Hybrid immunoglobulins

• US 5,116,964 A
• Filed: 11/22/1989
• Issued: 05/26/1992
• Est. Priority Date: 02/23/1989
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Capon, Daniel J., Lasky, Laurence A.
• Primary Examiner(s): Lacey, David L.
• Assistant Examiner(s): Ulm, John D.
• Application Number:
  US07/440,625
• Time in Patent Office: 916 Days
• Field of Search: 435/69.7, 435/172.3, 435/252.3, 435/320, 436/512, 530/350, 530/387, 536/27
• US Class Current: 536/23.5
• 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 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70514 CD4
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/04 containing an ER retention signal such as a C-terminal HDEL motif
• 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
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/705 containing a protein-A fusion
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins

Abstract

Immunoglobulin fusion polypeptides are provided, together with methods for making and using them, and nucleic acids encoding them. These polypeptides are useful as cell surface adhesion molecules and ligands, and are useful in therapeutic or diagnostic compositions and methods.

Claims

1. Nucleic acid encoding a polypeptide fusion comprising a ligand binding partner protein containing more than one polypeptide chain, wherein the ligand binding partner protein is not a platelet growth factor receptor or an insulin receptor, one of said chains being fused to an immunoglobulin constant region through C- or N-terminal amino or carboxyl groups.

2. Nucleic acid encoding a polypeptide fusion of a ligand binding partner protein and an immunoglobulin chain, wherein the ligand binding partner protein is not a platelet growth factor receptor or an insulin receptor, said ligand binding partner protein and said immunoglobulin chain being fused through C- or N-terminal amino or carboxyl groups, and said fusion further comprising an additional fusion of an agent selected from the group consisting of a multiple subunit (chain) polypeptide, a portion of an immunoglobulin superfamily member, a toxin and a polypeptide therapeutic agent not otherwise associated with an immunoglobulin, and an immunoglobulin chain.

3. The nucleic acid of claim 2 wherein said ligand binding partner is LHR and said agent in said additional fusion is CD4.

4. Nucleic acid encoding a polypeptide fusion comprising a ligand binding partner protein which comprises a LHR and an immunoglobulin chain, in which the ligand binding partner protein and immunoglobulin are fused through C- or N-terminal amino or carboxyl groups.

5. The nucleic acid of claim 4 wherein said immunoglobulin chain is obtained from IgG1, IgG2, IgG3, IgG4, IgE, IgD or IgM.

6. The nucleic acid of claim 4 wherein in said LHR the transmembrane and the cytoplasmic domains have been deleted.

7. The nucleic acid of claim 6 wherein the transmembrane and cytoplasmic domain deleted LHR is fused at its C-terminus to the N-terminus of an human IgG immunoglobulin heavy chain constant region sequence.

8. The nucleic acid of claim 7 wherein the transmembrane and cytoplasmic domain deleted LHR is fused at its C-terminus to the N-terminus of an IgG immunoglobulin sequence beginning in the hinge region just upstream of the papain cleavage site at residue 216, taking the first residue of the heavy chain constant region to be 114.