Epidermal growth factor receptor targeted/immunomodulatory fusion proteins and methods of use for them

Patent metadata

Field	Value
Publication number	US-10385348-B2
Application number	US-201715795404-A
Country	US
Kind code	B2
Filing date	Oct 27, 2017
Priority date	Apr 30, 2012
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

Abstract

The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

First claim

That which is claimed is:

1. A method of reducing tumor Transforming growth factor-beta (TGF-β) levels, the method comprising contacting cancer cells with a therapeutic amount of a chimeric fusion protein, wherein the chimeric fusion protein comprises a targeting moiety to target a cancer cell and an immunomodulating moiety that counteracts immune tolerance, wherein the targeting moiety and the immunomodulating moiety are linked by an amino acid spacer of sufficient length of amino acid residues so that both moieties can successfully bind to their individual targets, wherein the immunomodulating moiety is TGF-βRII consisting of an amino acid sequence of SEQ ID NO: 4, wherein the amino acid spacer is selected from SEQ ID NO: 3 or SEQ ID NO: 11; and wherein the targeting moiety is an Anti-EGFR1 antibody consisting of heavy chain of SEQ ID NO: 5 and light chain of SEQ ID NO: 6; wherein SEQ ID NO: 4 is attached via the amino acid spacer to the C-terminus of SEQ ID NO: 6.

2. The method of claim 1 , wherein the cancer cells are in a subject in need of treatment.

3. The method of claim 1 , further comprising administering the chimeric fusion protein in combination with another existing cancer treatment.

4. The method of claim 1 , wherein suppression of an immune system of the subject in the cancer cell is reduced.

5. The method of claim 1 , wherein cytotoxic lymphocytes and Natural Killer cells are activated in the subject.

6. The method of claim 1 , wherein lysis of cancer cells is increased.

7. The method of claim 1 , wherein SEQ ID NO: 4 binds to TGF-β.

8. The method of claim 1 , wherein the Anti-EGFR1 antibody binds to a cancerous tumor cell.

Assignees

• Biocon Ltd

Inventors

• Govindappa Nagaraj
• Sastry Kedarnath
• Soares Maria Melina

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/02

  containing a signal sequence · CPC title

• A61K38/00

  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 title

• C07K14/70532

  B7 molecules, e.g. CD80, CD86 · CPC title