Novel Chimeric Proteins and Methods for Using The Same

• US 20140227315A1
• Filed: 03/17/2014
• Published: 08/14/2014
• Est. Priority Date: 10/31/2002
• Status: Abandoned Application

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Tykocinski, Mark L., Huang, Jui Han
• Application Number:
  US14/215,436
• Publication Number:
  US 20140227315A1
• Time in Patent Office: Days
• US Class Current: 424/192.1
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Novel chimeric proteins are disclosed. The proteins comprise at least two portions. The first portion binds to a first cell and decreases the cell'"'"'s ability to send a trans signal to a second cell; the second portion sends its own trans signal to the second cell. Methods for making and using these proteins in the treatment of cancer, viral infections, autoimmune and alloimmune diseases are also disclosed, as are pharmaceutical formulations comprising the novel chimeric proteins and genes. Either the proteins themselves or a genetic sequence encoding the protein can be administered. Other methods are also disclosed in which two molecular components result in decrement of a first trans signal from a first cell and the conferring of a second trans signal to a second cell.

Claims

1-33. -33. (canceled)

34. A method of treating a subject having cancer, the method comprising administering a chimeric protein to the subject, wherein the chimeric protein comprises:

a first protein that binds to at least one surface molecule on a first cell and results in the decrement of a first trans signal from said cell; and

a second protein that binds to at least one surface molecule on a second cell and sends a second trans signal to said second cell, wherein the first and second trans signals sent from the surface of said first and second cells are not the same, and wherein when the first protein is selected from the group consisting of CTLA-4, CD27, CD40, and ICOS and second protein is selected from the group consisting of FasL, TRAIL, TWEAK, CAR, CD8, PP14, BAFF/TALL-1/THANK/BLys, PD-1 and RCAS1.

35. The method of claim 34, wherein said cancer is selected from the group consisting of ovarian carcinoma, breast carcinoma, gastrointestinal cancer, a malignant glioma, prostate carcinoma and leukemia.

36. The method of claim 35, wherein said gastrointestinal cancer comprises colon carcinoma.

37. The method of claim 35, wherein said malignant glioma comprises glioblastoma multiforme.

38. The method of claim 35, wherein said leukemia is selected from the group consisting of myelomonocytic leukemia and chronic myeloid leukemia.

39. The method of claim 34, wherein said first protein is CTLA-4 and said second protein is FasL.

40. The method of claim 34, wherein said administering said chimeric protein comprises administering a pharmaceutical formulation comprising the chimeric protein in a suitable pharmaceutical carrier, wherein said pharmaceutical formulation is administered in unit dosage form to a subject in need thereof in therapeutically effective amounts.