Treatment of CD47+ disease cells with SIRP alpha-Fc fusions

• US 9,969,789 B2
• Filed: 12/17/2013
• Issued: 05/15/2018
• Est. Priority Date: 12/17/2012
• Status: Active Grant

• Current Assignee: Pfizer Inc.
• Original Assignee: Trillium Therapeutics Inc. (Pfizer Inc.)
• Inventors: Uger, Robert Adam, Slavova-Petrova, Penka Slavtcheva, Pang, Xinli
• Primary Examiner(s): Dent, Alana Harris
• Application Number:
  US14/653,165
• Publication Number:
  US 20150329616A1
• Time in Patent Office: 1,610 Days
• Field of Search: None
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRPα/CD47 axis. The agent is a human SIRPα fusion protein that displays negligible CD47 agonism and negligible red blood cell binding. The fusion protein comprises an IgV domain from variant 2 of human SIRPα, and an Fc having effector function. The IgV domain binds human CD47 with an affinity that is at least five fold greater than the affinity of the entire extracellular region of human SIRPα. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Claims

1. A human SIRPa fusion protein that inhibits the growth and/or proliferation of a CD47⁺ disease cell, wherein the SIRPα

fusion protein comprises SEQ ID No. 25.

2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of a fusion protein according to claim 1 effective to inhibit the growth or proliferation of a CD47⁺ disease cell.

3. A human SIRPa fusion protein that inhibits the growth and/or proliferation of a CD47⁺ disease cell, wherein the human SIRPa fusion protein consists of SEQ ID No. 25.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of a fusion protein according to claim 3 effective to inhibit the growth or proliferation of a CD47⁺ disease cell.