Protein-polymer-drug conjugates

Patent metadata

Field	Value
Publication number	US-10316080-B2
Application number	US-201414512275-A
Country	US
Kind code	B2
Filing date	Oct 10, 2014
Priority date	Oct 11, 2013
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

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 12:1 to about 18:1.

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 disorder 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 disorder is a cancer 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

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/18 Primary

  against material from animals or humans · CPC title

• C08G65/3322

  acyclic · CPC title

• A61K47/59 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K47/6843

  the antibody targeting a material from animals or humans · CPC title