Antibodies that bind the cytokine designated LERK-5

• US 20020103358A1
• Filed: 10/15/2001
• Published: 08/01/2002
• Est. Priority Date: 07/08/1994
• Status: Active Grant

• Current Assignee: Immunex Corporation (Amgen Inc.)
• Original Assignee: Immunex Corporation (Amgen Inc.)
• Inventors: Cerretti, Douglas P., Reddy, Pranhitha
• Granted Patent: US 6,596,852 B2
• Time in Patent Office: Days
• US Class Current: 536/23.2
• 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: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• 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 2319/00 Fusion polypeptide

Abstract

LERK-5 polypeptides are disclosed, along with DNA sequences, vectors and transformed host cells useful in producing LERK-5. The LERK-5 polypeptides bind to elk and to hek, which are members of the eph/elk family of receptor tyrosine kinases.

Claims

1. An isolated DNA that encodes a LERK-5 protein capable of binding elk and hek, wherein said LERK-5 comprises an amino acid sequence selected from the group consisting of amino acids -25 to 308 of SEQ ID NO:

2 and 1-308 of SEQ ID NO;

2.

2. A DNA according to claim 1, wherein said DNA comprises a nucleotide sequence selected from the group consisting of nucleotides 1 to 1002 of SEQ ID NO:

1 and nucleotides 76 to 1002 of SEQ ID NO;

1.

7. An expression vector comprising a DNA according to claim 1.

11. A process for preparing an LERK-5 polypeptide, comprising culturing a host cell transformed with a vector according to claim 7 under conditions promoting expression of LERK-5, and recovering the LERK-5 polypeptide from the culture.

16. Purified LERK-5 according to claim 15, wherein said LERK-5 comprises an amino acid sequence selected from the group consisting of amino acids 1-308 of SEQ ID NO:

2 and 1-199 of SEQ ID NO;

2.

19. An antibody that is immunoreactive with a human LERK-5 polypeptide according to claim 16.

20. An antibody according to claim 19, wherein said antibody is a monoclonal antibody.

3. An isolated DNA encoding a soluble human LERK-5 protein capable of binding elk and hek, wherein said LERK-5 comprises an amino acid sequence selected from the group consisting of amino acids -24 to 199 of SEQ ID NO:

2 and 1-199 of SEQ ID NO;

2.

4. A DNA according to claim 3, wherein said DNA comprises a nucleotide sequence selected from the group consisting of nucleotides 1 to 672 of SEQ ID NO:

1 and nucleotides 76 to 672 of SEQ ID NO;

1.

8. An expression vector comprising a DNA according to claim 3.

12. A process for preparing an LERK-5 polypeptide, comprising culturing a host cell transformed with a vector according to claim 8 under conditions promoting expression of LERK-5 and recovering the LERK-5 polypeptide from the culture.

5. An isolated DNA that encodes a LERK-5 polypeptide capable of binding elk or hek, wherein said LERK-5 polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of residues -25 to 199 of SEQ ID NO:

2 and 1-199 of SEQ ID NO;

2.

9. An expression vector comprising a DNA according to claim 5.

13. A process for preparing an LERK-5 polypeptide, comprising culturing a host cell transformed with a vector according to claim 9 under conditions promoting expression of LERK-5, and recovering the LERK-5 polypeptide from the culture.

17. A purified LERK-5 polypeptide, wherein said polypeptide is encoded by a DNA according to claim 5.

6. An isolated DNA that encodes a LERK-5 polypeptide capable of binding elk and hek, wherein said LERK-5 polypeptide comprises an extracellular domain, a transmembrane region, and a cytoplasmic domain, and wherein said LERK-5 polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of residues -25 to 308 of SEQ ID NO:

2 and 1-308 of SEQ ID NO;

2.

10. An expression vector comprising a DNA according to claim 6.

14. A process for preparing an LERK-5 polypeptide, comprising culturing a host cell transformed with a vector according to claim 10 under conditions promoting expression of LERK-5, and recovering the LERK-5 polypeptide from the culture.

18. A purified LERK-5 polypeptide, wherein said polypeptide is encoded by a DNA according to claim 6.

15. A purified mature human LERK-5 protein capable of binding elk and hek, wherein said human LERK-5 protein is characterized by the N-terminal amino acid sequence Lys-Ser-Ile-Val-Leu-Glu-Pro-Ile-Tyr-Trp-Asn-Ser-.

21. A fusion protein comprising a soluble human LERK-5 polypeptide comprising amino acids 1-199 of SEQ ID NO:

2, fused to the N-terminus of an Fc polypeptide.

22. A dimer comprising two fusion proteins according to claim 21, wherein said proteins are joined by disulfide bonds.