Anti-platelet membrane glycoprotein IB ALPHA humanized antibody and application thereof

A technology for humanizing antibodies and glycoproteins, which can be used in the field of biomedicine and can solve problems such as evaluation

Active Publication Date: 2021-03-16
CCOA (HANGZHOU) THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, these anti-GPIbα mAbs and their Fab fragments cannot be evaluated for preclinical pharmacology, toxicology and pharmacokinetics in rodents or other small experimental animals

Method used

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  • Anti-platelet membrane glycoprotein IB ALPHA humanized antibody and application thereof
  • Anti-platelet membrane glycoprotein IB ALPHA humanized antibody and application thereof
  • Anti-platelet membrane glycoprotein IB ALPHA humanized antibody and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0104] Example 1 Humanization of murine antibody NIT-B1

[0105] by murine antibodies NIT-A1 and NIT-B1 (described in U.S. Patent Serial No. 8323652 and deposited at the International Depository of Canada on October 7, 2008, respectively, with accession number 071008-01 (clone NIT A1) And 071008-02 (clone NIT B1)) sequencing found that the murine antibody NIT-A1 contains a heavy chain sequence SEQ ID NO: 1 (including CDR1 sequence SEQ ID NO: 3, CDR2 sequence SEQ ID NO: 4 and CDR3 sequence SEQ ID NO:5) and a light chain sequence of SEQ ID NO:11 (including CDR1 sequence of SEQ ID NO:13, CDR2 sequence of SEQ ID NO:14 and CDR3 sequence of SEQ ID NO:15). The murine antibody NIT-B1 contains a heavy chain sequence of SEQ ID NO: 6 (including CDR1 sequence of SEQ ID NO: 8, CDR2 sequence of SEQ ID NO: 9 and CDR3 sequence of SEQ ID NO: 10) and a light chain sequence of SEQ ID NO : 16 (containing CDR1 sequence SEQ ID NO: 18, CDR2 sequence SEQ ID NO: 19 and CDR3 sequence SEQ ID NO: 20). ...

Embodiment 2

[0107] Example 2 Identification of Humanized Anti-GPIbα Antibody

[0108] Using the CDR grafting method (Safdari et al., 2013), four human heavy chain variable regions (VH1 sequence SEQ ID NO: 35, VH2 sequence SEQ ID NO: 42, VH3 sequence SEQ ID NO: 49 and VH4 sequence SEQ ID NO: 56) and four human light chain variable regions (VL1 sequence SEQ ID NO: 63, VL2 sequence SEQ ID NO: 70, VL3 sequence SEQ ID NO: 77 and VL4 sequence SEQ ID NO: 84) were synthesized. The selection of sequences was based on the homology ranking of human CDR region framework sequences annotated in NCBI database.

[0109] Briefly, the variable domain sequences of the parental antibodies were searched against the database of human germline immunoglobulins using NCBI Immunoglobulin Sequence Blast (http: / / www.ncbi.nlm.nih.gov / projects / igblast / ) . For the heavy and light chains, four different human acceptor sequences (ie, human variable domains with high homology to the parental antibody) were selected, res...

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PUM

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Abstract

Multivalent anti-human platelet membrane glycoprotein Ib alpha antibodies can cause severe side effects. The present disclosure provides an Fc moiety-deficient humanized antibody fragment of anti-glycoprotein Ib alpha, so the fragment does not interact with the Fc receptor. The humanized antibody can prevent platelet activation and aggregation, reduce thrombus volume/generation and prevent vascular blockage; and platelet-tumor cell interaction and tumor metastasis can also be reduced. The humanized antibody does not cause platelet activation, does not cause thrombocytopenia at a therapeutic dose, and does not cause bleeding time extension at a therapeutic dose.

Description

[0001] Cross References and Sequence Listing Statements to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 62 / 946,086 filed December 10, 2019 and incorporated in its entirety. The Sequence Listing associated with this application is provided in text format and is hereby incorporated by reference into this specification. The name of the text file containing the sequence listing is PCT_-_Sequence_listing_as_filed. The text file is 81.2Ko, created on December 9, 2020 and filed electronically. technical field [0003] The present invention relates to humanized antibodies that specifically recognize and bind to platelet glycoprotein I(b)α (GPIbα) and protein constructs comprising the same, and their related therapeutic uses. [0004] The invention belongs to the field of biomedicine, and specifically relates to a humanized antibody or its fragment or its chimeric protein with high specificity and high affinity binding to pla...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18C07K19/00A61K39/395A61P7/02A61P9/10A61P9/00A61P31/00A61P35/04
CPCC07K16/18A61P7/02A61P9/10A61P9/00A61P31/00A61P35/04C07K2317/24C07K2317/565C07K2317/92C07K2319/00A61K2039/505C07K16/2896C07K2317/76C07K2317/55C07K2317/33A61P7/00A61P35/00C07K2317/54C07K2317/622C07K2319/31
Inventor 倪合宇
Owner CCOA (HANGZHOU) THERAPEUTICS LTD
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