阅读说明：本技术 用于炎性病症的抗il-1r3抗体 (anti-IL-1R 3 antibodies for inflammatory disorders ) 是由 S·费舍尔 K·贝克曼 于 2018-05-08 设计创作，主要内容包括：本发明涉及通过表征IL1R3信号传导途径成员如IL-1α、IL-1β、IL-33、IL-36、IL1RA和/或IL1R3及其变体的失控或异常表达,治疗医学病症和/或疾病的方法。更具体地,本发明涉及用于治疗受试者中IL1R3介导的炎性病症和/或疾病的抗IL1R3抗体。这类病症和疾病包括但不限于炎性疾病、免疫性疾病、纤维化疾病、嗜酸粒细胞性疾病、感染、疼痛、中枢神经系统障碍、眼病、遗传性全身性炎性疾病、及全身性和局部炎性疾病以及癌症相关的慢性炎症。(The present invention relates to methods of treating medical conditions and/or diseases by characterizing uncontrolled or abnormal expression of IL1R3 signaling pathway members, such as IL-1 α, IL-1 β, IL-33, IL-36, IL1RA, and/or IL1R3 and variants thereof, more specifically, the invention relates to anti-IL 1R3 antibodies for treating IL1R 3-mediated inflammatory conditions and/or diseases in a subject, such conditions and diseases include, but are not limited to, inflammatory diseases, immunological diseases, fibrotic diseases, eosinophilic diseases, infections, pain, central nervous system disorders, ocular diseases, inherited systemic inflammatory diseases, and systemic and local inflammatory diseases, as well as cancer-associated chronic inflammation.)

1. An anti-IL 1R3 antibody for use in treating an IL1R 3-mediated inflammatory disorder and/or disease in a subject.

2. The anti-IL 1R3 antibody according to claim 1, wherein the inflammatory disorder and/or disease is selected from the group consisting of inflammatory disorders, immunological diseases, fibrotic diseases, eosinophilic diseases, infections, pain, central nervous system disorders, ocular diseases, inherited systemic inflammatory diseases, and systemic and localized inflammatory diseases.

3. The anti-IL 1R3 antibody according to claim 2, wherein the inflammatory disorder is a metabolic rheumatic disease associated with hyperuricemia.

4. The anti-IL 1R3 antibody according to claim 3, wherein the metabolic rheumatic disease is selected from the group of gout, pseudogout, drug-induced gout, and chronic active (refractory) gout.

5. The anti-IL 1R3 antibody of claim 4, wherein the IL1R3 antagonist antibody is administered in combination with a therapeutic agent for treating gout.

6. The anti-IL 1R3 antibody according to claim 2, wherein the inflammatory disorder is cancer-associated chronic inflammation.

7. The anti-IL 1R3 antibody of claim 6, wherein the IL1R3 antagonist antibody is administered in combination with one or more cytotoxic, cytostatic and/or targeted anti-cancer agents.

8. The anti-IL 1R3 antibody according to claim 6 or 7, wherein the subject is characterized by resistance to treatment with one or more cytotoxic, cytostatic, and/or targeted anti-cancer agents.

9. The anti-IL 1R3 antibody according to any preceding claim, wherein the antibody has reduced or absent its effector function.

10. The anti-IL 1R3 antibody according to any preceding claim, wherein the antibody does not induce immune cell depletion.

11. The anti-IL 1R3 antibody according to claim 9 or 10, wherein the antibody does not induce ADCC.

12. The anti-IL 1R3 antibody according to any one of claims 9 to 11, wherein the antibody comprises at least the amino acid substitutions L234A and L235A of the human IgG1Fc region or S228P and L235E of the human IgG4 Fc region or corresponding functional mutations.

13. The anti-IL 1R3 antibody of any one of the preceding claims, wherein the subject is a human subject and the antibody comprises

a) Heavy chain variable region (VH) comprising complementarity determining regions including CDR-H1, CDR-H2 and CDR-H3

Wherein the CDR-H1 region comprises an amino acid sequence selected from the group of SEQ ID NOs 69-85,

wherein the CDR-H2 region comprises an amino acid sequence selected from the group of SEQ ID NOS: 86-102,

and wherein the CDR-H3 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO 103-119;

and

b) a light chain variable region (VL) comprising complementarity determining regions including CDR-L1, CDR-L2 and CDR-L3

Wherein the CDR-L1 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO 120-136,

wherein the CDR-L2 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:137-153, and

wherein the CDR-L3 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:154-170 and SEQ ID NO: 175.

14. The anti-IL 1R3 antibody of any one of the preceding claims, wherein the subject is a human subject and the antibody comprises a heavy chain Variable (VH) region that is at least 90% identical to a VH region selected from the group consisting of the VH regions of SEQ ID NOs 1 to 34 and 173, and a light chain Variable (VL) region; the light chain Variable (VL) region is at least 90% identical to a VL region selected from the group consisting of the VL regions of SEQ ID NOs 35 to 68 and 174.

15. The anti-IL 1R3 antibody according to any one of claims 1 to 12, wherein the subject is a mouse and the antibody comprises

a) Heavy chain variable region (VH) comprising complementarity determining regions including CDR-H1, CDR-H2 and CDR-H3

Wherein the CDR-H1 region comprises the amino acid sequence of SEQ ID NO:178,

wherein the CDR-H2 region comprises the amino acid sequence of SEQ ID NO 179,

and wherein the CDR-H3 region comprises the amino acid sequence of SEQ ID NO 180,

and

b) a light chain variable region (VL) comprising complementarity determining regions including CDR-L1, CDR-L2 and CDR-L3

Wherein the CDR-L1 region comprises the amino acid sequence of SEQ ID NO:181,

wherein the CDR-L2 region comprises the amino acid sequence of SEQ ID NO:182, and

wherein the CDR-L3 region comprises the amino acid sequence of SEQ ID NO: 183.

16. The anti-IL 1R3 antibody of any one of claims 1-12, wherein the subject is a mouse and the antibody comprises a heavy chain Variable (VH) region that is at least 90% identical to the VH region of SEQ ID NO:176 and a light chain Variable (VL) region; the light chain Variable (VL) region is at least 90% identical to the VL region of SEQ ID NO: 177.