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1. WO2006093794 - HETERODIMERIC PROTEIN BINDING COMPOSITIONS

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[ EN ]
CLAIMS
WHAT IS CLAIMED IS:
1. A heterodimeric protein binding composition comprising a modified immunoglobulin molecule having a heavy and light chain, wherein one or more light chain domains are substituted for one or more heavy chain domains on the immunoglobulin heavy chain, and/or one or more heavy chain domains are substituted for one or more light chain domains on the immunoglobulin light chain of the immunoglobulin molecule.
2. The modified immunoglobulin molecule of claim 1, wherein the V L-C L light chain domains are substituted for the V H-C HI regions of the immunoglobulin heavy chain and the VH-C HI domains of the heavy chain are substituted for the V L-C L light chain regions of the immunoglobulin light chain.
3. The modified immunoglobulin molecule of Claim 1, wherein the immunoglobulin molecule is IgGl.
4. The modified immunoglobulin molecule of claim 1 further comprising an antigen-binding region.
5. The modified immunoglobulin molecule of claim 1, wherein the immunoglobulin molecule is an IgA, IgG, IgM, IgE, or IgD molecule.
6. A polynucleotide that encodes a modified immunoglobulin molecule of claim 1.
7. A vector comprising the polynucleotide of claim 6.
8. A host cell transfected with the vector of claim 8.
9. A method of producing a modified immunoglobulin molecule comprising culturing the host cell of claim 8 and recovering the modified immunoglobulin molecule so produced.

10. The method of claim 9, wherein the cell is a eucaryotic or procaryotic cell.
11. The method of claim 10, wherein the cell is a mammalian, avian, reptilian, insect, plant, bacterial, fungal or yeast cell.

12. The method of claim 11, wherein the mammalian cell is a human, rabbit, murine, rat, hamster or bovine cell.
13. The method of claim 12, wherein the host cell is at least one selected from COS-I, COS-7, HEK 293, BHK21, CHO, BSC-I, HepG2, 653, SP2/0, NS/O, HeLa, other myeloma cells or lymphoma cells, or any derivative, immortalized or transformed cell thereof.
14. A pharmaceutical composition comprising the modified immunoglobulin molecule of claim 1 and a pharmaceutically acceptable carrier.
15. A method of treating or protecting against an infection in a subject comprising administering the composition of claim 14 to the subject.
16. A nucleic acid composition, comprising an isolated nucleic acid according to claim 6 and a carrier or diluent.
17. An antibody vector according to claim 7, wherein said vector comprises at least one promoter selected from the group consisting of a late or early SV490 promoter, a CMV promoter, an HSV tk promoter, a pgk (phosphoglycerate kinase) promoter, a human immunoglobulin promoter or an EF-I alpha promoter.
18. An antibody vector according to claim 7, wherein said vector comprises at least one selection gene or portion thereof selected from at least one of methotrexate (MTX), green fluorescent protein (GFP), dihydrofolate reductase (DHFR), neomycin (G418), or glutamine synthetase (GS).
19. A method for producing a modified immunoglobulin of claim 1 comprising translating a nucleic acid according to claim 6 or an endogenous nucleic acid that hybridizes thereto under stringent conditions, under conditions in vitro, in vivo or situ, such that the modified immunoglobulin is expressed in detectable or recoverable amounts.
20. A method for modulating at least one disorder or condition in a cell, tissue, organ or animal, comprising contacting or administering a disorder or condition modulating effective amount of at least one modified immunoglobulin according to claim 1 with, or to, said cell, tissue, organ or animal.

21. A method according to claim 20 wherein said effective amount is 0.01-100 mg/kilogram of said cells, tissue, organ or animal.
22. A method according to any of claims 20-21 , wherein said contacting or said administrating is by at least one mode selected from intravenous, intramuscular, colus, subcutaneous, respiratory, inhalation, vaginal, rectal, buccal, sublingual, intranasal, or transdermal.
23. A formulation comprising at least one modified immunoglobulin according to claim 1, and at least one selected from sterile water, sterile buffered water, or at least one
preservative selected from the group consisting of phenol, m-cresol, p-cresol, o-cresol, chlorocresol, benzyl alcohol, phenylmercuric nitrite, phenoxyethanol, formaldehyde, chlorobutanol, magnesium chloride, alkylparaben, benzalkonium chloride, benzethonium chloride, sodium dehydroacetate and thimerosal, ormixtures thereof, in an aqueous diluent.

24. A formulation of Claim 23, wherein the concentration of modified immunoglobulin is about 0.1 mg/ml to about 100 mg/ml.
25. A formulation of Claim 24, further comprising an isotonicity agent.
26. A formulation of Claim 25, further comprising a physiologically acceptable buffer.

27. A formulation comprising at least one modified immunoglobulin according to Claim 1 in lyophilized form in a first container, and an optional second container comprising sterile water, sterile buffered water, or at least one preservative selected from the group consisting of phenol, m-cresol, p-cresol, o-cresol, chlorocresol, benzyl alcohol, phenylmercuric nitrite, phenoxyethanol, formaldehyde, chlorobutanol, magnesium chloride, alkylparaben, benzalkonium chloride, benzethonium chloride, sodium dehydroacetate and thimerosal, or mixtures thereof in an aqueous diluent.
28. A method of treating a disease or condition in a patient, comprising administering to a patient in need thereof a formulation according to Claim 24.
29. A method for producing at least one modified immunoglobulin according to claim 1, comprising providing a host cell or transgenic animal or transgenic plant or plant cell capable of expressing in recoverable amounts said antibody or specified portion or variant.

30. A method according to claim 29, wherein said host cell is a mammalian cell, a plant cell or a yeast cell.
31. A method according to claim 30, wherein said transgenic animal is a mammal.
32. A method according to claim 33, wherein said transgenic mammal is selected from a goat, a cow, a sheep, a horse, and a non-human primate.
33. A transgenic animal or plant expressing at least one antibody according to claim 1.

34. At least one modified immunoglobulin produced by a method according to claim 29.

35. A method of modifying the ability of an immunoglobulin molecule having FcR-binding and Clq-binding domains to recruit effector functions such as ADCC, FcR-mediated phagocytosis, and complement lysis, which method comprises substituting one or more light chain domains for one or more heavy chain domains on the immunoglobulin heavy chain, and/or substituting one or more heavy chain domains for one or more light chain domains on the immunoglobulin light chain of the immunoglobulin molecule thereby reorienting the relative position of the FcR-binding and Clq-binding domains relative to the antigen-binding domain of the immunoglobulin molecule.