 44 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 46; and'}3. The antibody of claim 2 , wherein said antibody ...

COMBINATION THERAPY COMPRISING A SUPERAGONISTIC ANTIBODY AGAINST INTERLEUKIN-2 AND A CHECKPOINT BLOCKADE AGENT

The invention relates to a combination medicament comprising a human interleukin-2 (hIL-2)-specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25, and an immune checkpoint inhibitor agent. The hIL-2 antibody can be given without or with recombinant hIL-2 and is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (K)≤7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (K)≤1×10sand/or the antibody displays no measurable cross-reactivity to murine IL-2. 1. A combination medicament comprising i. the variable chain of the mAb comprises an amino acid sequence having an identity of ≥85%, ≥90%, ≥95%, or ≥99% compared to SEQ ID NO 005 or SEQ ID NO 006;', {'sub': 'D', 'ii. the binding to hIL-2 is characterized by a dissociation constant (K) ≤7.5 nmol/L, ≤5 nmol/L, ≤3 nmol/L, ≤2 nmol/L or ≤1.5 nmol/L;'}, {'sub': 'off', 'sup': 4', '−1', '5', '−1', '5', '−1', '5', '−1', '−5', '−1', '−5', '−1, 'iii. the binding to hIL-2 is characterized by an off-rate (K)≤1×10s, ≤8×10s, ≤6×10s, ≤4×10s, ≤3×10sor ≤2.1×10s;'}, 'iv. the antibody or antigen binding fragment thereof binds to a specific human interleukin-2 (hIL-2) epitope which comprises the amino acids K52, P54, K55, T57, R58, T61, F62, K63, Q94, and K96 of hIL-2; and/or', 'v. the antibody displays no measurable cross-reactivity to murine IL-2., 'a. a human interleukin-2 (hIL-2)-specific monoclonal antibody (mAb), or antigen binding fragment thereof, wherein binding of said antibody to hIL-2 inhibits binding of hIL-2 to CD25, and the antibody is characterized by any one of the parameters i. an inhibitor of interaction of CTLA-4 with CD80 or CD86,', 'ii. an inhibitor of PD-1/PD-L1 interaction, and', 'iii. a ligand of TIM-3., 'b. an immune checkpoint inhibitor agent selected from'}2. The ...

IMMUNE-STIMULATING HUMANIZED MONOCLONAL ANTIBODIES AGAINST HUMAN INTERLEUKIN-2, AND FUSION PROTEINS THEREOF

The present invention relates to antibodies binding to human interleukin-2 (hIL-2). The invention more specifically relates to humanized antibodies specifically binding a particular epitope of hIL-2 and, when bound to this epitope, displaying a unique capability of inhibiting binding of hIL-2 to CD25. 1. An isolated antibody , or antigen-binding portion thereof , which binds human interleukin-2 (IL-2) according to SEQ ID NO: 109 , wherein said antibody or antigen-binding portion thereof comprises a light chain variable region comprising LCDR1 , a LCDR2 and a LCDR3 and a heavy chain variable region comprising a HCDR1 , a HCDR2 and a HCDR3 and wherein the LCDR1 comprises SEQ ID NO: 122; wherein LCDR2 comprises SEQ ID NO: 123; wherein LCDR3 comprises SEQ ID NO: 21; wherein HCDR1 comprises SEQ ID NO: 119; wherein HCDR2 comprises SEQ ID NO: 120; and wherein HCDR3 comprises SEQ ID NO: 121.2. The isolated antibody or antigen-binding portion thereof according to claim 1 , wherein said antibody or antigen-binding portion thereof comprises a light variable region comprising a:LCDR1 selected from the group consisting of SEQ ID NO: 19, SEQ ID NO: 31, SEQ ID NO: 69, SEQ ID NO: 72, SEQ ID NO: 86 and SEQ ID NO: 90;LCDR2 selected from the group consisting of SEQ ID NO: 20 and SEQ ID NO: 32;LCDR3 as set forth in SEQ ID NO: 21, anda heavy variable region comprising a:HCDR1 selected from the group consisting of SEQ ID NO: 4, and SEQ ID NO: 13;HCDR2 selected from the group consisting of SEQ ID NO: 2, and SEQ ID NO: 12; andHCDR3 selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 36, SEQ ID NO: 39, SEQ ID NO: 42, and SEQ ID NO: 45.3. The isolated antibody or antigen-binding portion thereof according to claim 1 , wherein theLCDR1, LCDR2 and LCDR3 are SEQ ID NO: 19, 20 and 21, respectively and the HCDR1, HCDR2 and HCDR3 are SEQ ID NO: 4, 2 and 3, respectively; orLCDR1, LCDR2 and LCDR3 are SEQ ID NO: 31, 32 and 21, respectively and the HCDR1, HCDR2 and HCDR3 are SEQ ID NO: 4, 2 ...

INTERLEUKIN-2 MUTEINS FOR THE EXPANSION OF T-REGULATORY CELLS

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention. 1. A human interleukin-2 (IL-2) mutein comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:1 , wherein said IL-2 mutein has at least one mutation selected from L12G , L12K , L12Q , L12S , Q13G , E15A , E15G , E15S , H16A , H16D , H16G , H16K , H16M , H16N , H16R , H16S , H16T , H16V , H16Y , L9A , L19D , L19E , L19G , L9N , L19R , L19S , L19T , L19V , D20A , D20E , D20F , D20G , D20T , D20W , M23R , R81A , R81G , R81S , R81T , D84A , D84E , D84G , D84I , D84M , D84Q , D84R , D84S , D84T , S87R , N88A , N88D , N88E , N88F , N88G , N88M , N88R , N88S , N88V , N88W , V91D , V91E , V91G , V91S , I92K , I92R , and E95G and preferentially stimulates T regulatory cells relative to other T cells or NK cells , both in in vitro assays and in humanized mice (NSG mice reconstituted with CD34+ hematopoietic stem cells).2. (canceled)3. (canceled)4. The human IL-2 mutein of further comprising a mutation at C125A.5. (canceled)6. An Fc-fusion protein comprising an Fc and the human IL-2 mutein of .7. (canceled)8. The Fc-fusion protein of claim 7 , wherein the human IgG1 Fc comprises one or more mutations altering effector function of said Fc.9. The Fc-fusion protein of claim 8 , wherein the human IgG1 comprises a substitution at N297.10. The Fc-fusion protein of claim 9 , wherein the substitution at N297 is ...

INTERLEUKIN-2 AGENTS AND USES THEREOF

IL-2 agents that comprise IL-2 variants are disclosed as well as methods, compositions, and uses thereof. The IL-2 agents described herein can be used to treat and/or prevent various disorders and conditions. 1. An interleukin-2 (IL-2) variant , comprising:(i) the amino acid substitution H16L or H16N, and/or the amino acid substitution I92S, and(ii) the amino acid substitutions V69A, Q74P, and C125S,corresponding to human IL-2 (SEQ ID NO: 1031).2. The IL-2 variant of claim 1 , further comprising the amino acid substitution T3A.3. The IL-2 variant of claim 1 , comprising the amino acid sequence of any of SEQ ID NOs: 4 claim 1 , 5 claim 1 , 11 claim 1 , 1000 claim 1 , 1001 claim 1 , or 1002 claim 1 , an amino acid sequence that is at least 95% identical thereto or differs by no more than 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 amino acids therefrom claim 1 , or a functional fragment thereof.4. The IL-2 variant of claim 1 , which selectively stimulates regulatory T cells (Tregs).5. An IL-2 fusion protein comprising the IL-2 variant of .6. The IL-2 fusion protein of claim 5 , further comprising an Fc region.7. The IL-2 fusion protein of claim 6 , wherein the Fc region comprises an Fc region of IgG1 allotype m3 comprising an N297G substitution according to EU numbering.8. The IL-2 fusion protein of claim 6 , wherein the Fc region comprises the amino acid sequence of SEQ ID NO: 1003 claim 6 , or an amino acid sequence that is at least 95% identical thereto or differs by no more than 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 claim 6 , 6 claim 6 , 7 claim 6 , 8 claim 6 , 9 claim 6 , or 10 amino acids therefrom claim 6 , or a functional fragment thereof.9. The IL-2 fusion protein of claim 6 , wherein the Fc region is fused to the C-terminus of the IL-2 variant.10. The IL-2 fusion protein of claim 6 , further comprising a linker.11. The IL-2 fusion protein of claim 10 , wherein the linker comprises (GS)(SEQ ID NO: 48).12. The IL-2 fusion protein of claim ...

COMPOSITIONS OF PROTEIN COMPLEXES AND METHODS OF USE THEREOF

Provided herein are protein complexes comprising a sensor domain and a therapeutic domain linked by a linker, and methods of use thereof. In aspects of the present disclosure, activity of the therapeutic domain comprises a dependence on sensor domain binding to target markers. 1. A pharmaceutical composition comprising a complex and a pharmaceutically acceptable excipient , wherein the complex comprises:a) a therapeutic domain; andb) a sensor domain,wherein:the therapeutic domain is linked to the sensor domain by a linker,the sensor domain is configured to bind the therapeutic domain and a marker; andwhen the sensor domain binds to the marker, the sensor domain is configured not to bind the therapeutic domain and the therapeutic domain is configured to bind to its receptor.2. The pharmaceutical composition of claim 1 , wherein when the sensor domain binds to the marker claim 1 , the therapeutic domain is blocked from binding the sensor domain and the therapeutic domain is able to bind to its receptor.3. The pharmaceutical composition of claim 1 , wherein when the therapeutic domain binds to the sensor domain claim 1 , the activity of the therapeutic domain is reduced.4. The pharmaceutical composition of claim 1 , wherein an affinity of the sensor domain for the therapeutic domain comprises a condition dependence.5. The pharmaceutical composition of claim 4 , wherein the condition dependence is selected from the group consisting of pH claim 4 , temperature claim 4 , salinity claim 4 , and osmolarity.6. The pharmaceutical composition of claim 1 , wherein an affinity of the sensor domain for the marker is at least 2 times greater than an affinity of the sensor domain for the therapeutic domain.7. The pharmaceutical composition of claim 1 , wherein an affinity of the sensor domain for the marker is at least 100 times greater than an affinity of the sensor domain for the therapeutic domain.8. The pharmaceutical composition of claim 1 , wherein the sensor domain comprises ...

METHODS AND ARRAYS FOR USE IN THE SAME

The invention provides a method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of: (a) providing a sample to be tested from the individual; and (b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1; wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual. The invention also provides arrays and kits for use in the same. 1. A method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of:a) providing a sample to be tested from the individual;b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1;wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual.2. The method according to further comprising or consisting of the steps of:c) providing one or more control sample from an individual not afflicted with prostate cancer;d) determining a biomarker signature of the control sample by measuring the expression in the control sample of the one or more biomarkers measured in step (b);wherein the one or more prostate cancer-associated disease state is identified in the event that the expression in the test sample of the one or more biomarkers measured in step (b) is different from the expression in the control sample of the one or more biomarkers measured in step (d).3. The method according to or further comprising or consisting of the steps of:e) providing a control sample from an individual afflicted with prostate cancer;f) determining ...

Inhibition of il-2 production

An object is to find a substance which inhibits IL-2 production. IL-2 production can be inhibited by a compound represented by the following formula (I): wherein R 1 to R 4 and A are as defined in the present specification, or a pharmaceutically acceptable salt thereof.

METHODS FOR THE DIAGNOSTIC OF AN AUTOIMMUNE DISEASE

An in vitro method for determining whether a patient has, or is at risk of having or developing an autoimmune disease or for assessing the severity or predicting the outcome of an autoimmune disease, comprising a step of detecting or quantifying in a biological sample obtained from said patient an immune anti-IL2 response, peptides specifically recognised by anti-IL2 antibodies or IL-2-specific T cells of T1D, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and autoimmune polymyositis patients, and pharmaceutical compositions. 1. An in vitro method for determining whether a patient has , or is at risk , of having or developing an autoimmune disease or for assessing the severity or predicting the outcome of an autoimmune disease , wherein said in vitro method comprises a step of detecting or quantifying , in a biological sample obtained from said patient , an immune anti-IL-2 response.2. The in vitro method according to claim 1 , wherein immune anti-IL2 response is evidenced by the detection or quantification of one or more of:B cells producing anti-IL-2 AutoAbs;anti-IL-2 antibodies; andIL-2-specific T-cells.3. The in vitro method according to claim 2 , wherein immune anti-IL2 response is evidenced by the detection or quantification of B cells producing anti-IL-2 AutoAbs or anti-IL-2 antibodies claim 2 , wherein the AutoAbs are neutralizing anti-IL-2 AutoAbs.4. The in vitro method according to claim 1 , wherein the autoimmune disease is selected from the group consisting of type 1 diabetes (T1D) claim 1 , systemic lupus erythematosus (SLE) claim 1 , rheumatoid arthritis (RA) claim 1 , Sjögren's syndrome (SJO) and autoimmune polymyositis (JO1).5. The in vitro method according to claim 1 , wherein the method is a method for determining whether a patient has claim 1 , or is at risk of having or developing claim 1 , an autoimmune disease.6. The in vitro method according to claim 1 , wherein the method is a method for assessing the severity of an ...

METHODS FOR THE DIAGNOSTIC OF AN AUTOIMMUNE DISEASE

An in vitro method for determining whether a patient has, or is at risk of having or developing an autoimmune disease or for assessing the severity or predicting the outcome of an autoimmune disease, comprising a step of detecting or quantifying in a biological sample obtained from said patient an immune anti-IL2 response, peptides specifically recognised by anti-1L2 antibodies or IL-2-specific T cells of T1D, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and autoimmune polymyositis patients, and pharmaceutical compositions. 115-. (canceled)16. An in vitro method for determining whether a patient has , or is at risk , of having or developing an autoimmune disease or for assessing the severity or predicting the outcome of an autoimmune disease , wherein said in vitro method comprises a step of detecting or quantifying , in a biological sample obtained from said patient , an immune anti-IL-2 response.17. The in vitro method according to claim 16 , wherein immune anti-IL2 response is evidenced by the detection or quantification of one or more of:B cells producing anti-IL-2 AutoAbs;anti-IL-2 antibodies; andIL-2-specific T-cells.18. The in vitro method according to claim 17 , wherein immune anti-IL2 response is evidenced by the detection or quantification of B cells producing anti-IL-2 AutoAbs or anti-IL-2 antibodies claim 17 , wherein the AutoAbs are neutralizing anti-IL-2 AutoAbs.20. The in vitro method according to claim 16 , wherein the autoimmune disease is selected from the group consisting of type 1 diabetes (T1D) claim 16 , systemic lupus erythematosus (SLE) claim 16 , rheumatoid arthritis (RA) claim 16 , Sjögren's syndrome (SJO) and autoimmune polymyositis (JO1).21. The in vitro method according to claim 16 , wherein the method is a method for determining whether a patient has claim 16 , or is at risk of having or developing claim 16 , an autoimmune disease.22. The in vitro method according to claim 16 , wherein the method is a method ...

ANTI-IL-2 ANTIBODIES AND COMPOSITIONS AND USES THEREOF

The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Rα and IL-2Rβ. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2. 16-. (canceled)7. An isolated antibody or antigen-binding portion thereof that specifically binds human IL-2 , said antibody comprising: (b) a HCDR1 comprising SEQ ID NO: 82, 83, or 84; a HCDR2 comprising SEQ ID NO: 85, or 86; a HCDR3 comprising SEQ ID NO: 87; a LCDR1 comprising SEQ ID NO: 88; a LCDR2 comprising SEQ ID NO: 89; and a LCDR3 comprising SEQ ID NO: 90;', '(c) a HCDR1 comprising SEQ ID NO: 91, 92, or 93; a HCDR2 comprising SEQ ID NO: 94, or 95; a HCDR3 comprising SEQ ID NO: 96; a LCDR1 comprising SEQ ID NO: 97; a LCDR2 comprising SEQ ID NO: 98; and a LCDR3 comprising SEQ ID NO: 99;', '(d) a HCDR1 comprising SEQ ID NO: 100, 101, or 102; a HCDR2 comprising SEQ ID NO: 103, or 104; a HCDR3 comprising SEQ ID NO: 105; a LCDR1 comprising SEQ ID NO: 106; a LCDR2 comprising SEQ ID NO: 107; and a LCDR3 comprising SEQ ID NO: 108;', '(e) a HCDR1 comprising SEQ ID NO: 109, 110, or 111; a HCDR2 comprising SEQ ID NO: 112, or 113; a HCDR3 comprising SEQ ID NO: 114; a LCDR1 comprising SEQ ID NO: 115; a LCDR2 comprising SEQ ID NO: 116; and a LCDR3 comprising SEQ ID NO: 117;', '(f) a HCDR1 comprising SEQ ID NO: 118, 119, or 120; a HCDR2 comprising SEQ ID NO: 121, or 122; a HCDR3 comprising SEQ ID NO: 123; a LCDR1 comprising SEQ ID NO: 124; a LCDR2 comprising SEQ ID NO: 125; and a LCDR3 comprising SEQ ID NO: 126;', '(g) a HCDR1 comprising SEQ ID NO: 127, 128, or 129; a HCDR2 comprising SEQ ID NO: 130, or 131 ...

METHOD FOR DIAGNOSING AND TREATING ATTENTION DEFICIT HYPERACTIVITY DISORDER

The invention provides methods and compositions for treating attention-deficit/hyperactivity disorder (ADHD) in an individual. The methods provided herein entail administering a composition comprising an isolated Mycobacterium or antigenic fragments derived therefrom. Also provided herein are methods for assessing alleviation of symptoms and/or alteration of immune system functioning following administration of a composition comprising an isolated Mycobacterium or antigenic fragments derived therefrom. 1. A method of treating attention-deficit/hyperactivity disorder (ADHD) and the symptoms associated with such a disorder in a subject , comprising administering a therapeutically effective amount of a composition comprising an isolated Mycobacterium to the subject , wherein the subject suffers from or is suspected of suffering from attention-deficit/hyperactivity disorder (ADHD).2. The method of claim 1 , further comprising diagnosing the subject with ADHD prior to the administration of the therapeutically effective amount of the composition comprising an isolated Mycobacterium.3. The method of claim 2 , wherein the diagnosing comprises testing of the subject for an allergic disorder or conducting an assessment of immunologic traits associated with ADHD claim 2 , an assessment of behaviors associated with ADHD or any combination thereof.45.-. (canceled)6. The method of claim 3 , wherein the immunologic traits are alterations in chemokine and/or cytokine production claim 3 , wherein the alterations are an increase in production of one or more chemokines or cytokines claim 3 , a decrease in production in one or more chemokines or cytokines or any combination thereof.7. The method of claim 3 , wherein the immunologic traits associated with ADHD are occurrence of allergic disorders claim 3 , atopy claim 3 , hypersensitivity to allergens or any combination thereof.8. (canceled)9. The method of claim 2 , wherein the diagnosing comprises: determining expression levels of at ...

Targeted Immunotolerance

Methods and compounds for conferring site-specific or local immune privilege. 169-. (canceled)70. A method of increasing T regulatory cell proliferation in a subject , the method comprising administering to the subject a pharmaceutical composition comprising a polypeptide comprising an antibody that binds to MAdCAM on the cell surface and an IL-2 mutein polypeptide (IL-2 mutein) , wherein the IL-2 mutein comprises the amino acid sequence of SEQ ID NO: 6 comprising one or more mutations of E15Q , H16N , Q22E , D84N , E95Q , Q126E , N29S , Y31S , Y31H , K35R , T37A , K48E , N71R , L53I , L56I , L80I , L118I , V69A , Q74P , N88D , N88R , C125A or C125S.71. The method of claim 70 , wherein the IL-2 mutein is fused or linked to a Fc peptide.72. The method of claim 71 , wherein the Fc peptide comprises a mutation at one or more of positions of L234 claim 71 , L235 and G237 according to the EU numbering system or L247 claim 71 , L248 claim 71 , and G250 according to the Kabat numbering system.73. The method of claim 70 , wherein the polypeptide comprises a first chain and a second chain that form the polypeptide claim 70 , whereinthe first chain comprises:VH-Hc-Linker-C1, wherein VH is a variable heavy domain of the antibody that binds to MAdCAM on the cell surface with a VL domain of the second chain; Hc is a heavy chain of antibody comprising CH1-CH2-CH3 domain, the Linker is a glycine/serine linker, and C1 is the IL-2 mutein fused to a Fc protein, wherein the Fc protein is fused or linked at the N-terminus or the C-terminus of the IL-2 mutein; andthe second chain comprises:VL-Lc, wherein VL is a variable light chain domain of the antibody that binds to MAdCAM on the cell surface with the VH domain of the first chain, and the Lc domain is a kappa light chain constant domain.74. The method of claim 70 , wherein the anti-MAdCAM antibody is a non-blocking anti-MAdCAM antibody.75. The method of claim 70 , wherein the anti-MAdCAM antibody is a blocking anti-MAdCAM antibody.76 ...

Antibodies That Bind Interleukin-2 and Uses Thereof

The present disclosure relates, in general, to human antibodies against human interleukin 2 (IL-2) and methods of use of such antibodies for modulating IL-2 activity and use in the treatment of conditions such as cancer, autoimmune disease, or infection. 1. A human or humanized antibody that binds human interleukin-2 (IL-2) with an affinity Kof 1×10M or less and inhibits binding of IL-2 with an IL-2 receptor alpha (IL-2 Rα) subunit ,wherein the antibody inhibits IL-2 signaling through IL-2 Rα h and through IL-2 Rβγ, andwherein the antibody inhibits IL-2 signaling through IL-2 Rα h to a greater extent than through IL-2 Rβγ.2. The antibody of wherein the antibody does not completely block binding of human IL-2 to cells expressing human or mouse IL-2 RR or IL-2 Rβγ complex.3. The antibody of claim 1 , wherein the antibody binds at a site allosteric to binding of IL-2 to IL-2 Rα claim 1 , IL-2 Rβγ or IL-2 Rαβγ.4. The antibody of claim 1 , wherein the antibody is a negative modulator antibody claim 1 , optionally wherein the antibody is capable of weakening the binding affinity between IL-2 with IL-2 receptor α (IL-2 Rα) by at least about 2-fold claim 1 , optionally up to 1000-fold.5. The antibody of wherein IL-2 complexed to the antibody binds to CHO cells expressing IL-2 Rβ and γc with an EC50 of 5 nM or less or wherein IL-2 complexed to the antibody binds to CHO cells expressing IL-2 Rβ (but not γc) with an EC50 of 100 nM or less.6. The antibody of wherein the antibody binds to human IL-2 and one or more of mouse claim 1 , rat or rabbit IL-2.7. The antibody of claim 1 , wherein the antibody inhibits IL-2 stimulation of STAT5 activation in cells expressing IL-2 Rα claim 1 , IL-2 Rβ claim 1 , and γc to a greater extent than cells expressing IL-2 Rβ and γc claim 1 , but not IL-2 Rα.8. The antibody of claim 1 , wherein the antibody inhibits IL-2 stimulation of STAT5 activation in cells that express IL-2 Rα claim 1 , IL-2 Rβ claim 1 , and γc by 200-fold or greater.9. The ...

METHODS FOR IN VIVO EXPANSION OF CD8+ T CELLS AND PREVENTION OR TREATMENT OF GVHD

Disclosed herein are methods of preventing and treating acute GVHD and chronic GVHD after hematopoietic cell transplantation (HCT), as well as methods of in vivo augmenting expansion of donor CD8 T cells in the lymphoid tissues in vivo after HCT and methods of augmenting recipient tissue expression of programmed death-ligand 1 (PD-L1, or B7H1) after HCT. The methods entail administering one or more doses of an effective amount of a therapeutic agent to a recipient simultaneously, immediately before, or immediately after HCT to temporarily deplete CD4 T cells or to reduce serum IL-2. Some examples include an anti-CD4 antibody or an anti-CD4-meditope-immunotoxin, an anti-IL-2 antibody, an agent blocking IL-2R, and/or a PD-L1-Ig. One or more additional therapeutic agents such as IFN- can be administered. 1. A method for preventing or treating graft-versus-host disease (GVHD) while preserving graft versus leukemia/lymphoma (GVL) effects in a subject receiving hematopoietic cell transplantation (HCT) , comprising administering one or more doses of a therapeutically effective amount of a therapeutic agent to the subject to temporarily deplete CD4 T cells in vivo or to temporarily reduce serum IL-2 in the subject , wherein the therapeutic agent is administered to the subject simultaneously with HCT , immediately before HCT , or immediately after HCT.2. The method of claim 1 , wherein the therapeutic agent includes an anti-CD4 antibody claim 1 , an anti-CD4-meditope-immunotoxin claim 1 , an anti-IL-2 antibody claim 1 , an agent blocking IL-2R claim 1 , and a PD-L1-Ig.3. The method of claim 2 , wherein the anti-CD4 antibody is a monoclonal antibody or a humanized antibody.4. The method of claim 2 , wherein the anti-IL-2 antibody is a monoclonal antibody or a humanized antibody.5. The method of claim 1 , further comprising administering one or more doses of IFN- to the subject.6. The method of claim 1 , wherein a first dose of the therapeutic agent is administered to the ...

Anti-il-2 antibodies and compositions and uses thereof

The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Rα and IL-2Rβ. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2.

ANTI-IL-2 ANTIBODIES AND COMPOSITIONS AND USES THEREOF

The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Rα and IL-2Rβ. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2. 1. An isolated antibody or an antigen-binding portion thereof that specifically binds human IL-2 (hIL-2) , wherein the antibody binds helices A and C and the B-C loop of hIL-2.2. An isolated antibody or an antigen-binding portion thereof that specifically binds human IL-2 (hIL-2) , wherein the antibody reduces the binding affinity of hIL-2 to IL-2Rα by 1 to 199 fold.3. The antibody or antigen-binding portion of claim 2 , wherein the antibody reduces the binding affinity of hIL-2 to IL-2Rα by 10 fold.4. An isolated antibody or an antigen-binding portion thereof that specifically binds human IL-2 (hIL-2) claim 2 , wherein the antibody:{'sup': '+', '(a) reduces hIL-2 binding to IL-2Rα and IL-2Rβ, and inhibits an activity in CD8 T cells to a higher degree than in regulatory T (Treg) cells;'}{'sup': '+', '(b) reduces hIL-2 binding to IL-2Rα and IL-2Rβ, and inhibits STAT5 phosphorylation in CD8T cells to a higher degree than in regulatory T (Treg) cells;'}{'sup': +', '+, '(c) reduces hIL-2 binding to IL-2Rα and IL-2Rβ, and increases the ratio of regulatory T (Treg) cells to CD8or CD4 T cells or to NK cells as measured in a peripheral blood mononuclear cell (PBMC) culture or reconstitution assay; or'}(d) reduces hIL-2 binding to IL-2Rα and IL-2Rβ, and increases expression of one or more of FOXP3, CD25, and Icos in regulatory T (Treg) cells.5. The isolated antibody or antigen-binding portion of claim 1 , ...

Anti-SIRPa Antibodies and Methods of Use Thereof

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, antibodies, antibody fragments, etc., that specifically bind a SIRPA polypeptide, e.g., a mammalian SIRPA or human SIRPA, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof. 1. A method of treating cancer in a subject in need thereof , the method comprising administering to the subject a therapeutically effective amount of an isolated antibody that binds to human SIRPA , wherein the antibody comprises a heavy chain variable region and a light chain variable region , wherein the heavy chain variable region comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO:20; an HVR-H2 comprising the amino acid sequence of SEQ ID NO:21; an HVR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 22 , 23 , and 24; and the light chain variable region comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO:9; an HVR-L2 comprising the amino acid sequence of SEQ ID NO:10; and an HVR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , and 19.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the heavy chain variable region comprises one claim 1 , two claim 1 , three or four frame work regions selected from VFR1 comprising the amino acid sequence of SEQ ID NO:25 claim 1 , VFR2 comprising the amino acid sequence of SEQ ID NO:26 claim 1 , VFR3 comprising the amino acid sequence of SEQ ID NO:27 claim 1 , and VFR4 comprising the amino acid sequence of SEQ ID NO:28; and wherein the light chain variable region comprises one claim 1 , two claim 1 , three or four frame work regions selected from VFR1 comprising the amino acid sequence of SEQ ID NO:29 claim 1 , VFR2 comprising the amino acid sequence of SEQ ID NO:30 claim 1 , VL FR3 comprising the amino acid sequence of SEQ ID NO:31 claim 1 , and VFR4 comprising the amino acid sequence of SEQ ID ...

ANTI-HUMAN INTERLEUKIN-2 ANTIBODIES AND USES THEREOF

Provided is an antibody that binds to human interleukin-2 (hIL-2), and more particularly to an anti-hIL-2 antibody that binds specifically to a particular epitope of hIL-2, thereby inhibiting the binding of the hIL-2 to CD25. 1. An anti-hIL-2 antibody or antigen-binding fragment thereof , which binds specifically to human interleukin-2 (hIL-2) , and inhibits the binding of the hIL-2 to CD25.2. The anti-hIL-2 antibody or antigen-binding fragment thereof of claim 1 , wherein the anti-hIL-2 antibody or antigen-binding fragment thereof comprises:a heavy-chain variable region comprising a heavy-chain CDR1 comprising the amino acid sequence of SEQ ID NO: 11, a heavy-chain CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and a heavy-chain CDR3 comprising the amino acid sequence of SEQ ID NO: 13; anda light-chain variable region comprising a light-chain CDR1 comprising the amino acid sequence of SEQ ID NO: 14, a light-chain CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and a light-chain CDR3 comprising the amino acid sequence of SEQ ID NO: 16.3. The anti-hIL-2 antibody of claim 2 , wherein the antibody is a chimeric or humanized antibody.4. The anti-hIL-2 antibody or antigen-binding fragment thereof of claim 2 , wherein the anti-hIL-2 antibody or antigen-binding fragment thereof comprises:a heavy-chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 23, 28, 32, and 34; anda light-chain variable region comprising the amino acid sequence selected from the group consisting of SEQ ID NOS: 4, 24, 26, and 30.5. The anti-hIL-2 antibody or antigen-binding fragment thereof of claim 4 , wherein the anti-hIL-2 antibody or antigen-binding fragment thereof comprises:a heavy-chain variable region of SEQ ID NO: 3 and a light-chain variable region of SEQ ID NO: 4;a heavy-chain variable region of SEQ ID NO: 23 and a light-chain variable region of SEQ ID NO: 24;a heavy-chain variable region of SEQ ID NO: 28 and a ...

PEPTIDES FOR USE IN TREATMENT AND DIAGNOSIS OF TYPE 1 DIABETES

Provided herein are compositions and methods for treating autoimmune diabetes such as type 1 diabetes (T1D), diagnosing autoimmune diabetes such as T1D, assessing treatment efficacy, and selecting subjects for treatment, e.g., using a peptide or epitope disclosed. 1. A composition , comprising at least one peptide , the at least one peptide comprising at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1) , PKTRREAEVGQ (SEQ ID NO: 2) , RREAEDLQGSL (SEQ ID NO: 3) , RREAEDLEGSL (SEQ ID NO: 4) , DLQVGQVELGGGP (SEQ ID NO: 5) , DLQVGEVELGGGP (SEQ ID NO: 6) , CGSHLVEALYLVC (SEQ ID NO: 7) , MNILLEYVVKS (SEQ ID NO: 8) , NMFTYEIAPVFVLLEYV (SEQ ID NO: 9) , NVCFWYIPPSLRTLEDN (SEQ ID NO: 10) , FNQLSTGLDMVGLAADW (SEQ ID NO: 11) , GRTGTYILIDMVLNRMA (SEQ ID NO: 12) , PKAARPPVTPVLLEKKS (SEQ ID NO: 13) , or at least one T cell epitope contained within the at least one amino acid sequence.2. The composition of claim 1 , comprising at least two peptides claim 1 , whereina first peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence; anda second peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), ...

ANTIBODIES THAT BIND INTERLEUKIN-2 AND USES THEREOF

The present disclosure relates, in general, to human antibodies against human interleukin 2 (IL-2) and methods of use of such antibodies for modulating IL-2 activity and use in the treatment of conditions such as cancer, autoimmune disease, or infection. 1. A human or humanized antibody that binds human interleukin-2 (IL-2) with an affinity Kof 1×10° M or less and inhibits binding of IL-2 with an IL-2 receptor alpha (IL-2 Rα) subunit ,wherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ and through IL-2 Rβγ, andwherein the antibody inhibits IL-2 signaling through IL-2 Rαβγ to a greater extent than through IL-2 Rβγ.2. The antibody of wherein the antibody does not completely block binding of human IL-2 to cells expressing human or mouse IL-2 Rβ or IL-2 Rβγ complex.3. The antibody of any one of the preceding claims claim 1 , wherein the antibody binds at a site allosteric to binding of IL-2 to IL-2 Rα claim 1 , IL-2 Rβγ or IL-2 Rαβγ.4. The antibody of any one of the preceding claims claim 1 , wherein the antibody is a negative modulator antibody claim 1 , optionally wherein the antibody is capable of weakening the binding affinity between IL-2 with IL-2 receptor α (IL-2 Rα) by at least about 2-fold claim 1 , optionally up to 1000-fold.5. The antibody of any one of the preceding claims wherein IL-2 complexed to the antibody binds to CHO cells expressing IL-2 Rβ and γc with an EC50 of 5 nM or less or wherein IL-2 complexed to the antibody binds to CHO cells expressing IL-2 Rβ (but not γc) with an EC50 of 100 nM or less.6. The antibody of any one of the preceding claims wherein the antibody binds to human IL-2 and one or more of mouse claim 1 , rat or rabbit IL-2.7. The antibody of any one of the preceding claims claim 1 , wherein the antibody inhibits IL-2 stimulation of STAT5 activation in cells expressing IL-2 Rα claim 1 , IL-2 Rβ claim 1 , and γc to a greater extent than cells expressing IL-2 Rβ and γc claim 1 , but not IL-2 Rα.8. The antibody of any one of ...

Methods and devices for the production and delivery of beneficial factors from stem cells

Provided herein are methods and devices related to inducing a population of self-renewing or senescent stem cells, to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Also provided are compositions and methods for inducing senescence, useful for inducing senescence in a population of stem cells, in order to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Methods and devices to control and customize the production of the beneficial factors for the requirements of a disease or disorder being treated are described. Also provided are factor production units for the production of the beneficial factors, and devices for the delivery of the beneficial factors to an individual in need.

CANCER-TARGETED IL-12 IMMUNOTHERAPY

The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and/or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and/or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases. 1. A method of inducing and/or stimulating an immune response against a cancer disease in a patient suffering from said cancer disease comprising administering a therapeutically effective amount of a monoclonal antibody or a biologically active portion thereof , directed to human DNA-histone H1 complex exposed in tumor necrosis , and fused via its C-terminus to IL12 , wherein said induction or stimulation of the immune response initiates(i) senescence of cancer cells, and/or(ii) remission of cancer cells or cancer tissue to cells or tissue of origin.2. The method of claim 1 , wherein the method further comprises administering an immune modulating and/or immune complementary agent for inducing and/or stimulating the immune response against the cancer disease in the patient suffering from said cancer disease.3. The method of claim 2 , wherein the immune modulating and/or immune complementary agent is a cytokine selected from the interleukin family.4. The method of claim 3 , wherein the cytokine is IL-2 claim 3 , IL-7 claim 3 , or a derivative thereof.5. The method of claim 4 , wherein said IL-2 or IL-7 is used in naked form claim 4 , in covalently bound form claim 4 , or in complex form.6. The method of claim 5 , wherein said IL-2 or IL-7 is covalently fused to an immunoglobulin heavy chain or portion ...

IMMUNE-STIMULATING MONOCLONAL ANTIBODIES AGAINST HUMAN INTERLEUKIN-2

The invention relates to a human Interleukin-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (K)≦7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (K)≦1×10sand/or the antibody displays no measurable cross-reactivity to murine IL-2. 1. A human interleukin-2 (hIL-2) specific monoclonal antibody (mAb) , or antigen binding fragment thereof , wherein binding of said antibody to hIL-2 inhibits binding of hIL-2 to CD25 , and the antibody is characterized by any one of the parameters:a. the variable chain of the mAb comprises an amino acid sequence having an identity of ≧85%, ≧90%, ≧95%, or ≧99% compared to SEQ ID NO 005 or SEQ ID NO 006;{'sub': 'D', 'b. the binding to hIL-2 is characterized by a dissociation constant (K)≦7.5 nmol/L, ≦5 nmol/L, ≦3 nmol/L, ≦2 nmol/L or ≦1.5 nmol/L;'}{'sub': 'off', 'sup': −4', '−1', '−5', '−1', '−5', '−1', '−5', '−1', '−5', '−1', '−5', '−1, 'claim-text': 'and/or', 'c. the binding to hIL-2 is characterized by an off-rate (K)≦1×10s, ≦8×10s, ≦6×10s, ≦4×10s, ≦3×10sor ≦2.1×10s;'}d. the antibody displays no measurable cross-reactivity to murine IL-2.2. The human interleukin-2 (hIL-2) specific monoclonal antibody claim 1 , or antigen binding fragment thereof claim 1 , according to claim 1 , characterized in that it comprises at least one VH and/or one VL sequence having an identity of ≧80% claim 1 , ≧85% claim 1 , ≧90% claim 1 , ≧92% claim 1 , ≧93% claim 1 , ≧94% claim 1 , ≧95% claim 1 , ≧96% claim 1 , ≧97% or ≧98% compared to SEQ ID NOs 019 or 20.3. The human interleukin-2 (hIL-2) specific monoclonal antibody claim 1 , or antigen binding fragment thereof claim 1 , according to claim 1 , characterized in that it ...

IL2RBETA/COMMON GAMMA CHAIN ANTIBODIES

Anti-CD122 and/or γc antibodies and fragments thereof are disclosed. Also disclosed are compositions comprising such antibodies and fragments, and uses and methods using the same. 2. The antibody or antigen binding fragment according to claim 1 , wherein the antigen-binding fragment which binds to CD122 comprises a light chain variable region sequence and a heavy chain variable region sequence claim 1 , wherein:the light chain variable region sequence has at least 70% sequence identity to the light chain variable region sequence of SEQ ID NO:1, andthe heavy chain variable region sequence has at least 70% sequence identity to the heavy chain variable region sequence of SEQ ID NO:35.3. The antibody or antigen binding fragment according to claim 1 , wherein the antigen-binding fragment which binds to common γ chain comprises a light chain variable region sequence and a heavy chain variable region sequence claim 1 , wherein the light chain variable region sequence has at least 70% sequence identity to the light chain variable region sequence of SEQ ID NO:67.4. The antibody or antigen binding fragment according to claim 1 , wherein: the light chain variable region sequence has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:1, and', 'the heavy chain variable region sequence has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:35; and, '(a) the antigen-binding fragment which binds to CD122 comprises a light chain variable region sequence and a heavy chain variable region sequence, wherein(b) the antigen-binding fragment which binds to common γ chain comprises a light chain variable region sequence and a heavy chain variable region sequence, wherein the light chain variable region sequence has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:67.5. The antibody or antigen binding fragment according to claim 1 , which binds to the IL-2Rβ/common γ chain ...

IMMUNE-STIMULATING MONOCLONAL ANTIBODIES AGAINST HUMAN INTERLEUKIN-2

The invention relates to a human lnterieuldn-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hlL-2 inhibits binding of hlL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (K)≤7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (K)≤1×10sand/or the antibody displays no measurable cross-reactivity to murine IL-2. 119-. (canceled)20. A fusion protein comprising:a) a VH domain fragment, wherein said VH domain fragment comprises amino acid sequences of SEQ ID NOs: 007, 008 and 009;b) a VL domain fragment, wherein said VL domain fragment comprises amino acid sequences SEQ ID NOs: 010, 011, and 012; andc) a human interleukin 2 (hIL-2) polypeptide comprising an amino acid sequence having at least 80% sequence identify to SEQ ID NO:001 or SEQ ID NO:002, wherein said hIL-2 polypeptide has hIL-2 activity.21. The fusion protein of claim 20 , wherein said VH domain fragment is fused to the hIL-2 polypeptide to produce a single polypeptide chain.22. The fusion protein of claim 21 , wherein the VH domain fragment is fused to the hIL-2 polypeptide by an amino acid linker claim 21 , wherein said amino acid linker is 1 to 50 amino acids.23. The fusion protein of claim 20 , wherein said VH domain fragment comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 019.24. The fusion protein of claim 20 , wherein said VH domain fragment comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 005.25. The fusion protein of claim 20 , wherein said fusion protein comprises an amino acid sequence having at least 70% sequence identity to SEQ ID NO: 023.26. The fusion protein of claim 20 , wherein said VL domain fragment is fused to the hIL-2 polypeptide to produce a single polypeptide ...

IMMUNE-STIMULATING HUMANIZED MONOCLONAL ANTIBODIES AGAINST HUMAN INTERLEUKIN-2, AND FUSION PROTEINS THEREOF

The present invention relates to antibodies binding to human interleukin-2 (hIL-2). The invention more specifically relates to humanized antibodies specifically binding a particular epitope of hIL-2 and, when bound to this epitope, displaying a unique capability of inhibiting binding of hIL-2 to CD25. 131-. (canceled)32. An antibody/IL-2 fusion protein comprising:1) a first polypeptide comprising a VH domain, wherein said VH domain comprises the amino acid sequences of SEQ ID NOs: 119, 120, and 121;2) a second polypeptide comprising a VL domain, wherein said VL domain comprises the amino acid sequences SEQ ID NOs: 122, 123, and 21; and3) a third polypeptide comprising an amino acid sequence encoding a human interleukin-2 protein (hIL-2),wherein said third polypeptide is inserted into at least one of said VH domain or said VL domain, andwherein said antibody/IL-2 fusion protein has hIL-2 activity.33. The antibody/IL-2 fusion protein of claim 32 , wherein:(a) said VL domain comprises: (1) a LCDR1 selected from the group consisting of SEQ ID NO: 19, SEQ ID NO: 31, SEQ ID NO: 69, SEQ ID NO: 72, SEQ ID NO: 86 and SEQ ID NO: 90; (2) LCDR2 selected from the group consisting of SEQ ID NO: 20 and SEQ ID NO: 32; and (3) a LCDR3 selected from SEQ ID NO: 21 and(b) said VH domain comprises: (a) a HCDR1 selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 4 and SEQ ID NO: 13; (b) a HCDR2 selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 12; and(c) a HCDR3 selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 36, SEQ ID NO: 39, SEQ ID NO: 42, and SEQ ID NO: 45.34. The antibody/IL-2 fusion protein of claim 32 , wherein said antibody/IL-2 fusion protein comprises:(a) the LCDR1, LCDR2 and LCDR3 are SEQ ID NO: 19, 20 and 21, respectively and the HCDR1, HCDR2 and HCDR3 are SEQ ID NO: 4, 2 and 3, respectively; or(b) the LCDR1, LCDR2 and LCDR3 are SEQ ID NO: 31, 32 and 21, respectively and the HCDR1, HCDR2 and HCDR3 are SEQ ID NO: 4, 2 and 3, ...

METHOD OF TREATING A PATHOLOGICAL SYNDROME

A method of treating disorder or condition that relates to intracellular signal transmission of a neurotransmitter, comprising administration of an homeopathically potentized form of antibodies to an antigen, which antigen is a molecule capable of effecting the intracellular signal transmission of a neuroreceptor, in particular dopamine or serotonin. 128-. (canceled)29. A method of treating a disorder or condition that relates to intracellular signal transmission of dopamine in a patient , said method comprising administering to said patient in need thereof a homeopathically potentized form of an antibody to an antigen , which antigen is a molecule capable of effecting said intracellular signal transmission of dopamine.30. The method of claim 29 , wherein said antigen is an endogenous biomolecule.31. The method of claim 30 , wherein said endogenous biomolecule is dopamine.32. The method of claim 29 , wherein said disorder or condition is schizophrenia.33. The method of claim 29 , wherein said disorder or condition is tremors and gait disorders.34. The method of claim 29 , wherein said disorder or condition is chronic gastritis.35. The method of claim 29 , wherein said disorder or condition is night phobias.36. The method of claim 29 , wherein said disorder or condition is Parkinson's disease.37. A method of treating a disorder or condition that relates to intracellular signal transmission of serotonin in a patient claim 29 , said method comprising administering to said patient in need thereof a homeopathically potentized form of an antibody to an antigen claim 29 , which antigen is a molecule capable of effecting said intracellular signal transmission of serotonin.38. The method of claim 37 , wherein said antigen is an endogenous biomolecule.39. The method of claim 38 , wherein said endogenous biomolecule is serotonin.40. The method of claim 37 , wherein said disorder or condition is depression.41. The method of claim 37 , wherein said disorder or condition is ...

MULTISPECIFIC ANTIBODY MOLECULES COMPRISING LAMBDA AND KAPPA LIGHT CHAINS

Multispecific, e.g., bispecific, antibody molecules that include a kappa light chain polypeptide and one lambda light chain polypeptide, and methods of making and using the multispecific antibody molecules, are disclosed. 1. A multispecific antibody molecule comprising: a) a first heavy chain polypeptide (HCP1) comprising: a first heavy chain variable region sequence (HCVRS) sufficient that, when paired with i)b) allows the first antigen-binding domain to bind to the first antigen; and', 'b) a lambda light chain polypeptide (LLCP) comprising: a lambda light chain variable region sequence (LLCVRS) sufficient that, when paired with i)a) allows the first antigen-binding domain to bind to the first antigen; and, 'i) a first antigen-binding domain that binds to a first antigen, wherein the first antigen-binding domain comprises a) a second heavy chain polypeptide (HCP2) comprising: a second heavy chain variable region sequence (HCVRS) sufficient that, when paired with ii)b) allows the second antigen-binding domain to bind to the second antigen; and', 'b) a kappa light chain polypeptide (KLCP) comprising: a kappa light chain variable region sequence (KLCVRS) sufficient that, when paired with ii)a) allows the second antigen-binding domain to bind to the second antigen, wherein:, 'ii) a second antigen-binding domain that binds to a second antigen, wherein the second antigen-binding domain comprises1) the first HCVRS has at least 75, 80, 85, 90, 95, 98, or 100% sequence identity with a first heavy chain germline sequence selected from column 3 of Table 7, column 2 of Table 8b, or column 2 of Table 5b;2) the LLCVRS has at least 75, 80, 85, 90, 95, 98, or 100% sequence identity with a lambda light chain germline sequence selected from column 4 of Table 7, column 3 of Table 8b; or column 3 of Table 5b;3) the second HCVRS has at least 75, 80, 85, 90, 95, 98, or 100% sequence identity with a second heavy chain germline sequence selected from column 3 of Table 6, column 5 of Table ...

Il2rbeta/common gamma chain antibodies

Anti-CD122 and/or γc antibodies and fragments thereof are disclosed. Also disclosed are compositions comprising such antibodies and fragments, and uses and methods using the same.

PNEUMOCOCCAL INHIBITORY FACTOR COMPOSITIONS AND METHODS OF USE THEREOF

An isolated or recombinant aminopeptidase N (pepN) polypeptide having inflammatory cytokine production and cytolysis inhibiting activity is provided. A method of inhibiting inflammatory cytokine production and cytolysis in a subject in need thereof is also provided, comprising administering to the subject an inflammatory cytokine production and cytolysis inhibiting amount of the isolated or recombinant pneumococcal pepN polypeptide. A method of treating a disease, disorder, or condition characterized by or associated with undesirable inflammatory cytokine production and cytolysis in a subject in need thereof is also provided, comprising administering to the subject a therapeutically effective amount of an isolated or recombinant pepN polypeptide. A method of treating pneumococcal infection in a subject in need thereof is also provided comprising administering to the subject a therapeutically effective amount of an anti-pepN polypeptide inhibitory agent. 1. An isolated or recombinant aminopeptidase N (pepN) polypeptide , wherein the isolated or recombinant pepN polypeptide comprises the amino acid sequence of SEQ ID NO:1 or a functional variant thereof , wherein the functional variant thereof has inflammatory cytokine production and cytolysis inhibiting activity and comprises an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO:1.2. The isolated or recombinant pepN polypeptide of claim 1 , wherein the isolated or recombinant pepN polypeptide is fused to a heterologous polypeptide.3. The isolated or recombinant pepN polypeptide of claim 2 , wherein the heterologous polypeptide is an epitope tag.4. The isolated or recombinant pepN polypeptide of claim 1 , wherein the functional variant is a functional fragment of an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 1.5. A composition comprising the isolated or recombinant pepN polypeptide of in a pharmaceutically acceptable carrier.6. A method of ...

INHIBITION OF KIDNEY DISEASE RELAPSE BY TARGETED CYTOKINE DEPLETION

Described herein are methods for inhibiting the acute relapse or worsening of glomerular disease in response to viral infections associated with the common cold or flu comprising administration of anti-cytokine antibodies, anti-receptor antibodies, soluble receptors, or blocking agents to a subject in need thereof. Also described are methods for depleting a subjects systemic levels of one or more of cytokines IL-2, IL-6, IL-10, INF-γ, or TNFα, or inhibiting the receptors IL-4R or ICAM-1 comprising contacting the cytokines or receptors with one or more anti-cytokine antibodies, anti-receptor antibodies, soluble receptors, or blocking agents. 1. A method for inhibiting acute relapse or worsening of a glomerular disease initiated by a viral infection , the method comprising administration to a subject in need thereof of one or more anti-cytokine antibodies , anti-receptor antibodies , soluble receptors , or blocking agents , wherein the subject is in complete or partial remission of the glomerular disease prior to the viral infection and the viral infection comprises a virus that induce a common cold or flu.2. The method of claim 1 , wherein the one or more anti-cytokine antibodies claim 1 , anti-receptor antibodies claim 1 , soluble receptors claim 1 , or blocking agents comprise one or more of anti-IL-2 claim 1 , anti-IL-6 claim 1 , anti-IL-10 claim 1 , anti-INF-γ claim 1 , anti-TNFα claim 1 , soluble TNF receptors claim 1 , anti-IL-4R claim 1 , anti-IL-4Ra claim 1 , anti-IL-6 receptor claim 1 , anti-ICAM-1 claim 1 , or combinations thereof.3. The method of claim 1 , wherein the one or more anti-cytokine antibodies claim 1 , anti-receptor antibodies claim 1 , soluble receptors claim 1 , or blocking agents comprise one or more of anti-IL-4R claim 1 , anti-IL-6 claim 1 , anti-IL-6 receptor claim 1 , anti-TNFα claim 1 , soluble TNF receptors claim 1 , or combinations thereof.4. The method of claim 1 , wherein the one or more anti-cytokine antibodies claim 1 , anti- ...

Humanized cc chemokine receptor 4 (ccr4) antibodies and methods of use thereof

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.

Inhibitor which is deactivatable by a reagent produced by a target cell

The invention relates to molecules inhibiting biologically active compounds and further comprising moieties specifically cleavable by a reagent produced by a target cell. More specifically, the invention relates to inhibitors that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent. Inhibitors comprise at least one moiety that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent and at least one moiety that can be cleaved specifically by a reagent produced by target cells. The cleavage deactivates the inhibitor. Following cleavage, the active agent is liberated into the local environment. Administration of the inhibitor alone or together with the active agent suppress the compound's activity until it reaches the proximity of a target cell. This targeted specific release enables the agent concentration in a site to reach levels that have desired therapeutic effects without systemic toxicity. The invention also relates to production and uses of the inhibitors in diagnosis and treatment of a disease. 1. An inhibitor which is deactivatable by a reagent produced by a target cell comprising:(a) a first moiety that binds, inhibits, suppresses, neutralizes, or decreases activity of a biologically active agent wherein said first moiety is operably linked to;(b) a second moiety specifically cleavable by a reagent produced by a target cell, wherein said first and second moieties are not attached in nature and wherein specific cleavage of said second moiety causes reduction of binding, inhibiting, suppressing, or neutralizing activity of said inhibitor.2. The inhibitor of claim 1 , wherein said first moiety is selected from the group consisting of a peptide claim 1 , a cyclic peptide claim 1 , a polypetide claim 1 , a peptidomimetic claim 1 , a protein claim 1 , a fusion protein claim 1 , a hybrid molecule or a dimer claim 1 , multimer claim 1 , or a conjugate of the above.3. The inhibitor of claim 1 , ...

Method for Enrichment and Expansion of Virus Antigen-Specific T Cells

The present invention relates to a method for inducing and proliferating target virus antigen-specific dual activated T cells, and can produce target virus antigen-specific dual activated T cells by treating monocytes, which are isolated from peripheral blood, with a cytokine and a virus antigen peptide mixture and culturing the same. 1. A method for inducing and proliferating dual activated T cells , comprising:treating peripheral blood mononuclear cells with IFN-γ and a virus antigen peptide mixture upon the culture of the peripheral blood mononuclear cells; andtreating the peripheral blood mononuclear cells with IL-2.2. The method of claim 1 , wherein the treating of the peripheral blood mononuclear cells with the IFN-γ and the virus antigen peptide mixture is carried out on day 0 of the culture.3. The method of claim 1 , wherein the treating of the peripheral blood mononuclear cells with the IL-2 is carried out on day 4 of the culture.4. The method of claim 1 , wherein the peripheral blood mononuclear cells are obtained from a normal person or a patient.5. The method of claim 1 , wherein the IFN-γ is used at a concentration of 500 U/mL to 1 claim 1 ,000 U/mL.6. The method of claim 1 , wherein the IL-2 is used at a concentration of 200 U/mL to 1 claim 1 ,000 U/mL.7. The method of claim 1 , wherein the induction and proliferation of the dual activated T cells is carried out for a total of 20 days or more.8. The method of claim 7 , wherein the induction and proliferation of the dual activated T cells is carried out for a total of 21 days.9. The method of claim 1 , wherein the virus antigen comprises antigens selected from the group consisting of a cytomegalovirus (CMV) claim 1 , Epstein-Barr virus (EBV) claim 1 , an adenovirus (ADV) claim 1 , and BK virus (BKV).10. (canceled)11. (canceled)12. A method for treating a virus-mediated disease claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the dual activated T cells obtained as ...

Hypotaurine, GABA, Beta-Alanine, and Choline for Control of Waste Byproduct Accumulation in Mammalian Cell Culture Process

The present invention pertains to a cell culture medium comprising hypotaurine, GABA, and/or beta-alanine or the combination of choline and hypotaurine, GABA, and/or beta-alanine as media supplements which is shown to control viability, growth, and waste byproduct accumulation. The present invention further pertains to a method of producing a polypeptide of interest in a large scale cell culture containing hypotaurine, GABA, and/or beta-alanine or the combination of choline and hypotaurine, GABA, and/or beta-alanine. 1. A method of producing a polypeptide of interest in a large-scale cell culture , comprising culturing mammalian cells expressing the polypeptide of interest in a cell culture medium under conditions that support expression of the polypeptide of interest , wherein said cell culture medium comprises hypotaurine , Gamma-Aminobutyric Acid (GABA) , and/or beta-alanine.2. A method of producing a polypeptide of interest in a large-scale cell culture , comprising supplementing the culture with a feed medium comprising a sufficient amount of hypotaurine , Gamma-Aminobutyric Acid (GABA) , or beta-alanine to achieve a hypotaurine , GABA , or beta-alanine concentration , respectively , in the culture between about 0.1 mM and 500 mM , wherein the culture comprises cells expressing the polypeptide and a medium , and the cells are maintained under conditions that allow for expression of the polypeptide.3. A method of producing a polypeptide of interest in a large-scale cell culture , comprising:a) providing cells capable of expressing the polypeptide and a hypotaurine-, Gamma-Aminobutyric Acid (GABA)-, or beta-alanine-containing cell culture medium;b) supplementing the culture with a feed medium comprising a sufficient amount of hypotaurine, GABA, or beta-alanine to achieve a hypotaurine, GABA, or beta-alanine concentration, respectively, of between about 0.1 mM to 500 mM; andc) culturing the cells of b) to allow for expression of the polypeptide.4. The method of ...

Method of Treating Psoriasis in Pediatric Subjects with Anti-IL12/IL23 Antibody

Anti-IL-12/IL-23p40 antibodies, such as ustekinumab, are used in methods and compositions for safe and effective treatment of psoriasis, particularly moderate to severe chronic plaque psoriasis, in pediatric patients. The methods and compositions address a clear unmet medical need in this patient population. 1. A method of treating psoriasis in a pediatric patient in need thereof , comprising administering to the pediatric patient a pharmaceutical composition comprising a safe and effective amount of an anti-IL-12/IL-23p40 antibody , wherein the antibody comprises a heavy chain variable region and a light chain variable region , the heavy chain variable region comprises: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1 , a CDRH2 amino acid sequence of SEQ ID NO:2 , and a CDRH3 amino acid sequence of SEQ ID NO:3 , and the light chain variable region comprises: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4 , a CDRL2 amino acid sequence of SEQ ID NO:5 , and a CDRL3 amino acid sequence of SEQ ID NO:6 , and wherein the pediatric patient is at least 6 years old and is less than 12 years old and is a responder to treatment with the anti-IL-12/IL-23p40 antibody by being identified as having a Physician's Global Assessment (PGA) score of 0 or 1 after treatment and/or identified as having at least 75% , 90% or 100% reduction in Psoriasis Area and Severity Index Score (PASI).2. The method of claim 1 , wherein the antibody is administered subcutaneously to the pediatric patient.3. The method of claim 2 , wherein the pediatric patient has a body weight less than 60 kg at the time of the administration claim 2 , and the anti-IL-12/IL-23p40 antibody is administered subcutaneously to the patient at the safe and effective amount of about 0.5 mg/kg to 1.0 mg/kg claim 2 , preferably 0.75 mg/kg claim 2 , body weight of the pediatric patient claim 2 , per administration.4. The method of claim 2 ...

MODULATING THE EFFECTS OF GAMMA-C-CYTOKINE SIGNALING FOR THE TREATMENT OF ALOPECIA AND ALOPECIA ASSOCIATED DISORDERS

The γc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as alopecia and alopecia associated disorders. Compositions, methods, and kits to modulate signaling by at least one γc-cytokine family member for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one alopecia related disorder are described. 149-. (canceled)50. A composition , comprising:a therapeutic compound in an amount sufficient to modulate signaling by at least one γc-cytokine family member, thereby inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one alopecia related disorder; anda pharmaceutically acceptable carrier;wherein the therapeutic compound is a γc cytokine antagonist peptide;wherein the γc cytokine antagonist peptide shares at least 90% identity with a peptide of SEQ ID NO: 1 (BNZ-γ).51. The composition of claim 50 , wherein the at least one alopecia related disorder is selected from the group consisting of alopecia claim 50 , pemphigus claim 50 , pemphigoid claim 50 , psoriasis claim 50 , vitiligo claim 50 , graft-versus-host disease claim 50 , and immune-mediated hair loss.52. The composition of claim 50 , wherein the γc cytokine antagonist peptide comprises 19 to 50 amino acids.53. The composition of claim 50 , wherein the γc cytokine antagonist peptide further comprises a conjugate at the N-termini claim 50 , C-termini claim 50 , side residues claim 50 , or a combination thereof.54. The compositions of claim 53 , wherein the conjugate comprises one or more additional moieties selected from the group consisting of bovine serum albumin (BSA) claim 53 , albumin claim 53 , Keyhole Limpet Hemocyanin (KLH) claim 53 , Fc region of IgG claim 53 , a biological protein that functions as scaffold claim 53 , an antibody against a cell ...

Anti-Sirpa Antibodies and Methods of Use Thereof

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, antibodies, antibody fragments, etc., that specifically bind a SIRPA polypeptide, e.g., a mammalian SIRPA or human SIRPA, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof. 1. An isolated antibody that binds to human SIRPA , wherein the antibody comprises a heavy chain variable region and a light chain variable region , wherein the heavy chain variable region comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO:20; an HVR-H2 comprising the amino acid sequence of SEQ ID NO:21; an HVR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 22 , 23 , and 24; and the light chain variable region comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO:9; an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10; and an HVR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , and 19.2. (canceled)3. (canceled)4. The antibody of claim 1 , wherein the heavy chain variable region comprises one claim 1 , two claim 1 , three or four frame work regions selected from VH FR1 comprising the amino acid sequence of SEQ ID NO:25 claim 1 , VH FR2 comprising the amino acid sequence of SEQ ID NO:26 claim 1 , VH FR3 comprising the amino acid sequence of SEQ ID NO:27 claim 1 , and VH FR4 comprising the amino acid sequence of SEQ ID NO:28; and/or wherein the light chain variable region comprises one claim 1 , two claim 1 , three or four frame work regions selected from VL FR1 comprising the amino acid sequence of SEQ ID NO:29 claim 1 , VL FR2 comprising the amino acid sequence of SEQ ID NO:30 claim 1 , VFR3 comprising the amino acid sequence of SEQ ID NO:31 claim 1 , and VL FR4 comprising the amino acid sequence of SEQ ID NO:32.5. The antibody of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence at least 90% or at ...

Engineered heterodimeric protein domains

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

Immunocytokine combination therapy

This invention relates ιο methods and compositions, in a combination therapy, for treatment of neoplastic disease, including tenors and cancer, wherein an immunocytokine arid a small molecule drug conjugate which comprises a moiety capable of binding to a tumor-associated target,

METHODS OF HIGH-THROUGHPUT IDENTIFICATION OF T CELL EPITOPES BY CAPTURING CYTOKINES ON THE SURFACE OF ANTIGEN-PRESENTING CELLS

The present invention relates to a methods for high throughput screening of epitopes that are involved in T cell activation.

METHODS AND DEVICES FOR THE PRODUCTION AND DELIVERY OF BENEFICIAL FACTORS FROM STEM CELLS

Provided herein are methods and devices related to inducing a population of self-renewing or senescent stem cells, to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Also provided are compositions and methods for inducing senescence, useful for inducing senescence in a population of stem cells, in order to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Methods and devices to control and customize the production of the beneficial factors for the requirements of a disease or disorder being treated are described. Also provided are factor production units for the production of the beneficial factors, and devices for the delivery of the beneficial factors to an individual in need. 174.-. (canceled)75. A method of expanding regulatory T-cell (Tregs) , the method comprising:growing a population of human adipose derived stem cells (hADSCs);adding an inducing agent comprising IL-2 to the population of hADSCs for about 24 hours to induce the production of the one or more secreted factors by the population of hADSCs;collecting the one more secreted factors about 72 hours post-induction; andcontacting peripheral blood mononuclear cells (PBMCs) with the one or more secreted factors to induce expansion of the Tregs.76. The method of claim 75 , wherein the population of hADSCs comprise self-renewing (SR) cells and senescent (SEN) cells.77. The method of claim 75 , wherein the population of hADSCs comprise at least 50% SR cells.78. The method of claim 75 , wherein the population of hADSCs comprise at least 50% SEN cells.79. The method of claim 75 , wherein the secreted factors are produced in a factor production unit.80. A method for modulating immune cells claim 75 , the method comprising:providing a population of human adipose derived stem cells (hADSCs);adding an inducing agent comprising IL-2 to the population of hADSCs for about 24 hours to induce the production of one or ...

METHODS AND MATERIALS FOR TARGETED EXPANSION OF IMMUNE EFFECTOR CELLS

This document relates to methods and materials for targeted expansion of immune effector (Eff) T cells. For example, a composition containing one or more amino acid chains (e.g., one or more single-chain antibody/cytokine fusion proteins (immunocytokines)) that can bind to a heterodimeric receptor including an interleukin-2 receptor-β (IL-2Rβ) polypeptide and a common gamma chain (γ) polypeptide (e.g., an IL-2Rβ/γpolypeptide complex) can be administered to a mammal to stimulate Effs within the mammal to activate an immune response in that mammal. In some cases, methods and materials that can be used to treat a mammal having a condition that can benefit from activating an immune response (e.g., a cancer and/or an infectious disease) are provided. For example, a composition containing one or more single-chain immunocytokines that can bind to an IL-2Rβ/γpolypeptide complex can be administered to a mammal having a cancer and/or an infectious disease to treat the mammal. 2. (canceled)3. (canceled)4. The single-chain immunocytokine of claim 1 , wherein said immunoglobulin heavy chain comprises a γ heavy chain constant domain.5. (canceled)6. (canceled)7. The single-chain immunocytokine of claim 1 , wherein said immunoglobulin heavy chain comprises a signal sequence.8. The single-chain immunocytokine of claim 7 , wherein said signal sequence comprises an amino acid sequence set forth in SEQ ID NO:6.9. The single-chain immunocytokine of claim 1 , wherein said immunoglobulin heavy chain comprises an amino acid sequence set forth in SEQ ID NO:1 or SEQ ID NO:26.1013-. (canceled)14. The single-chain immunocytokine of claim 1 , wherein said immunoglobulin light chain comprises a κ light chain constant domain.15. (canceled)16. (canceled)1712. The single-chain immunocytokine of claim claim 1 , wherein said immunoglobulin light chain comprises a signal sequence.18. The single-chain immunocytokine of claim 17 , wherein said signal sequence comprises an amino acid sequence set forth ...

IMPLANTABLE SCAFFOLDS AND USES THEREOF FOR IMMUNOTHERAPY AND OTHER USES

An implantable or injectable scaffold comprising immunostimulatory compounds and a suppressor of regulatory T cell induction is provided for use in immunotherapy treatments, including the treatment of cancers and other tumors, in particular solid tumors including inoperable tumors, as well as for other applications of immune enhancement and/or suppression. 1. A porous scaffold comprising:(a) at least one compound that regulates T cell immune response; and(b) at least one compound that regulates induction of regulatory T cells (Tregs).2. The porous scaffold of claim 1 , wherein the at least one compound that regulates T cell immune response comprises a T cell immunostimulatory compound or a T cell immunosuppression compound.3. The porous scaffold of claim 2 , wherein the at least one compound that regulates T cell immune response comprises a T cell immunostimulatory compound and the at least one compound that regulates induction of Tregs comprises a compound that suppresses induction of Tregs.4. The porous scaffold of claim 2 , wherein the T cell immunostimulatory compound comprises a T cell activator claim 2 , a T cell attractant or a T cell adhesion compound.5. The porous scaffold of claim 2 , wherein the T cell immunostimulatory compound comprises a cytokine claim 2 , a therapeutic or diagnostic protein claim 2 , a growth factor claim 2 , a chemokine claim 2 , a therapeutic or diagnostic antibody or fragment thereof claim 2 , an antigen-binding protein claim 2 , a Fc fusion protein claim 2 , an anticoagulant claim 2 , an enzyme claim 2 , a hormone claim 2 , a thrombolytic claim 2 , a peptide claim 2 , an oligonucleotide claim 2 , a nucleic acid claim 2 , a chemokine ligand claim 2 , or an anti-cluster of differentiation (anti-CD) antibody or fragment thereof.6. The porous scaffold of claim 5 , wherein the cytokine comprises an interleukin.7. The porous scaffold of claim 1 , wherein the T cell immunostimulatory compound comprising interleukin-2 (IL-2) claim 1 , ...

A fusion monoclonal antibody comprising IGF-R1 antibody and IL-2, and pharmaceutical composition comprising the same

본 발명은 암세포 표면 항원인 IGF-1R에 특이적으로 결합할 수 있는 항 IGF-1R 단일클론 항체와 면역세포의 활성을 증가시키는 IL-2가 결합된 융합 단일클론 항체, 상기 융합 단일클론 항체의 제조방법 및 상기 융합 단일클론 항체를 유효성분으로 포함하는 암치료용 조성물에 관한 것이다. 본 발명의 융한 단일클론 항체는 IL-2에 의해 암세포 주변의 면역세포가 강하게 활성화 되어 대조 항암항체 또는 보고된 항IGF-1R 항체보다 증가된 항체의존성 세포독성을 나타낼 수 있으므로, 보다 효과적인 항암치료에 널리 활용될 수 있을 것이다. The present invention relates to a fusion monoclonal antibody comprising an anti-IGF-1R monoclonal antibody capable of specifically binding to a cancer cell surface antigen, IGF-1R, and IL-2 increasing the activity of immune cells, And a composition for treating cancer comprising the fusion monoclonal antibody as an active ingredient. Since the fusion monoclonal antibody of the present invention strongly activates the immune cells around the cancer cells by IL-2, it can exhibit an increased antibody-dependent cytotoxicity compared with the reference anti-cancer antibody or the reported anti-IGF-1R antibody, It can be widely used.

Immunostimulatory humanized monoclonal antibodies against human interleukin-2 and fusion proteins thereof

本发明涉及与人白介素‑2(hIL‑2)结合的抗体。本发明更具体涉及特异性结合hIL‑2的特定表位的人源化抗体，该抗体在结合该表位时展示出抑制hIL‑2与CD25结合的独特能力。

Multispecific antibody molecules comprising lambda and kappa light chains

Multispecific, e.g., bispecific, antibody molecules that include a kappa light chain polypeptide and one lambda light chain polypeptide, and methods of making and using the multispecific antibody molecules, are disclosed.

Interleukin-2 agents and uses thereof

IL-2 agents that comprise IL-2 variants are disclosed as well as methods, compositions, and uses thereof. The IL-2 agents described herein can be used to treat and/or prevent various disorders and conditions.

Immune activating fc domain binding molecules

The present invention generally relates to novel immune activating Fc domain binding molecules for activation of immune cells and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such 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.

Engineered heterodimeric protein domains

Humanized CC chemokine receptor 4 (CCR4) antibodies and methods of use thereof

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4- IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce

Immunocytokines with progressive activation mechanism

Interleukin-2 muteins for the expansion of t-regulatory cells.

Se proporcionan aquí muteínas de IL-2, moléculas de fusión de muteína de IL-2 Fc, anticuerpos anti-IL-2 y complejos que comprenden un anticuerpo anti-IL-2 unido a una citoquina de IL-2 que expanden y activan preferiblemente células T reguladoras y son susceptibles de producción a gran escala. También se proporcionan aquí moléculas Fc de IgG1 humanas variantes que carecen o con función efectora altamente reducida y alta estabilidad a pesar de que carecen de glicosilación en N297. También se proporcionan aquí péptidos enlazadores que están glicosilados cuando se expresan en células de mamífero. También se proporcionan en la presente invención métodos para fabricar y usar las composiciones de la presente invención.

Compositions comprising TL1A-Ig fusion protein for the regulation of T regulatory cells, and methods for their use

Compositions comprising TL1A-Ig fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin).

Compositions comprising TLIA-Ig fusion protein for the regulation of T regulatory cells, and methods for their use

Compositions comprising TL1A-Ig fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin).

A cd25-biased anti-il-2 antibody

The invention provides a human IL-2 (hlL-2)-specific monoclonal antibody, wherein a complex of hlL-2 and the monoclonal induces IL-2 signalling preferentially via CD25 and the trimeric IL-2R. The invention further provides a pharmaceutical composition comprising hlL-2 and said hlL-2-mAb for use treating inflammatory disease.

Dual ox40 agonist/il-2 cancer therapy methods

OX40 is a potent immune stimulating target. Provided herein is a method of treating cancer, which includes administering to a subject in need of treatment an OX40 agonist and a common gamma chain (yc) cytokine or an active fragment, variant, analog, or derivative thereof In certain aspects the common gamma chain (yc) cytokine is interleukin-2 (IL-2) or an active fragment, variant, analog, or derivative thereof. Combined treatment with an agonist anti-OX40 mAb and IL-2 synergized to augment tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8 + T cells.

Multi-specificity antibody molecule comprising lambda light chain and κ light chain

公开了包含κ轻链多肽和一个λ轻链多肽的多特异性抗体分子例如双特异性抗体分子，以及制备和使用所述多特异性抗体分子的方法。

Interleukin-2 agonists and uses thereof

IL-2 변이체를 포함하는 IL-2 작용제뿐만 아니라, 이의 방법, 조성물 및 용도도 개시되어 있다. 본원에 기재된 IL-2 작용제는 다양한 장애들 및 병태들을 치료하고/하거나 예방하는 데 사용될 수 있다.

Novel use of IL-1beta compounds

This disclosure relates to a novel use of IL-1β-ligand/IL-1 receptor disrupting compounds (herein referred to as "IL-1 beta Compounds"); such as small molecular compounds disrupting IL-1β ligand - IL-1 receptor interaction, IL-1β antibodies or IL-1 receptor antibodies, e.g. IL-1β binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1β binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1β ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Methods for the production of proteins with a desired function

La présente invention se rapporte à un procédé de production de protéines présentant une fonction souhaitée, qui consiste à (a) prévoir une population de cellules produisant des anticorps et soupçonnées de contenir au moins une cellule pouvant produire un anticorps présentant une fonction souhaitée; b) mettre en suspension la population de cellules produisant des anticorps dans un milieu dans lequel est incorporé un système indicateur, ce système pouvant aussi indiquer la présence et l'emplacement d'une cellule qui produit des anticorps présentant la fonction souhaitée; c) identifier une cellule produisant un anticorps ayant la fonction souhaitée; d) isoler du milieu la cellule identifiée produisant l'anticorps; e) déterminer la séquence d'acides aminés de la région variable ou d'une partie de celle-ci conférant la fonction souhaitée à l'anticorps produit par la cellule isolée; et f) synthétiser une protéine présentant la fonction voulue, cette protéine contenant la séquence d'acides aminés de la région variable ou de la partie de celle-ci qui confère cette fonction souhaitée. The present invention relates to a method of producing proteins having a desired function, which comprises (a) providing a population of antibody-producing cells suspected of containing at least one cell capable of producing an antibody having a desired function; b) suspending the population of antibody-producing cells in a medium having incorporated therein an indicator system, which system may also indicate the presence and location of a cell which produces antibodies exhibiting the desired function; c) identifying a cell producing an antibody having the desired function; d) isolating the identified antibody-producing cell from the medium; e) determining the amino acid sequence of the variable region or part thereof conferring the desired function on the antibody produced by the isolated cell; and f) synthesizing a protein having the desired function, which ...

Anti-il-2 antibodies and compositions and uses thereof

The present invention provides antibodies, or antigen-binding fragments thereof, which specifically bind to IL-2. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppresion.

Anti-il-2 antibodies and compositions and uses thereof

The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2R.alpha. and IL-2R.beta.. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. These antibodies may be used in compositions and therapeutic methods for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2.

Formulations of human anti-TSLP antibodies and methods of using the same

Provided herein are compositions comprising greater than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer comprising greater than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer. Methods for treating an inflammatory disease in a subject are further provided.

Anti-il-2 antibody, and antigen-binding fragment thereof and medical use thereof

Provided are an anti-IL-2 antibody, and an antigen-binding fragment thereof and the medical use thereof. Further provided are a complex (including a fusion protein) of the anti-IL-2 antibody, the antigen-binding fragment thereof and IL-2, and the use of the complex as a drug for treating autoimmune diseases and inflammatory diseases.

Anti-sirpa antibodies and methods of use thereof

The present disclosure is generally directed to compositions that include antibodies, e.g. , monoclonal, antibodies, antibody fragments, etc. , that specifically bind a SIRPA polypeptide, e.g. , a mammalian SIRPA or human SIRPA, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Formulations of human anti-tslp antibodies and methods of using the same

Provided herein are compositions comprising greater than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer comprising greater than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer. Methods for treating an inflammatory disease in a subject are further provided.

Anti-il-2 antibodies and compositions and uses thereof

The present invention provides antibodies, or antigen-binding portions thereof,　which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Ra and IL-2Rβ. The invention further provides a method of obtaining such antibodies and　nucleic acids encoding the same. The invention further relates to compositions and　therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2.

The adjoint method and kit of therapy based on IL-2 and the therapy based on mescenchymal stem cell

本文描述的是用于基于IL‑2的疗法和用于基于间充质干细胞的疗法的伴随方法和试剂盒。

Antibodies Against Programmed death-ligand 1 and Uses Thereof

본 발명은 PD-L1(Programmed death-ligand 1)에 대한 항체 또는 이의 항원 결합 단편, 이를 코딩하는 핵산, 상기 핵산을 포함하는 벡터, 상기 벡터로 형질전환된 세포, 상기 항체 또는 그의 항원 결합 단편의 제조방법, 이를 포함하는 암의 예방 또는 치료용 조성물 및 병용 투여용 조성물에 관한 것이다. The present invention relates to an antibody or antigen-binding fragment thereof against PD-L1 (Programmed death-ligand 1), a nucleic acid encoding the same, a vector containing the nucleic acid, a cell transformed with the vector, and the antibody or antigen-binding fragment thereof. It relates to a preparation method, a composition for preventing or treating cancer, and a composition for co-administration comprising the same.

Use of IL-1beta compounds

This invention relates to methods employing IL-1β-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1β ligand-IL-1 receptor interaction, IL-1β antibodies or IL-1 receptor antibodies, e.g. IL-1β binding molecules as described herein, e.g. antibodies disclosed herein, e.g. IL-1β binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1β ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Methods of using IL-1β compounds to treat familial mediterranean fever (FMF)

This invention relates to methods employing IL-1β-ligand/IL-1 receptor disrupting compounds such as IL-1β antibodies or IL-1 receptor antibodies, in the treatment and/or prevention of Familial Mediterranean Fever (FMF), in mammals, particularly humans.

Dual binding moiety

Interleukin-2 muteins for the expansion of t-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Interleukin-2 muteins for the expansion of T-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Interleukin-2 muteins for the expansion of t-regulatory cells

Provided herein are IL-2 muteins, IL-2 mutein Fc-fusion molecules, anti-IL-2 antibodies, and complexes comprising an anti IL-2 antibody bound to an IL-2 cytokine that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also provided herein are linker peptides that are glycosylated when expressed in mammalian cells. Also provided herein are methods of making and using the compositions of the present invention.

Method for expanding primate b cells selectively in immunocompromised mice and producing large numbers of antigen-specific b lymphocytes for the production of primate monoclonal antibodies

The present invention relates to a method for reconstituting immunocompromised mice with primate cells, consisting of the following steps: (a) preparation of an immunocompromised mouse by administration of an antibody against the beta chain of the mouse interleukin 2 (IL-2) receptor, more particularly the monoclonal mouse TM-β1 monoclonal antibody and/or gamma irradiation, (b) intraspleen injection of primate cells into the spleen of the pre-treated immunocompromised mouse of step (a), where these primate cells preferably originate from a primate donor and where this primate donor may have been immunised with a well-defined antigen. This method was found to be highly suitable for expanding primate B lymphocytes in an animal model in a rapid, as yet unequalled manner. Other embodiments of this invention relate to immunocompromised mice obtained by the aforesaid method and also the use thereof as animal models, primate B cell culture produced and primate monoclonal antibodies derived therefrom.

Immunocytokines with progressive activation mechanism

The present invention relates to a combination comprising at least an immunocytokine comprising at least a primary binding protein or peptide and a cytokine, fused or conjugated to one another, and a secondary binding molecule capable of binding to at least a section of at least one cytokine comprised in the immunocytokine.

Antibodies that bind interleukin-2 and uses thereof

【課題】ヒトインターロイキン２（ＩＬ－２）に対するヒト抗体、ならびにＩＬ－２活性の調節のためのかかる抗体の使用方法、およびがん・自己免疫疾患・感染症などの状態の治療における使用方法を提供する。【解決手段】１×１０－１０Ｍ以下の親和性ＫＤでヒトインターロイキン２（ＩＬ－２）に結合し、ＩＬ－２受容体アルファ（ＩＬ－２ Ｒα）サブユニットとのＩＬ－２の結合を阻害する、ヒト抗体又はヒト化抗体であって、ＩＬ－２ Ｒαβγを介したＩＬ－２シグナル伝達及びＩＬ－２ Ｒβγを介したＩＬ－２シグナル伝達を阻害し、ＩＬ－２ Ｒαβγを介したＩＬ－２シグナル伝達をＩＬ－２ Ｒβγを介するよりも大きい程度で阻害する、ヒト抗体又はヒト化抗体を提供する。【選択図】なし

Stable liquid pharmaceutical formulation of IgG antibodies

This invention is directed to a stable liquid pharmaceutical formulation comprising a high concentration, e.g. 50 mg/ml or more, of antibody in about 20-60 mM succinate buffer or 30-70 mM histidine buffer, having pH from about pH 5.5 to about pH 6.5, about 0.01-0.1% polysorbate, and a tonicity modifier that contributes to the isotonicity of the formulation. This liquid formulation is stable at refrigerated temperature (2-8° C.) for at least 1 year, and preferably 2 years. This liquid formulation is suitable for subcutaneous injection. The preferred antibodies include Daclizumab, a humanized anti-IL-2 receptor monoclonal antibody; HAIL-12, a humanized anti-IL-12 monoclonal antibody; HuEP5C7, a humanized anti-L selectin monoclonal antibody; and Flintozumab, a humanized anti-gamma interferon monoclonal antibody.

Protease-activated polypeptides

The present invention generally relates to novel isolated polypeptides and immunoconjugates and their uses. The polypeptides and immunoconjugates comprise at least one protease recognitions sequence, which is a substrate for matriptase.

Immune cell therapy for nerve injury

자연살해세포, 면역세포, 또는 그의 활성을 증가시키는 물질을 포함하는 신경손상 치료용 조성물에 관한 것으로, 일 양상에 따른 자연살해세포, 면역세포 또는 그의 활성을 증가시키는 물질에 의하면, 자연살해세포가 손상된 신경부위로 침투하여 손상된 신경세포를 직접 제거함으로써 신경 손상 또는 비정상적 신경에 의한 신경계 질환의 근본적 치료에 유용하게 사용될 수 있는 효과가 있다. It relates to a composition for treating nerve damage comprising a natural killer cell, an immune cell, or a substance that increases its activity, and according to an aspect, the natural killer cell, the immune cell, or a substance that increases the activity thereof, the natural killer cell is By directly removing the damaged nerve cells by penetrating into the damaged nerve area, there is an effect that can be usefully used for the fundamental treatment of nerve damage or neurological diseases caused by abnormal nerves.

Anti-IL-2 antibodies and compositions and uses thereof

본 발명은 IL-2에 특이적으로 결합하여, IL-2Rα 및 IL-2Rβ에 대한 IL-2 결합의 친화도를 감소시키는, 항체, 또는 이의 항원-결합 부분을 제공한다. 본 발명은 상기 항체 및 이를 암호화하는 핵산을 수득하는 방법을 추가로 제공한다. 본 발명은 상기 항체 및 IL-2를 포함하는 복합체를 투여하는 단계를 포함하지만, 이것으로 제한되지 않는, 자가면역 질환, 장애 또는 병태를 치료 및/또는 예방하고, 면역억제를 위한 이러한 항체의 조성물 및 이러한 항체를 사용하는 치료 방법을 추가로 제공한다.

Novel use of il-1beta compounds

Anti-human interleukin-2 antibody and its uses

Novel use of il-1beta compounds

This invention relates to a novel use of IL-1.beta.-ligand/IL-1 receptor disrupting compounds (herein referred to as "IL-1beta Compounds"); such as small molecular compounds disrupting IL-1.beta. ligand - IL-1 receptor interaction, IL-1.beta. antibodies or IL-1 receptor antibodies, e.g. IL-1.beta. binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1.beta. binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1.beta. ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Novel use of il-1beta compounds

This application relates to a use of IL-lβ;-ligand/IL-l receptor disrupting compounds (herein referred to as 'IL-lbeta Compounds'); such as small molecular compounds disrupting IL-lβ; ligand - IL-I receptor interaction, IL-lβ; antibodies or IL-I receptor antibodies, e.g. IL-lβ; binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-lβ; binding compounds or IL-I receptor binding compounds, and/or RNA compounds decreasing either IL-lβ; ligands or IL-I receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.