IP Library › Granted Patent US 12,344,650
Granted Patent B2
US 12,344,650 · App. 18/046,082 · Granted Jul 1, 2025

Compositions for increasing half-life of a therapeutic agent in felines and methods of use

Inventors: William Brondyk (Mansfield, MA); Brett Chevalier (Melrose, MA); Juergen Horn (Marblehead, MA); Madhusudan Natarajan (Waban, MA)
Assignee: Invetx, Inc.
C07K14/70503A61K38/00C07K2317/52
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Quick Facts
Patent No.
US 12,344,650
App. No.
18/046,082
Granted
Jul 1, 2025
Kind
B2
Abstract

Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a feline and methods of their use. The compositions involve variant feline IgG Fc regions.

Claims (45)

1. A polypeptide comprising a feline IgG Fc region variant, wherein the polypeptide comprises (i) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is S428L, and (ii) an amino acid substitution at at least one position selected from the group consisting of:

(a) an amino acid substitution at a position that corresponds to amino acid position 286 of a wild type feline IgG, wherein the amino acid substitution is T286E;

(b) an amino acid substitution at a position that corresponds to amino acid position 311 of a wild type feline IgG, wherein the amino acid substitution is Q311V or Q311K;

(c) an amino acid substitution at a position that corresponds to amino acid position 312 of a wild type feline IgG, wherein the amino acid substitution is D312T;

(d) an amino acid substitution at a position that corresponds to amino acid position 377 of a wild type feline IgG, wherein the amino acid substitution is I377V; and

(e) an amino acid substitution at a position that corresponds to amino acid position 383 of a wild type feline IgG, wherein the amino acid substitution is I383L;

wherein the amino acid position is based on EU numbering, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3, wherein the polypeptide has increased binding affinity to feline FcRn when compared to an Fc domain of the wild type feline IgG, and wherein the polypeptide binds to feline FcRn at a higher level at pH 6.0 than at pH 7.4.

2. The polypeptide of claim 1 , wherein the polypeptide comprises:

(i) an amino acid substitution at a position that corresponds to amino acid position 286 of a wild type feline IgG, wherein the amino acid substitution is T286E; and

(ii) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is S428L.

3. The polypeptide of claim 1 , wherein the wild type feline IgG is a feline IgG1a comprising an Fc domain having an amino acid sequence of SEQ ID NO: 1.

4. The polypeptide of claim 1 , wherein the wild type feline IgG is a feline IgG1b comprising an Fc domain having an amino acid sequence of SEQ ID NO: 2.

5. The polypeptide of claim 1 , wherein the wild type feline IgG is a feline IgG2 comprising an Fc domain having an amino acid sequence of SEQ ID NO: 3.

6. The polypeptide of claim 1 , further comprising a polypeptide selected from the group consisting of EPO, CTLA4, LFA3, VEGFR1/VEGFR3, IL-IR, IL-4R, GLP-1 receptor agonist, and Thrombopoietin binding peptide.

7. The polypeptide of claim 1 , further comprising a binding domain, wherein the binding domain comprises a ligand binding domain of a feline receptor protein.

8. The polypeptide of claim 1 , further comprising a binding domain, wherein the binding domain comprises a nanobody.

9. The polypeptide of claim 1 , further comprising a binding domain, wherein the binding domain comprises an extracellular domain of a feline receptor protein.

10. A pharmaceutical composition comprising (i) the polypeptide of claim 1 , and (ii) a pharmaceutically acceptable excipient.

11. A nucleic acid or nucleic acids encoding the polypeptide of claim 1 .

12. An expression vector or expression vectors comprising the nucleic acid or nucleic acids of claim 11 .

13. A host cell comprising the nucleic acid or nucleic acids of claim 11 or an expression vector or expression vectors comprising the nucleic acid or nucleic acids.

14. A method of making a polypeptide, the method comprising:

(a) providing a nucleic acid or nucleic acids of claim 11 ;

(b) expressing the nucleic acid or nucleic acids in a host cell culture, thereby producing the polypeptide; and

(c) collecting the polypeptide produced in (b) from the host cell culture.

15. A polypeptide comprising a feline IgG Fc region variant, wherein the polypeptide comprises (i) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is S428Y, and (ii) an amino acid substitution at at least one position selected from the group consisting of:

(a) a position that corresponds to amino acid position 286 of a wild type feline IgG;

(b) a position that corresponds to amino acid position 301 of a wild type feline IgG;

(c) a position that corresponds to amino acid position 309 of a wild type feline IgG;

(d) a position that corresponds to amino acid position 311 of a wild type feline IgG; and

(e) a position that corresponds to amino acid position 377 of a wild type feline IgG;

wherein the amino acid position is based on EU numbering, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3, wherein the polypeptide has increased binding affinity to feline FcRn when compared to an Fc domain of the wild type feline IgG, and wherein the polypeptide binds to feline FcRn at a higher level at pH 6.0 than at pH 7.4.

16. The polypeptide of claim 15 , wherein the polypeptide comprises (i) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is S428Y, and (ii) one or more amino acid substitutions selected from the group consisting of:

(a) an amino acid substitution at a position that corresponds to amino acid position 286 of a wild type feline IgG, wherein the amino acid substitution is T286D;

(b) an amino acid substitution at a position that corresponds to amino acid position 301 of a wild type feline IgG, wherein the amino acid substitution is R301L;

(c) an amino acid substitution at a position that corresponds to amino acid position 309 of a wild type feline IgG, wherein the amino acid substitution is L309V or L309E;

(d) an amino acid substitution at a position that corresponds to amino acid position 311 of a wild type feline IgG, wherein the amino acid substitution is Q311L; and

(e) an amino acid substitution at a position that corresponds to amino acid position 377 of a wild type feline IgG, wherein the amino acid substitution is I377Y.

17. The polypeptide of claim 16 , wherein the polypeptide comprises:

(i) an amino acid substitution at a position that corresponds to amino acid position 309 of a wild type feline IgG, wherein the amino acid substitution is L309V; and

(ii) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is S428Y.

18. A polypeptide comprising a feline IgG Fc region variant, wherein the polypeptide comprises:

(a) an amino acid substitution at a position that corresponds to amino acid position 252 of a wild type feline IgG, wherein the amino acid substitution is S252Y; and

(b) an amino acid substitution at a position that corresponds to amino acid position 311 of a wild type feline IgG, wherein the amino acid substitution is Q311V, Q311L, Q311R, or Q311K;

wherein the amino acid position is based on EU numbering, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3, wherein the polypeptide has increased binding affinity to feline FcRn when compared to an Fc domain of the wild type feline IgG, and wherein the polypeptide binds to feline FcRn at a higher level at pH 6.0 than at pH 7.4.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 22, 2023
From: BRONDYK, WILLIAM; CHEVALIER, BRETT; HORN, JUERGEN; NATARAJAN, MADHUSUDAN
To: INVETX, INC.
Reel/Frame 062763/0022 →
Continuity (4)
Continuation 17355839 · Jun 23, 2021
Provisional Application 63143720 · Jan 29, 2021
Provisional Application 63050535 · Jul 10, 2020
Related Publication 20230090405A1 · Mar 23, 2023
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