Neutrokine-alpha fusion proteins

• US 8,212,004 B2
• Filed: 02/10/2005
• Issued: 07/03/2012
• Est. Priority Date: 03/02/1999
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Yu, Guo-Liang, Ebner, Reinhard, Ni, Jian
• Primary Examiner(s): Bunner, Bridget E
• Application Number:
  US11/054,539
• Publication Number:
  US 20050186637A1
• Time in Patent Office: 2,700 Days
• Field of Search: None
• US Class Current: 530/350
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• 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 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/52 Assays involving cytokines
• CPC Class Codes: G01N 2800/24 : Immunology or allergic disorders
• CPC Class Codes: G01N 33/564 : for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/56972 : White blood cells

Abstract

The present invention relates to nucleic acid molecules encoding Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to antibodies or portions thereof that specifically bind Neutrokine-alpha and/or Neutrokine-alphaSV and diagnostic and therapeutic methods using these antibodies. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders using the compositions of the invention.

Claims

1. An isolated protein comprising a Neutrokine-alpha protein fused to a toxin protein, wherein said Neutrokine-alpha protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of amino acid residues 134-285 of SEQ ID NO;

2; and

(b) an amino acid sequence that is at least 90% identical to amino acid residues 134-285 of SEQ ID NO;

2.

2. The protein of claim 1, wherein said toxin protein is selected from the group consisting of:

(a) a ribosome inactivating protein;

(b) a cytotoxin; and

(c) a cytotoxic prodrug.

3. The protein of claim 1, wherein said toxin protein is thymidine kinase, endonuclease, RNAse, alpha toxin, ricin, abrin, Pseudomonas exotoxin A, diphtheria toxin, saporin, momordin, gelonin, pokeweed antiviral protein, alpha-sarcin, or cholera toxin.

4. A composition comprising the isolated protein of claim 1 and a carrier.

5. A kit comprising the composition of claim 4.

6. An isolated protein comprising a Neutrokine-alpha protein fused to a toxin protein, wherein said Neutrokine-alpha protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of amino acid residues 134-285 of SEQ ID NO;

2; and

(b) an amino acid sequence that is at least 90% identical to amino acid residues 134-285 of SEQ ID NO;

2;

and wherein said toxin protein comprises an amino acid sequence selected from the group consisting of;

(i) a polypeptide comprising the full-length gelonin polypeptide;

(ii) a polypeptide comprising amino acids 47 to 297 of the full-length gelonin polypeptide; and

(iii) a polypeptide comprising amino acids 47 to 297 of the full-length gelonin polypeptide wherein Asp-297 is changed to Cys-297.

7. A composition comprising the isolated protein of claim 6 and a carrier.

8. A kit comprising the composition of claim 7.