Modified amino acids

• US 10,730,837 B2
• Filed: 10/29/2018
• Issued: 08/04/2020
• Est. Priority Date: 08/31/2012
• Status: Active Grant

• Current Assignee: Sutro Biopharma, Inc.
• Original Assignee: Sutro Biopharma, Inc.
• Inventors: Stafford, Ryan, Thanos, Christopher D., Yang, Wenjin
• Primary Examiner(s): Northington Davis, Zinna
• Application Number:
  US16/173,968
• Publication Number:
  US 20190047958A1
• Time in Patent Office: 645 Days
• Field of Search: None
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07C 247/04 being saturated
• CPC Class Codes: C07C 271/20 to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07C 275/14 being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07D 213/55 Acids; Esters
• CPC Class Codes: C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C07K 14/535 Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002

Abstract

Provided herein are modified amino acids comprising an azido group, polypeptides, antibodies and conjugates comprising the modified amino acids, and methods of producing the polypeptides, antibodies and conjugates comprising the modified amino acids. The polypeptides, antibodies and conjugates are useful in methods of treatment and prevention, methods of detection and methods of diagnosis.

Claims

1. A polypeptide-linked-to-a-payload comprising a polypeptide and a payload and optionally comprising a linking moiety between the polypeptide and the payload wherein the polypeptide comprises one or more amino acid residues according to the following formula:

2. The polypeptide-linked-to-a-payload of claim 1, wherein W₄ is C₁ alkylene.

3. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is selected from the group consisting of:

alpha-1 antitrypsin, angiostatin, antihemolytic factor, antibody, apolipoprotein, apoprotein, atrial natriuretic factor, atrial natriuretic polypeptide, atrial peptide, C-X-C chemokine, T39765, NAP-2, ENA-78, gro-a, gro-b, gro-c, IP-10, GCP-2, NAP-4, SDF-1, PF4, MIG, calcitonin, c-kit ligand, cytokine, CC chemokine, monocyte chemoattractant protein-1, monocyte chemoattractant protein-2, monocyte chemoattractant protein-3, monocyte inflammatory protein-1 alpha, monocyte inflammatory protein-1beta, RANTES, 1309, R83915, R91733, HCC1, T58847, D31065, T64262, CD40, CD40 ligand, c-kit ligand, collagen, colony stimulating factor (CSF), complement factor 5a, complement inhibitor, complement receptor 1, cytokine, epithelial neutrophil activating peptide-78, MIP-16, MCP-1, epidermal growth factor (EGF), epithelial neutrophil activating peptide, erythropoietin (EPO), exfoliating toxin, Factor IX, Factor VII, Factor VIII, Factor X, fibroblast growth factor (FGF), fibrinogen, fibronectin, four-helical bundle protein, G-CSF, glp-1, GM-CSF, glucocerebrosidase, gonadotropin, growth factor, growth factor receptor, grf, hedgehog protein, hemoglobin, hepatocyte growth factor (hGF), hirudin, human growth hormone (hGH), human serum albumin, ICAM-1, ICAM-1 receptor, LFA-1, LFA-1 receptor, insulin, insulin-like growth factor (IGF), IGF-I, IGF-II, interferon (IFN), IFN-alpha, IFN-beta, IFN-gamma, interleukin (IL), IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, keratinocyte growth factor (KGF), lactoferrin, leukemia inhibitory factor, luciferase, neurturin, neutrophil inhibitory factor (NIF), oncostatin M, osteogenic protein, oncogene product, paracitonin, parathyroid hormone, PD-ECSF, PDGF, peptide hormone, pleiotropin, protein A, protein G, pth, pyrogenic exotoxin A, pyrogenic exotoxin B, pyrogenic exotoxin C, pyy, relaxin, renin, SCF, small biosynthetic protein, soluble complement receptor I, soluble I-CAM 1, soluble interleukin receptor, soluble TNF receptor, somatomedin, somatostatin, somatotropin, streptokinase, superantigens, staphylococcal enterotoxin, SEA, SEB, SECT, SEC2, SEC3, SED, SEE, steroid hormone receptor, superoxide dismutase, toxic shock syndrome toxin, thymosin alpha 1, tissue plasminogen activator, tumor growth factor (TGF), tumor necrosis factor, tumor necrosis factor alpha, tumor necrosis factor beta, tumor necrosis factor receptor (TNFR), VLA-4 protein, VCAM-1 protein, vascular endothelial growth factor (VEGF), urokinase, mos, ras, raf, met, p53, tat, fos, myc, jun, myb, rel, estrogen receptor, progesterone receptor, testosterone receptor, aldosterone receptor, LDL receptor, and corticosterone.

4. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is a cytokine.

5. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is IL-2.

6. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is G-CSF.

7. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is HGH.

8. The polypeptide-linked-to-a-payload of claim 2, wherein the polypeptide is an IFN-alpha.

9. The polypeptide-linked-to-a-payload of claim 2, wherein the payload is a water soluble polymer.

10. The polypeptide-linked-to-a-payload of claim 2, wherein the payload comprises a poly(alkylene glycol);

a polyethylene glycol;

poly(dextran);

poly(propylene glycol);

XO—

(CH₂CH₂O)_n—

CH₂CH₂—

where n is an integer selected from 2 to 10,000, and X is H or C_1-4 alkyl;

or R^zO—

(CH₂CH₂O)_n1-O—

(CH₂)_m1—

;

R^zO—

(CH₂CH₂O)_n1-O—

(CH₂)_m1—

NH—

C(O)—

(CH₂)_p1—

, or [R^zO—

(CH₂CH₂O)_n1-O—

(CH₂)₂—

NH—

C(O)]₂CH(CH₂)_m1—

X¹⁰ —

(CH₂)_p1—

where R^z is alkyl, ml is 2-10, n1 is 100-1,000, p1 is 2-10, and X¹⁰ is optionally an O, N, S or carbonyl group.

11. The polypeptide-linked-to-a-payload of claim 2, wherein the payload is a poly(alkylene glycol).

12. The polypeptide-linked-to-a-payload of claim 11, wherein the payload comprises a branched poly(alkylene glycol).

13. The polypeptide-linked-to-a-payload of claim 11, wherein the payload comprises a linear poly(alkylene glycol).

14. The polypeptide-linked-to-a-payload of claim 12, wherein the payload further comprises a linear poly(alkylene glycol).

15. The polypeptide-linked-to-a-payload of claim 14, wherein the linear poly(alkylene glycol) is a poly(ethylene glycol) (PEG).

16. The polypeptide-linked-to-a-payload of claim 2, wherein the water soluble polymer comprises a degradable linkage.

17. The polypeptide-linked-to-a-payload of claim 16, wherein the degradable linkage comprises an ester.

18. The polypeptide-linked-to-a-payload of claim 2, wherein the linking moiety comprises a hydrolytically stable linkage.

19. The polypeptide-linked-to-a-payload of claim 2, wherein the linking moiety comprises a hydrolytically degradable linkage.

20. The polypeptide-linked-to-a-payload of claim 19, wherein the hydrolytically degradable linkage comprises an ester linkage, a carbonate linkage, an imine linkage;

a phosphate ester linkage, a hydrazone linkage, an acetal linkage, an orthoester linkage, a peptide linkage, or an oligonucleotide linkage.

21. The polypeptide-linked-to-a-payload of claim 2, wherein the linking moiety comprises a peptide linkage.

22. The polypeptide-linked-to-a-payload of claim 2, wherein the linking moiety comprises C_1-18-alkylene, substituted C_1-18-alkylene, hetero-C_1-18-alkylene, substituted hetero-C_1-18-alkylene, arylene, substituted arylene, heteroarlyene, or substituted heteroarylene.

23. The polypeptide-linked-to-a-payload of claim 2, wherein the half-life of the polypeptide linked to a payload is increased at least about 10, 20, 30, 40, or 50 percent, or at least about 2-fold, 5-fold, or 10-fold over an unmodified polypeptide.

24. The polypeptide-linked-to-a-payload of claim 1 prepared by contacting an alkyne-containing payload with a polypeptide comprising one or more amino acid residues according to the following formula:

25. The polypeptide-linked-to-a-payload of claim 24, wherein W₄ is C₁ alkylene.

26. The polypeptide-linked-to-a-payload of claim 25, wherein the 1,2,3-triazolylene-containing moiety is linked to the payload by a linking moiety.

27. The polypeptide-linked-to-a-payload of claim 25, wherein the 1,2,3-triazolylene moiety is linked at the 1-position of the 1,2,3-triazolylene to the W₄ position of the one or more amino acid residues.