Human monoclonal antibodies against interleukin 8 (IL-8)
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-016/24
A61K-039/395
A61K-045/06
C07K-016/42
G01N-033/68
A61K-039/00
출원번호
US-0138490
(2016-04-26)
등록번호
US-10066012
(2018-09-04)
발명자
/ 주소
Teeling, Jessica
Parren, Paul
Baadsgaard, Ole
Hudson, Debra
Petersen, Jørgen
출원인 / 주소
CORMORANT PHARMACEUTICALS AB
대리인 / 주소
Nelson Mullins Riley & Scarborough LLP
인용정보
피인용 횟수 :
0인용 특허 :
53
초록▼
Isolated human monoclonal antibodies which bind to IL-8 (e.g., human IL-8) are disclosed. The human antibodies can be produced in a hybridoma, transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoi
Isolated human monoclonal antibodies which bind to IL-8 (e.g., human IL-8) are disclosed. The human antibodies can be produced in a hybridoma, transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals, hybridomas, and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.
대표청구항▼
1. An isolated recombinant monoclonal antibody which binds to human IL-8 comprising a variable heavy chain amino acid sequence as set forth in SEQ ID NO:12 and a variable light chain amino acid sequence as set forth in SEQ ID NO:8. 2. An isolated recombinant monoclonal antibody which binds to human
1. An isolated recombinant monoclonal antibody which binds to human IL-8 comprising a variable heavy chain amino acid sequence as set forth in SEQ ID NO:12 and a variable light chain amino acid sequence as set forth in SEQ ID NO:8. 2. An isolated recombinant monoclonal antibody which binds to human IL-8, wherein the antibody comprises a human heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:22, 23, and 24, respectively, and a human light chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:16, 17 and 18, respectively. 3. The antibody of claim 2, wherein the antibody is an IgG1 antibody. 4. The antibody of claim 3, wherein the antibody is an IgG1κ or IgG1λ, isotype. 5. The antibody of claim 3, comprising an IgG1 or IgG3 heavy chain. 6. The antibody of claim 2, wherein the antibody has one or more of the following characteristics: (i) inhibits IL-8 binding to its receptors (CXCR1 and CXCR2); (ii) inhibits IL-8 induced proinflanimatory effects; (iii) inhibits IL-8 induced chemotactic activity for neutrophils; (iv) inhibits IL-8 induced calcium flux; (v) inhibits IL-8 induced changes in expression levels of adhesion molecules on neutrophils; (vi) inhibits IL-8 induced increased expression of CD11b (Mac-1) and inhibits IL-8 induced decreased expression of L-selectin on neutrophils; or (vii) does not cross-react with related chemokines selected from the group consisting of human GRO-alpha, human GRO-beta, human IP-10 and human NAP-2. 7. The antibody of claim 2 having a dissociation equilibrium constant (KD) of approximately 10−8 M or less, when determined by surface plasmon resonance (SPR) technology using recombinant human IL-8 as the analyte and the antibody as the ligand. 8. The antibody of claim 2 which is an antibody fragment or a single chain antibody. 9. The antibody of claim 2 which is a binding-domain immunoglobulin fusion protein comprising (i) a variable heavy chain amino acid sequence as set forth in SEQ ID NO:12, fused to a variable light chain amino acid sequence as set forth in SEQ ID NO:8 via a linker peptide, that is fused to an immunoglobulin hinge region polypeptide, (ii) an immunoglobulin heavy chain CH2 constant region fused to the hinge region, and (iii) an immunoglobulin heavy chain CH3 constant region fused to the CH2 constant region. 10. The antibody of claim 2, produced by a hybridoma which includes a B cell obtained from a transgenic non-human animal, in which V-(D)-J gene segment rearrangements have resulted in the formation of a functional human heavy chain transgene and a functional human light chain transgene, fused to an immortalized cell. 11. A bispecific or multispecific molecule comprising the antibody according to claim 2, and a binding specificity for a human effector cell. 12. The molecule of claim 11, wherein the binding specificity for a human effector cell is selected from the group consisting of a binding specificity for a human Fc gamma receptor, a human Fc alpha receptor, and a T cell receptor. 13. A composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier. 14. The composition of claim 13, comprising at least one therapeutic agent. 15. The composition of claim 14, wherein the agent is selected from the group consisting of agents for treating inflammatory or hyperproliferative skin disorders, and anti-inflammatory agents.
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