IP Library › Granted Patent US 12,077,601

Granted Patent B2

US 12,077,601 · App. 17/379,739 · Granted Sep 3, 2024

Antibodies to ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) and related methods

Inventors: Michael Catania (San Diego, CA); Ronald L. Hayes (San Diego, CA)

C07K16/40 A61B5/0042 A61B5/055 A61B6/032 A61B6/501 A61P25/00 C07K16/18 G01N33/6896 C07K2317/20 C07K2317/21 C07K2317/34 C07K2317/52 C07K2317/565 C07K2317/76 C07K2317/92

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Quick Facts

Patent No.: US 12,077,601
App. No.: 17/379,739
Granted: Sep 3, 2024
Kind: B2

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Abstract

The invention provides anti-UCH-L1 antibodies and anti-GFAP antibodies and their use in in vitro detection of UCH-L1 and GFAP, respectively, in a sample from an individual, such as an individual known or suspected of having a brain injury or damage, for example, neurological damage such as mild traumatic brain injury. Also provided are methods, systems and kits for diagnosing brain injury or damage, such as neurological damage, in an individual with the aforementioned antibodies as well as compositions comprising the anti-UCH-L1 antibodies and anti-GFAP antibodies.

Claims (79)

1. An antibody or antigen-binding fragment thereof that specifically binds to a human ubiquitin c-terminal hydrolase L1 (UCH-L1) protein, comprising:

a heavy chain variable region that comprises CDR-H1, CDR-H2, and CDR-H3 amino acid sequences; and

a light chain variable region that comprises CDR-L1, CDR-L2, and CDR-L3 amino acid sequences,

wherein:

(1) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:2, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:10, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:21; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:29, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:38, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:46; or

(2) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:5, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:13, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:23; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:32, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:39, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:47; or

(3) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:3, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:11, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:20; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:30, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:37, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:45; or

(4) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:4, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:12, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:22; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:31, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:39, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:47; or

(5) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:14, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:33, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:40, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:48; or

(6) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:14, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:34, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:41, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:48; or

(7) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:15, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:34, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:42, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:48; or

(8) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:14, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:35, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:41, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:48; or

(9) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:16, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:25; and

(10) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:7, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:17, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:26; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:36, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:43, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:49; or

(11) the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:8, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:18, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:27; and

the light chain variable region comprises (i) the CDR-L1 amino acid sequence comprising SEQ ID NO:36, (ii) the CDR-L2 amino acid sequence comprising SEQ ID NO:44, and (iii) the CDR-L3 amino acid sequence comprising SEQ ID NO:49.

2. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:2, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:10, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:21; and

3. The antibody or antigen-binding fragment of claim 2 , wherein:

the heavy chain variable region comprises SEQ ID NO:52; and

the light chain variable region comprises SEQ ID NO:65.

4. A method of detecting a human ubiquitin c-terminal hydrolase L1 (UCH-L1) protein, comprising:

obtaining a biological sample collected from a human subject;

contacting the biological sample with the antibody or antigen-binding fragment of claim 2 under conditions that form a complex comprising the antibody or antigen-binding fragment and UCH-L1; and

detecting the complex in the biological sample so as to detect UCH-L1.

5. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:5, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:13, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:23; and

6. The antibody or antigen-binding fragment of claim 5 , wherein:

the heavy chain variable region comprises SEQ ID NO:55; and

the light chain variable region comprises SEQ ID NO:68.

7. A method of detecting a human ubiquitin c-terminal hydrolase L1 (UCH-L1) protein, comprising:

obtaining a biological sample collected from a human subject;

contacting the biological sample with the antibody or antigen-binding fragment of claim 5 under conditions that form a complex comprising the antibody or antigen-binding fragment and UCH-L1; and

detecting the complex in the biological sample so as to detect UCH-L1.

8. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:3, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:11, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:20; and

9. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:4, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:12, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:22; and

10. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:14, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

11. The antibody or antigen-binding fragment of claim 1 , wherein:

12. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:15, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:24; and

13. The antibody or antigen-binding fragment of claim 1 , wherein:

14. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:6, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:16, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:25; and

15. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:7, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:17, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:26; and

16. The antibody or antigen-binding fragment of claim 1 , wherein:

the heavy chain variable region comprises (i) the CDR-H1 amino acid sequence comprising SEQ ID NO:8, (ii) the CDR-H2 amino acid sequence comprising SEQ ID NO:18, and (iii) the CDR-H3 amino acid sequence comprising SEQ ID NO:27; and

17. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds UCH-L1 with a dissociation constant (K D ) of less than about 1.0×10 −10 M.

18. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds UCH-L1 with a dissociation constant (K D ) of from about 2.0×10 −10 M to 1.0×10 −12 M.

19. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds to an epitope within or that is or includes residues 28-36 of the UCH-L1 protein, residues 98-106 of the UCH-L1 protein, residues 138-145 of the UCH-L1 protein, and/or residues 142-149 of the UCH-L1 protein corresponding to amino acid positions set forth in SEQ ID NO:207.

20. An antibody or antigen-binding fragment thereof that specifically binds to a human ubiquitin c-terminal hydrolase L1 (UCH-L1) protein, comprising:

a heavy chain variable region that comprises any of SEQ ID NOs:52-62; and

a light chain variable region that comprises any of SEQ ID NOs:65-75.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2026

From: BANYAN BIOMARKERS, INC.

To: BIOMERIEUX, INC.

Reel/Frame 074323/0554 →

CHANGE OF ADDRESS OF ASSIGNEE Recorded Nov 12, 2024

From: BANYAN BIOMARKERS, INC.

To: BANYAN BIOMARKERS, INC.

Reel/Frame 069340/0120 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 4, 2021

From: CATANIA, MICHAEL; HAYES, RONALD L

To: BANYAN BIOMARKERS, INC.

Reel/Frame 057083/0429 →

Continuity (3)

Division 16345562

Provisional Application 62414569 · Oct 28, 2016

Related Publication 20210347914A1 · Nov 11, 2021