Protein-polymer-drug conjugates

Patent metadata

Field	Value
Publication number	US-11434278-B2
Application number	US-201916382735-A
Country	US
Kind code	B2
Filing date	Apr 12, 2019
Priority date	Oct 11, 2013
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

First claim

What is claimed is:

1. A therapeutic drug and targeting conjugate useful in anti-neoplastic therapies comprising an anti-5T4 ligand, the ligand comprising an immunoglobulin or functional fragment which is an anti-5T4 scFvFc, and a poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF) polymeric scaffold comprising the units shown below which may be randomly connected to each other,

wherein:
ANTI-5T4 is a single chain antibody construct comprising the amino sequence designated as SEQ ID NO: 7;
the sulfur atom is part of the single chain antibody construct;
the PHF has a molecular weight ranging from about 2 kDa to about 40 kDa;
the average polymeric scaffold to anti-5T4 single chain antibody ratio is about 2:1 to about 4:1; and
the auristatin F HPA to anti-5T4 antibody ratio is about 8:1 to about 13:1.

2. A pharmaceutical composition comprising a therapeutic drug and targeting conjugate of claim 1 and a pharmaceutically acceptable carrier.

3. A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 2 .

4. The method of claim 3 , wherein the cancer is selected from the group consisting of anal, astrocytoma, leukemia, lymphoma, head and neck, liver, testicular, cervical, sarcoma, hemangioma, esophageal, eye, laryngeal, mouth, mesothelioma, skin, myeloma, oral, rectal, throat, bladder, breast, uterus, ovary, prostate, lung, colon, pancreas, renal, and gastric cancer.

Assignees

• Asana Biosciences Llc

Inventors

• Smith Roger A
• Damle Nitin K
• Yurkovetskiy Aleksandr V
• Yin Mao
• Lowinger Timothy B
• Thomas Joshua D
• Stevenson Cheri A
• Gurijala Venu R

Classifications

• A61K47/6883 Primary

  Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy · CPC title

• A61K47/6853

  Carcino-embryonic antigens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C08L71/00

  Compositions of polyethers obtained by reactions forming an ether link in the main chain (of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06); Compositions of derivatives of such polymers · CPC title

• C08G65/3322

  acyclic · CPC title