Granted Patent B2

US 12,358,978 · App. 17/413,269 · Granted Jul 15, 2025

Inventors: Jonathan Hill (Cambridge, MA); Scott Chappel (Cambridge, MA); Michael Gladstone (Cambridge, MA); Bianka Prinz (Lebanon, NH); Andrew Lake (Cambridge, MA); Christine Miller (Cambridge, MA); Kerry White (Cambridge, MA); Jing Hua (Cambridge, MA); Pamela M. Holland (Cambridge, MA); Matthew Rausch (Cambridge, MA); Devapregasan Moodley (Cambridge, MA); Gege Tan (Cambridge, MA)

Assignee: SURFACE ONCOLOGY, LLC

C07K16/244A61P35/00A61P37/04C07K16/24C07K16/2803C07K16/2827C07K16/2851G01N33/574A61K2039/505C07K2317/24C07K2317/33C07K2317/34C07K2317/565C07K2317/76C07K2317/92G01N2333/54

Abstract

Claims (49)

1. A monoclonal antibody that specifically binds human IL-27, or antigen binding portion thereof, wherein the antibody or antigen binding portion thereof comprises heavy and light chain CDRs selected from the group consisting of:

(i) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 706, 707 and 708, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 714, 715 and 716, respectively;

(ii) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 728, 729 and 730, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 736, 737 and 738, respectively;

(iii) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 750, 751 and 752, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 758, 759 and 760, respectively;

(iv) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 772, 773 and 774, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 780, 781 and 782, respectively;

(v) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 709, 710 and 711, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 717, 718 and 719, respectively;

(vi) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 731, 732 and 733, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 739, 740 and 741, respectively;

(vii) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 753, 754 and 755, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 761, 762 and 763, respectively; and

(viii) heavy chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 775, 776 and 777, respectively, and light chain CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 783, 784 and 785, respectively.

2. The monoclonal antibody, or antigen binding portion thereof, of claim 1 , wherein the antibody or antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequences at least 90% identical to the amino acid sequences selected from the group consisting of:

(i) SEQ ID NO: 712 and 720, respectively;

(ii) SEQ ID NO: 734 and 742, respectively;

(iii) SEQ ID NO: 756 and 764, respectively; and

(iv) SEQ ID NO: 778 and 786, respectively.

3. The monoclonal antibody, or antigen binding portion thereof, of claim 1 wherein:

(i) the antibody, or antigen binding portion thereof, antagonizes IL-27;

(ii) the antibody, or antigen binding portion thereof, inhibits or reduces STAT1 and/or STAT3 phosphorylation in a cell, optionally wherein the cell is an immune cell or a cancer cell;

(iii) the antibody, or antigen binding portion thereof, inhibits or reduces inhibition of CD161 expression in a cell;

(iv) the antibody or antigen binding portion thereof inhibits or reduces PD-L1 and/or TIM-3 expression in a cell;

(v) the antibody, or antigen binding portion thereof, induces or enhances the PD-1-mediated secretion of one or more cytokines from a cell, optionally wherein the one or more cytokines is IFNγ, IL-17, TNFα and/or IL-6; or

(vi) any combination of (i)-(v).

4. The monoclonal antibody, or antigen binding portion thereof, of claim 1 , wherein the antibody comprises (i) a wild type IgG1 heavy chain constant region, (ii) a wild type IgG4 heavy chain constant region, (iii) a mutant IgG1 heavy chain constant region, or (iv) a mutant IgG4 heavy chain constant region.

5. The monoclonal antibody, or antigen binding portion thereof, of claim 4 , wherein the mutant IgG4 heavy chain constant region comprises any one of the substitutions S228P, L235E, L235A, or a combination thereof, according to EU numbering.

6. A pharmaceutical composition comprising the monoclonal antibody, or antigen binding portion thereof, of claim 1 , and a pharmaceutically acceptable carrier.

7. A method of detecting IL-27, in a sample from a subject, comprising (a) contacting a sample from the subject with a detection antibody under conditions to permit the detection antibody to form a detection antibody-IL-27 complex, if IL-27 is present in the sample; and (b) detecting the presence of the complex, if any, produced in step (a); wherein the detection antibody comprises the antibody, or antigen binding portion thereof, of claim 1 .

8. The method of claim 7 , further comprising contacting the sample with a capture antibody to produce a complex comprising IL-27 and the capture antibody, if IL-27 is present in the sample.

9. The method of claim 8 , wherein the capture antibody comprises:

(i) a heavy CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 23,

(ii) a heavy CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 24,

(iii) a heavy CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 25,

(iv) a light CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 26,

(v) a light CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 27, and

(vi) a light CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28.

10. The method of claim 7 , wherein the detection antibody is coupled to a detectable label.

11. The method of claim 8 , wherein the capture antibody is immobilized on a solid support.

12. The method of claim 8 , wherein the sample is contacted with the capture antibody before the detection antibody.

13. The method of claim 7 , wherein the sample is a body fluid sample.

14. The method of claim 13 , wherein the fluid sample is blood, serum, plasma, cell lysates or tissue lysates.

15. The monoclonal antibody, or antigen binding portion thereof, of claim 1 , wherein the heavy chain CDR1, CDR2 and CDR3 sequences are set forth in SEQ ID NOs: 706, 707 and 708, respectively, and the light chain CDR1, CDR2 and CDR3 sequences are set forth in SEQ ID NOs: 714, 715 and 716, respectively.

16. The monoclonal antibody, or antigen binding portion thereof, of claim 1 , wherein the antibody or antigen binding portion thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequences at least 90% identical to SEQ ID NOs: 712 and 720, respectively.

17. The monoclonal antibody, or antigen binding portion thereof, of claim 1 , wherein the antibody or antigen binding portion thereof comprises a heavy chain and a light chain comprising amino acid sequences at least 90% identical to the amino acid sequences selected from the group consisting of:

(i) SEQ ID NO: 722 and 724, respectively;

(ii) SEQ ID NO: 744 and 746, respectively;

(iii) SEQ ID NO: 766 and 768, respectively;

(iv) SEQ ID NO: 788 and 790, respectively;

(v) SEQ ID NO: 726 and 724, respectively;

(vi) SEQ ID NO: 748 and 746, respectively;

(vii) SEQ ID NO: 770 and 768, respectively; and

(viii) SEQ ID NO: 792 and 790, respectively.

Assignments (6)

Continuity (2)

References Cited (234)