IP Library › Granted Patent US 10,501,549
Granted Patent B2
US 10,501,549 · App. 15/450,272 · Granted Dec 10, 2019

Methods of inhibiting pathological angiogenesis with doppel-targeting molecules

Inventors: Youngro Byun (Seoul, KR); In San Kim (Daegu, KR); Ahmed Al-Hilal Taslim (Seoul, KR); Sang-Yoon Kim (Seoul, KR); Ye Ji Jang (Seoul, KR)
Assignees: SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION; UNIVERSITY OF ULSAN; KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY; PHAROSGEN
C07K16/2872A61K47/55A61K47/554A61K47/61A61P35/00C07K16/30C12N15/113C12Q1/68G01N33/57492G01N33/6893A01K2217/075A01K2227/105A61K2039/505C07K2317/70C07K2317/73C07K2317/76C12N2310/11C12N2310/3515G01N2333/705
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Quick Facts
Patent No.
US 10,501,549
App. No.
15/450,272
Granted
Dec 10, 2019
Kind
B2
Abstract

Described herein are doppel-targeting molecules useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as tumors, cancers, atherosclerosis, tuberculosis, asthma, pulmonary arterial hypertension (PAH), neoplasms and neoplasm-related conditions, and for detecting doppel expression in a subject. Related compositions and methods also are described.

Claims (23)

1. An antibody that binds to doppel or a doppel-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, wherein:

(a) the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 15;

(b) the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 36; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18;

(c) the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 20; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 21;

(d) the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 42; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24; or

(e) the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and the light chain variable region comprising a CDRL1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 26; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 27.

2. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof is a monoclonal antibody.

3. A pharmaceutical composition comprising an anti-doppel antibody or doppel-binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier or diluent.

4. The antibody or doppel-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 36; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3comprising the amino acid sequence of SEQ ID NO: 18.

5. The antibody or fragment thereof according to claim 4 , wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO: 56 or a sequence at least 90% identical thereto; and the light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 50 or a sequence at least 90% identical thereto.

6. The doppel-binding antibody fragment according to claim 4 , wherein the doppel-binding antibody fragment binds to the dimeric form of doppel.

7. The antibody or doppel-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 20; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 21.

8. The antibody or fragment thereof according to claim 7 , wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO: 57 or a sequence at least 90% identical thereto; and the light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 51 or a sequence at least 90% identical thereto.

9. The doppel-binding antibody fragment according to claim 7 , wherein the doppel-binding antibody fragment binds to non-glycosylated doppel with greater affinity than glycosylated doppel.

10. The antibody or doppel-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 42; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24.

11. The antibody or fragment thereof according to claim 10 , wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO: 58 or a sequence at least 90% identical thereto; and the light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 52 or a sequence at least 90% identical thereto.

12. The doppel-binding antibody fragment according to claim 10 , wherein the doppel-binding antibody fragment binds to non-glycosylated doppel with greater affinity than glycosylated doppel.

13. The antibody or doppel-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and the light chain variable region comprising a CDRL1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 26; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 27.

14. The antibody or fragment thereof according to claim 13 , wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO: 59 or a sequence at least 90% identical thereto; and the light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 53 or a sequence at least 90% identical thereto.

15. The doppel-binding antibody fragment according to claim 13 , wherein the doppel-binding antibody fragment specifically binds to SEQ ID NO: 12 or SEQ ID NO: 61.

16. The antibody or doppel-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and the light chain variable region comprises a CDRL1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 15.

17. The antibody or doppel-binding fragment thereof according to claim 16 , wherein the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO: 55 or a sequence at least 90% identical thereto; and the light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 49 or a sequence at least 90% identical thereto.

18. The doppel-binding antibody fragment according to claim 16 , wherein the-doppel-binding antibody fragment specifically binds to SEQ ID NO: 11.

Priority Claims (1)
KR 10-2015-0168485 · Nov 30, 2015 · national
Continuity (2)
Continuation In Part 15363103 · Nov 29, 2016
Related Publication 20170260278A1 · Sep 14, 2017