KR-102962228-B1 - Humanized anti-CD73 antibody

Abstract

The present invention provides a humanized 1E9 antibody capable of binding specifically to CD73. The humanized antibody is useful for cancer treatment. A nucleic acid encoding the humanized 1E9 antibody and a method for inhibiting cell proliferation using the humanized antibody provided herein are further provided.

Inventors

• 그리핀 에밀리 피쵸네
• 밀러 리차드 에이
• 프레이 게하르트 요한
• 창 화이 원

Assignees

• 코버스 파마슈티칼스, 인크.
• 바이오아트라, 인코퍼레이티드

Dates

Publication Date

20260507

Application Date

20161209

Priority Date

20151209

Claims (20)

1. A humanized anti-CD73 1E9 antibody comprising a humanized light chain variable region and a humanized heavy chain variable region, wherein the humanized light chain variable region comprises the sequence of SEQ ID NO. 36 or SEQ ID NO. 37 and the humanized heavy chain variable region comprises the sequence of SEQ ID NO. 7.
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12. In claim 1, a humanized anti-CD73 1E9 antibody that is IgG.
13. In claim 1, the humanized anti-CD73 1E9 antibody which is IgG1.
14. In claim 1, the humanized anti-CD73 1E9 antibody which is IgG4.
15. In claim 1, a humanized anti-CD73 1E9 antibody that is a Fab' fragment.
16. In claim 1, the humanized anti-CD73 1E9 antibody, which is a single-strand antibody (scFv).
17. A humanized anti-CD73 1E9 antibody capable of binding to a CD73 antigen with an equilibrium dissociation constant (K D ) of 0.5 to 25 nM, according to claim 1.
18. In claim 1, a humanized anti-CD73 1E9 antibody capable of binding to CD73 antigen at a pH of less than 7.5.
19. In claim 1, a humanized anti-CD73 1E9 antibody capable of binding to CD73 antigen at a pH of 6.0 to 7.0.
20. In claim 1, a humanized anti-CD73 1E9 antibody capable of binding to the CD73 antigen at a pH of 6.3.

Description

Humanized anti-CD73 antibody [Cross-reference to related applications] This application claims priority to U.S. Provisional Application No. 62/265,357 filed December 9, 2015, U.S. Provisional Application No. 62/289,694 filed February 1, 2016, and U.S. Provisional Application No. 62/346,327 filed June 6, 2016, the full text of which is incorporated herein by reference for all purposes. [Reference to attachments of sequence lists, tables, or computer program lists submitted as ASCII text files] A sequence list written in the file 48517-508001WO_ST25.TXT, which is 50,442 bytes and was created on December 9, 2016, on a machine format IBM-PC, MS Windows operating system, is incorporated herein by reference. Glycosyl-phosphatidylinositol-attached CD73 antigens are considered rate-limiting enzymes in the production of extracellular adenosine (Reference: Stagg J, Smyth MJ. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene. 2010;29:5346-58. doi: 10.1038/onc.2010.292). CD73 is known to be expressed at high levels in a homeostatic manner on various types of cancer cells. CD73-generated adenosine is presumed to promote tumor growth and metastasis by suppressing adaptive anti-tumor immune responses. In the art, there is a demand for CD73 cancer therapies based on antibodies that inhibit metastasis by inhibiting the catalytic activity of CD73 and blocking the ability of circulating tumor cells to squirt and aggregate. The present invention addresses these and other requirements in the art. In one embodiment, a humanized 1E9 antibody is provided, comprising a humanized light chain variable region comprising mouse CDR L1, mouse CDR L2, or mouse CDR L3 and a humanized heavy chain variable region comprising mouse CDR H1, mouse CDR H2, or mouse CDR H3. In one embodiment, an antibody (e.g., a humanized 1E9 antibody) is provided. The antibody comprises a light chain (e.g., a humanized light chain) variable region and a heavy chain (e.g., a humanized heavy chain) variable region. The light chain variable region comprises: (i) CDR L1 presented in SEQ ID NO. 1 (e.g., mouse CDR L1), CDR L2 presented in SEQ ID NO. 2 (e.g., mouse CDR L2), CDR L3 presented in SEQ ID NO. 3 (e.g., mouse CDR L3) and (ii) valine at the position corresponding to kabat position 2, methionine at the position corresponding to kabat position 4, aspartic acid or leucine at the position corresponding to kabat position 9, proline or serine at the position corresponding to kabat position 12, lysine or proline at the position corresponding to kabat position 18, alanine at the position corresponding to kabat position 43, proline or serine at the position corresponding to kabat position 60, threonine at the position corresponding to kabat position 74, asparagine or serine at the position corresponding to kabat position 76, asparagine or serine at the position corresponding to kabat position 77, isoleucine or leucine at the position corresponding to kabat position 78, serine or alanine at the position corresponding to kabat position 80, glutamine at the position corresponding to kabat position 100, valine at the position corresponding to kabat position 104, glutamic acid or alanine at the position corresponding to kabat position 1, glutamine at the position corresponding to kabat position 3, and at kabat position 10 Phenylalanine or threonine at the corresponding position, glutamine at the position corresponding to kabat position 11, alanine or leucine at the position corresponding to kabat position 13, threonine at the position corresponding to kabat position 14, valine or proline at the position corresponding to kabat position 15, lysine at the position corresponding to kabat position 16, glutamic acid or aspartic acid at the position corresponding to kabat position 17, threonine at the position corresponding to kabat position 22, lysine at the position corresponding to kabat position 42, arginine at the position corresponding to kabat position 45, isoleucine at the position corresponding to kabat position 58, tyrosine at the position corresponding to kabat position 67, phenylalanine at the position corresponding to kabat position 73, tyrosine at the position corresponding to kabat position 85, or phenylalanine at the position corresponding to kabat position 87. The heavy chain variable region comprises: (i) CDR H1 presented at SEQ ID NO. 4 (e.g., mouse CDR H1), CDR H2 presented at SEQ ID NO. 5 (e.g., mouse CDR H2), CDR H3 presented at SEQ ID NO. 6 (e.g., mouse CDR H3) and (ii) Isoleucine at the position corresponding to kabat position 37, alanine or proline at the position corresponding to kabat position 40, lysine at the position corresponding to kabat position 43, serine at the position corresponding to kabat position 70, isoleucine or threonine at the position corresponding to kabat position 75, tryptophan at the position corresponding to kabat position 82, arginine or lysine at the position corresponding to kabat position 83, alanine at the