Monoclonal antibodies against antithrombin β

Patent metadata

Field	Value
Publication number	US-9908942-B2
Application number	US-201414770222-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

This patent document relates to antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human antithrombin β complexed with heparin and/or heparin-like structure (ATβH). These ATβH binding proteins can block the anti-coagulant activity of ATβ to induce coagulation. Therapeutic uses of these antibodies and binders are described herein as are methods of panning and screening specific antibodies.

First claim

We claim:

1. A monoclonal antibody capable of binding the antithrombin β heparin complex (ATH), wherein the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (AYRMG) of SEQ ID NO: 2, a CDR2 sequence of amino acids 50 to 66 (RIYSSGGRTRYADSVKG) of SEQ ID NO: 2, and a CDR3 sequence of amino acids 97 to 114 (AREKASDLSGSFSEALDY) of SEQ ID NO: 2; and
wherein the light chain of said antibody comprises: a CDR1 sequence of amino acids 24 to 34 (QGDSLRSYY AS) of SEQ ID NO: 1, a CDR2 sequence of amino acids 50 to 56 (GKNNRPS) of SEQ ID NO: 1; and a CDR3 sequence of amino acids 89 to 99 (NSRDSSGNHLV) of SEQ ID NO: 1.

2. A monoclonal antibody capable of binding ATH, wherein the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (KYKMD) of SEQ ID NO: 4, a CDR2 sequence of amino acids 50 to 66 (RIGPSGGKTM YADSVKG) of SEQ ID NO: 4, and a CDR3 sequence of amino acids 97 to 114 (AREKASDLSG TYSEALDY) of SEQ ID NO: 4; and
wherein the light chain of said antibody comprises: a CDR1 sequence of amino acids 26 to 37 (RASQSVSSSYLA) of SEQ ID NO: 3, a CDR2 sequence of amino acids 53 to 59 (GASSRAT) of SEQ ID NO: 3, and a CDR3 sequence of amino acids 92 to 99 (QQYGSSRT) of SEQ ID NO: 3.

3. A monoclonal antibody capable of binding ATH, wherein the heavy chain of said antibody comprises: a CDR1 sequence of amino acids 31 to 35 (KYRMD) of SEQ ID NO: 6, a CDR2 sequence of amino acids 50 to 66 (RIGPSGGKTT YADSVKG) of SEQ ID NO: 6, and a CDR3 sequence of amino acids 97 to 114 (AREKTSDLSG SYSEALDY) of SEQ ID NO: 6; and
wherein the light chain of said antibody comprises: a CDR1 sequence of amino acids 26 to 36 (RASQNINRNLA) of SEQ ID NO: 5, a CDR2 sequence of amino acids 52 to 58 (TASTRAP) of SEQ ID NO: 5, and a CDR3 sequence of amino acids 91 to 99 (QQYASPPRT) of SEQ ID NO: 6.

4. The isolated monoclonal antibody of claim 1 , wherein the antibody is selected from the group consisting of an IgG 1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, an IgE antibody, and an antibody fragment.

5. A pharmaceutical composition comprising a therapeutically effective amount of the monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.

6. The isolated monoclonal antibody of claim 2 , wherein the antibody is selected from the group consisting of an IgG 1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, an IgE antibody, and an antibody fragment.

7. The isolated monoclonal antibody of claim 3 , wherein the antibody is selected from the group consisting of an IgG 1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, an IgE antibody, and an antibody fragment.

Assignees

• Bayer Healthcare Llc
• Bayer Healthcare Llc

Inventors

• Jin Ye
• Murphy John E
• Hermiston Terry
• Myles Timothy
• Dittmer Frank
• Strerath Michael
• Gritzan Uwe

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K16/36 Primary

  against blood coagulation factors · CPC title