IP Library › Granted Patent US 12,427,201
Granted Patent B2
US 12,427,201 · App. 16/572,557 · Granted Sep 30, 2025

Anti-folate receptor antibody conjugates, compositions comprising anti-folate receptor antibody conjugates, and methods of making and using anti-folate receptor antibody conjugates

Inventors: Ryan Stafford (Emeryville, CA); Alice Yam (Tiburon, CA); Xiaofan Li (Fremont, CA); Gang Yin (South San Francisco, CA); Toni Kline (San Francisco, CA); Cristina Abrahams (Burlingame, CA); Venita De Almeida (San Carlos, CA)
Assignee: Sutro Biopharma, Inc.
A61K47/6803A61K9/19A61K38/06A61K39/3955A61K47/68033A61K47/6811A61K47/6849A61K47/6851A61K47/6889A61P35/00C07K16/28A61K31/537A61K31/5545A61K38/08A61K38/12A61K47/6425A61K47/6877C07D487/00C07K2317/60C07K2317/92
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Quick Facts
Patent No.
US 12,427,201
App. No.
16/572,557
Granted
Sep 30, 2025
Kind
B2
Abstract

The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods.

Claims (70)

1. An antibody conjugate comprising an antibody of the IgG class wherein the antibody specifically binds to folate receptor alpha (FOLR1) linked site-specifically to at least one payload moiety, wherein the antibody comprises, and wherein the antibody comprises:

(i) a VH comprising: a CDR-H1 comprising SEQ ID NO: 19; a CDR-H2 comprising SEQ ID NO: 137; a CDR-H3 comprising SEQ ID NO: 255; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(ii) a V H comprising: a CDR-H1 comprising SEQ ID NO:78; a CDR-H2 comprising SEQ ID NO: 196; a CDR-H3 comprising SEQ ID NO: 255; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(iii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 4; a CDR-H2 comprising SEQ ID NO: 122; and a CDR-H3 comprising SEQ ID NO: 240; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(iv) a V H comprising: a CDR-H1 comprising SEQ ID NO:63; a CDR-H2 comprising SEQ ID NO: 181; a CDR-H3 comprising SEQ ID NO: 240; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(v) a V H comprising: a CDR-H1 comprising SEQ ID NO: 8; a CDR-H2 comprising SEQ ID NO: 126; and a CDR-H3 comprising SEQ ID NO: 244; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(vi) a V H comprising: a CDR-H1 comprising SEQ ID NO:67; a CDR-H2 comprising SEQ ID NO: 185; a CDR-H3 comprising SEQ ID NO: 244; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(vii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 12; a CDR-H2 comprising SEQ ID NO: 130; and a CDR-H3 comprising SEQ ID NO: 248; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(viii) a V H comprising: a CDR-H1 comprising SEQ ID NO:71; a CDR-H2 comprising SEQ ID NO: 189; a CDR-H3 comprising SEQ ID NO: 248; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(ix) a V H comprising: a CDR-H1 comprising SEQ ID NO: 14; a CDR-H2 comprising SEQ ID NO: 132; and a CDR-H3 comprising SEQ ID NO: 250; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(x) a V H comprising: a CDR-H1 comprising SEQ ID NO:73; a CDR-H2 comprising SEQ ID NO: 191; a CDR-H3 comprising SEQ ID NO: 250; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xi) a V H comprising: a CDR-H1 comprising SEQ ID NO: 56; a CDR-H2 comprising SEQ ID NO: 174; and a CDR-H3 comprising SEQ ID NO: 292; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xii) a V H comprising: a CDR-H1 comprising SEQ ID NO:115; a CDR-H2 comprising SEQ ID NO: 233; a CDR-H3 comprising SEQ ID NO: 292; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xiii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 58; a CDR-H2 comprising SEQ ID NO: 176; and a CDR-H3 comprising SEQ ID NO: 294; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305; or

(xiv) a V H comprising: a CDR-H1 comprising SEQ ID NO:117; a CDR-H2 comprising SEQ ID NO: 235; a CDR-H3 comprising SEQ ID NO: 294; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305.

2. The antibody conjugate of claim 1 , wherein the antibody comprises:

(i) the V H region SEQ ID NO: 323, and the V L region SEQ ID NO: 367;

(ii) the V H region SEQ ID NO: 308, and the V L region SEQ ID NO: 367

(vi) the V H region SEQ ID NO: 312, and the V L region SEQ ID NO: 367;

(x) the V H region SEQ ID NO: 316, and the V L region SEQ ID NO: 367

(xii) the V H region SEQ ID NO: 318, and the V L region SEQ ID NO: 367;

(liii) the V H region SEQ ID NO: 360, and the V L region SEQ ID NO: 367; or

(lix) the V H region SEQ ID NO: 362, and the V L region SEQ ID NO: 369.

3. The antibody conjugate of claim 1 , wherein the antibody further comprises one or more non-natural amino acids, and wherein the one or more non-natural amino acids is selected from the group consisting of p-acetyl-L-phenylalanine, O-methyl-L-tyrosine, an -3-(2-naphthyl) alanine, 3-methyl-phenylalanine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, a tri-O-acetyl-GlcNAcß-serine, L-Dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L-phenylalanine, p-azido-methyl-L-phenylalanine, compound (30):

compound (56): p

-acyl-L-phenylalanine, p-benzoyl-L-phenylalanine, L-phosphoserine, phosphonoserine, phosphonotyrosine, p-iodo-phenylalanine, p-bromophenylalanine, p-amino-L-phenylalanine, isopropyl-L-phenylalanine, and p-propargyloxy-phenylalanine.

4. The antibody conjugate of claim 3 , wherein a residue of the one or more non-natural amino acids is linked to the payload moiety via a linker that is cleavable.

5. The antibody conjugate of claim 3 , wherein the non-natural amino acid residue is a residue of compound (30):

or of compound (56):

6. The antibody conjugate of claim 3 , wherein the payload moiety is selected from the group consisting of maytansines, hemiasterlins, amanitins, and auristatins.

7. The antibody conjugate of claim 3 , wherein the payload moiety is selected from the group consisting of DM1, hemiasterlin, amanitin, MMAF, and MMAE.

8. The antibody conjugate of claim 3 , wherein the antibody comprises a V H region comprising SEQ ID NO: 362, or a variant thereof having 7 or fewer amino acid substitutions, and a V L region comprising SEQ ID NO: 367, or a variant thereof having 7 or fewer amino acid substitutions.

9. The antibody of claim 8 , wherein the amino acid substitutions are conservative amino acid substitutions.

10. The antibody conjugate of claim 3 , wherein the antibody comprises a non-natural amino acid at site HC-F404.

11. The antibody conjugate of claim 3 , wherein the antibody comprises non-natural amino acids at sites HC-F404 and HC-Y180.

12. The antibody conjugate of claim 3 , wherein the antibody comprises non-natural amino acids at sites HC-F404 and LC-K42.

13. The antibody conjugate of claim 10 , wherein the non-natural amino acids are selected from the group consisting of para-azidomethylphenylalanine and p-azido-methyl-L-phenylalanine.

14. The antibody conjugate of claim 11 , wherein the non-natural amino acids are selected from the group consisting of para-azidomethylphenylalanine and para-azido-methyl-L-phenylalanine.

15. The antibody conjugate of claim 3 , wherein the antibody conjugate has the structure of Conjugate P:

wherein n is an integer from 1 to 6.

16. The antibody conjugate of claim 3 , wherein the antibody conjugate has the structure of Conjugate M:

wherein n is an integer from 1 to 6.

17. The antibody conjugate of claim 3 , wherein the antibody conjugate has the structure of Conjugate Q:

wherein n is an integer from 1 to 6.

18. The antibody conjugate of claim 1 , further comprising at least one constant region domain comprising a sequence selected from SEQ ID NOs: 370, 371, and 372.

19. The antibody conjugate of claim 1 , wherein the antibody is humanized or human.

20. The antibody conjugate of claim 1 , wherein the antibody is aglycosylated.

21. The antibody conjugate of claim 1 , wherein the antibody is an antibody fragment selected from the group consisting of: an Fv fragment, a Fab fragment, a F (ab′) 2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment.

22. A pharmaceutical composition comprising the antibody conjugate of claim 1 and a pharmaceutically acceptable carrier.

23. A method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody conjugate of claim 1 .

24. A method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of, or a pharmaceutical composition of claim 22 .

25. The method of claim 22 , wherein the disease or condition is selected from the group consisting of: triple-negative breast cancer (TNBC), ovarian cancer, and endometrial cancer.

26. The antibody conjugate of claim 1 , wherein the antibody comprises one or more non-natural amino acids at sites selected from the group consisting of: HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme.

27. An antibody conjugate comprising an antibody of the IgG class, said antibody comprising:

(i) a V H comprising: a CDR-H1 comprising SEQ ID NO: 19; a CDR-H2 comprising SEQ ID NO: 137; a CDR-H3 comprising SEQ ID NO: 255; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(ii) a V H comprising: a CDR-H1 comprising SEQ ID NO:78; a CDR-H2 comprising SEQ ID NO: 196; a CDR-H3 comprising SEQ ID NO: 255; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(iii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 4; a CDR-H2 comprising SEQ ID NO: 122; and a CDR-H3 comprising SEQ ID NO: 240; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(iv) a V H comprising: a CDR-H1 comprising SEQ ID NO:63; a CDR-H2 comprising SEQ ID NO: 181; a CDR-H3 comprising SEQ ID NO: 240; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(v) a V H comprising: a CDR-H1 comprising SEQ ID NO: 8; a CDR-H2 comprising SEQ ID NO: 126; and a CDR-H3 comprising SEQ ID NO: 244; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(vi) a V H comprising: a CDR-H1 comprising SEQ ID NO:67; a CDR-H2 comprising SEQ ID NO: 185; a CDR-H3 comprising SEQ ID NO: 244; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(vii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 12; a CDR-H2 comprising SEQ ID NO: 130; and a CDR-H3 comprising SEQ ID NO: 248; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(viii) a V H comprising: a CDR-H1 comprising SEQ ID NO:71; a CDR-H2 comprising SEQ ID NO: 189; a CDR-H3 comprising SEQ ID NO: 248; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(ix) a V H comprising: a CDR-H1 comprising SEQ ID NO: 14; a CDR-H2 comprising SEQ ID NO: 132; and a CDR-H3 comprising SEQ ID NO: 250; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(x) a V H comprising: a CDR-H1 comprising SEQ ID NO:73; a CDR-H2 comprising SEQ ID NO: 191; a CDR-H3 comprising SEQ ID NO: 250; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xi) a V H comprising: a CDR-H1 comprising SEQ ID NO: 56; a CDR-H2 comprising SEQ ID NO: 174; and a CDR-H3 comprising SEQ ID NO: 292; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xii) a V H comprising: a CDR-H1 comprising SEQ ID NO:115; a CDR-H2 comprising SEQ ID NO: 233; a CDR-H3 comprising SEQ ID NO: 292; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305;

(xiii) a V H comprising: a CDR-H1 comprising SEQ ID NO: 58; a CDR-H2 comprising SEQ ID NO: 176; and a CDR-H3 comprising SEQ ID NO: 294; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305; or

(xiv) a V H comprising: a CDR-H1 comprising SEQ ID NO:117; a CDR-H2 comprising SEQ ID NO: 235; a CDR-H3 comprising SEQ ID NO: 294; and a V L comprising: a CDR-L1 comprising SEQ ID NO: 299; a CDR-L2 comprising SEQ ID NO: 302; and a CDR-L3 comprising SEQ ID NO: 305,

linked site-specifically to at least one payload moiety, and wherein the antibody conjugate has the structure of Conjugate P:

wherein n is an integer from 1 to 6.

Continuity (3)
Continuation 16133383 · Sep 17, 2018
Provisional Application 62560064 · Sep 18, 2017
Related Publication 20200147229A1 · May 14, 2020
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