PET imaging with PD-L1 binding polypeptides

Patent metadata

Field	Value
Publication number	US-11344639-B2
Application number	US-201716305284-A
Country	US
Kind code	B2
Filing date	May 31, 2017
Priority date	Jun 1, 2016
Publication date	May 31, 2022
Grant date	May 31, 2022

Abstract

Provided herein are novel 10 Fn3 domains which specifically bind to PD-L1, as well as imaging agents based on the same for diagnostics.

First claim

We claim:

1. A method of visualizing Programmed Death Ligand-1 (PD-L1) protein in a subject, comprising:
(a) administering to the subject a radiolabeled PD-L1 imaging agent at a dose of about 3-10 mCi (100-333 MBq);
(b) conducting a PET scan of the subject about 30-120 minutes after administering the imaging agent and obtaining an image; and
(c) visualizing the presence of the PD-L1 protein in the subject from the image,

wherein the imaging agent comprises a radiolabeled prosthetic group conjugated to an anti-PD-L1 adnectin by a bifunctional chelating agent, wherein the radiolabeled prosthetic group has the following structure:

wherein the 18 F is ortho to the N atom, x is an integer from 1 to 8, and wherein the anti-PD-L1 adnectin comprises BC, DE, and FG loops comprising amino acid sequences selected from the group consisting of:
(i) SEQ ID NOs: 6, 7, and 8, respectively;
(ii) SEQ ID NOs: 21, 22, and 23, respectively;
(iii) SEQ ID NOs: 36, 37, and 38, respectively;
(iv) SEQ ID NOs: 51, 52, and 53, respectively;
(v) SEQ ID NOs: 66, 67, and 68, respectively;
(vi) SEQ ID NOs: 81, 82, and 83, respectively; or
(vii) SEQ ID NOs: 97, 98, and 99, respectively.

2. The method of claim 1 , wherein the subject has at least one tumor.

3. The method of claim 2 , comprising comparing the uptake of the imaging agent in the at least one tumor and in background tissue, wherein the presence of PD-L1 in the at least one tumor above the background tissue is indicative that the PD-L1 is expressed in the at least one tumor and that the subject is likely to respond to treatment with a PD-1 or PD-L1 antagonist.

4. The method of claim 1 , wherein the radiolabel is a radioactive PET tracer.

5. The method of claim 1 , wherein the anti-PD-L1 adnectin comprises an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 5, 20, 35, 50, 65, 80 or 96.

6. The method of claim 1 , wherein the anti-PD-L1 adnectin comprises an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 9-15, 24-30, 39-45, 54-60, 69-75, 84-91, and 100-107.

7. The method of claim 1 , wherein the structure of the 18 F-radiolabeled prosthetic group is,

8. The method of claim 1 , wherein the structure of the 18 F-radiolabeled prosthetic group is,

9. The method of claim 1 , wherein the structure of the 18 F-radiolabeled prosthetic group is

10. The method of claim 1 , wherein the bifunctional chelating agent is a cyclooctyne comprising a reactive group that forms a covalent bond with an amine, carboxyl, carbonyl or thiol functional group on the protein.

11. The method of claim 1 , wherein the imaging agent has a structure as set forth below:

wherein X is an anti-PD-L1 adnectin comprising the amino acid sequence of any one of SEQ ID NOs: 13, 28, 43, 58, 73, 88, and 104.

12. The method of claim 11 , wherein the anti-PD-L1 adnectin comprises the amino acid sequence set forth in SEQ ID NO: 88.

13. The method of claim 11 , wherein the anti-PD-L1 adnectin comprises the amino acid sequence set forth in SEQ ID NO: 104.

Assignees

• Bristol Myers Squibb Co

Inventors

• Morin Paul E
• Donnelly David
• Lipovsek Dasa
• Gokemeijer Jochem
• Jure-Kunkel Maria
• Fabrizio David
• Wright Martin C
• Dischino Douglas
• Bonacorsi Jr Samuel J
• Smith Ralph Adam
• Lafont Virginie
• Cohen Daniel
• Leung David K

Classifications

• A61K51/0455

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title

• A61K51/088 Primary

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K2123/00

  Preparations for testing in vivo · CPC title