IP Library › Granted Patent US 12673997
Granted Patent B2
US 12673997 · App. 19/420,662 · Granted Jul 7, 2026

PD-1 binding proteins, VEGF and PD-1 bispecific binding proteins, compositions, and methods of use

Inventors: Byong Ha Kang (Waltham, MA); Hussam Hisham Shaheen (Waltham, MA); Gopalan Raghunathan (Waltham, MA); Ghassan Najib Fayad (Waltham, MA); Mohammad Murshid Alam (Waltham, MA)
Assignee: Paragon Therapeutics, Inc.
C07K16/2818C07K16/22A61K2039/505C07K2317/31C07K2317/73C07K2317/77C07K2317/92C07K2317/94
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12673997
App. No.
19/420,662
Granted
Jul 7, 2026
Kind
B2
Abstract

Bispecific antibodies that bind VEGF and PD-1, pharmaceutical compositions thereof, and methods of use thereof, including methods of inhibiting VEGF and PD-1 biological activities.

Claims (21)

1 . A bispecific binding protein comprising:

(a) a PD-1 binding region comprising an anti-PD-1 immunoglobulin heavy chain variable domain (anti-PD-1 V H ) that comprises, according to Kabat numbering, a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 445, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 446, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 457; and an anti-PD-1 immunoglobulin light chain variable domain (anti-PD-1 V L ) that comprises, according to Kabat numbering, a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 448, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 449, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 450; and

(b) a VEGF binding region comprising an anti-VEGF immunoglobulin heavy chain variable domain (anti-VEGF V H ) that comprises, according to Kabat numbering, a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 433, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 434, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 435; and an anti-VEGF immunoglobulin light chain variable domain (anti-VEGF V L ) that comprises, according to Kabat numbering, a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 436, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 437, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 438.

2 . The bispecific binding protein of claim 1 , wherein the anti-PD-1 V H comprises the amino acid sequence of SEQ ID NO: 327, and the anti-PD-1 V L comprises the amino acid sequence of SEQ ID NO: 347.

3 . The bispecific binding protein of claim 2 , wherein the PD-1 binding region is an anti-PD-1 scFv that comprises the anti-PD-1 V H and the anti-PD-1 V L .

4 . The bispecific binding protein of claim 3 , wherein the anti-PD-1 scFv comprises the amino acid sequence of SEQ ID NO: 421.

5 . The bispecific binding protein of claim 1 , wherein the anti-VEGF V H comprises the amino acid sequence of SEQ ID NO: 431, and the anti-VEGF V L comprises the amino acid sequence of SEQ ID NO: 432.

6 . The bispecific binding protein of claim 4 , wherein the anti-VEGF V H comprises the amino acid sequence of SEQ ID NO: 431, and the anti-VEGF V L comprises the amino acid sequence of SEQ ID NO: 432.

7 . The bispecific binding protein of claim 1 , further comprising an IgG1 Fc region.

8 . The bispecific binding protein of claim 6 , wherein the VEGF binding region further comprises an IgG1 Fc region.

9 . The bispecific binding protein of claim 8 , wherein the IgG1 Fc region comprises L234A/L235A (LALA) substitutions.

10 . The bispecific binding protein of claim 8 , wherein the anti-PD-1 scFv is linked to the VEGF binding region.

11 . The bispecific binding protein of claim 10 , wherein the anti-PD-1 scFv is linked to the C-terminal of the VEGF binding region.

12 . The bispecific binding protein of claim 11 , wherein the anti-PD-1 scFv is linked to the VEGF binding region directly.

13 . The bispecific binding protein of claim 11 , wherein the anti-PD-1 scFv is linked to the VEGF binding region via a linker.

14 . The bispecific binding protein of claim 13 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 1030.

15 . The bispecific binding protein of claim 1 , wherein the bispecific binding protein comprises a heavy chain that comprises the amino acid sequence of SEQ ID NO: 96, and a light chain that comprises the amino acid sequence of SEQ ID NO: 243.

16 . The bispecific binding protein of claim 1 , comprising two PD-1 binding regions and two VEGF binding regions.

17 . A pharmaceutical composition comprising the bispecific binding protein of claim 1 and a pharmaceutically acceptable carrier.

18 . A bispecific binding protein comprising a first polypeptide chain having the sequence of SEQ ID NO: 96 and a second polypeptide chain having the sequence of SEQ ID NO: 243, wherein the bispecific binding protein comprises two PD-1 binding regions and two VEGF-binding regions.

19 . A pharmaceutical composition comprising the bispecific binding protein of claim 18 and a pharmaceutically acceptable carrier.