Patent EP0414178A2 successfully refreshed from Google Patents.
EP0414178A2
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EP
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Non-human primate CD4 polypeptides and human CD4 molecules capable of being glycosylated
Assignee: General Hospital Corp
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Filing: 1990-08-18
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Granted: —
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Expires: 2010-08-18
Abstract
Abstract The invention relates to substantially pure non-human primate CD4, and fragments thereof which bind to HIV or SIV gp120. The invention also relates to gp120 binding molecules related to human CD4 but which may exist in glycosylated form. The invention also relates to fusion proteins which comprise the CD4 molecules of the invention, or fragments thereof, and an immunoglobulin light or heavy chain, wherein the variable region of the light or heavy chain has been replaced with CD4 or fragment thereof which is capable of binding to gp120. The invention also relates to fusion proteins comprising the CD4 molecules of the invention and a cytotoxic polypeptide. The invention also relates to an immunoglobulin-like molecules comprising the fusion proteins of the invention together with an immunoglobulin light or heavy chain. The invention also relates to methods of treating HIV or SIV infection comprising administering the CD4 molecules of the invention, glycoproteins, fragments thereof, fusion proteins or immunoglobulin-like molecules of the invention to an animal. The invention also relates to assays for HIV or SIV comprising contacting a sample suspected of containing HIV or SIV gp120 with the CD4 molecules of the invention, fragments thereof, glycoproteins, immunoglobulin-like molecules, or fusion proteins of the invention, and detecting whether a complex is formed. The invention also relates to nucleic acid molecules which specify the proteins, glycoproteins and fusion proteins of the invention as weil as vectors and transformed hosts.
Inventors
- 👤 Brian Seed
- 👤 David Camerini
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-27 17:14
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/705; C07K14/70503; C07K14/70514; A; A61; A61P; A61P31/00; A61P31/12; C07K16/00; A61K; A61K38/00; C07K2319/00; C07K2319/01; C07K2319/02; C07K2319/33
Claims Analysis
Total Claims: 44
Claim 1
Independent Claim
22 words
A nucleic acid molecule specifying non-human primate CD4, or an HIV gp120 binding fragment thereof, which preferably is soluble in aqueous solution.
Claim 2
Dependent Claim
22 words
A nucleic acid molecule specifying non-human primate CD4, or an HIV gp120 binding fragment thereof, which preferably is soluble in aqueous solution.
Claim 3
Dependent Claim
22 words
The nucleic acid molecule of claim 1 which is DNA, RNA or is complementary to the nucleic acid molecule of claim 1.
Claim 4
Dependent Claim
11 words
The nucleic acid molecule of claim 1 which is detectably labeled.
Claim 5
Dependent Claim
97 words
The nucleic acid molecule of claim 1, wherein said non-human primate is the rhesus monkey and said molecule comprises the following DNA sequence: or a degenerate variant thereof, or wherein said non-human primate is the rhesus monkey and the said nucleic acid fragment comprises the following DNA sequence: or a degenerate variant thereof, or wherein said non-human primate is the chimpanzee and said molecule comprises the following DNA sequence: or a degenerate variant thereof, or wherein said non-human primate is the chimpanzee and said nucleic acid fragment comprises the following DNA sequence: or a degenerate variant thereof.
Claim 6
Dependent Claim
30 words
A recombinant DNA molecule comprising the following sequence: wherein Y is C or T, M is A or C, and S is C or G; or a degenerate variant thereof.
Claim 7
Dependent Claim
30 words
A recombinant DNA molecule comprising the following sequence: wherein Y is C or T, M is A or C, and S is C or G; or a degenerate variant thereof.
Claim 8
Dependent Claim
52 words
A nucleic acid molecule specifying glycosylated human CD4 with the cytoplasmic domain, comprising the following DNA sequence: wherein Y is C or T, and M is A or C; or a degenerate variant thereof; with the proviso that both Y is not T and M is not C at the same time.
Claim 9
Dependent Claim
52 words
A nucleic acid molecule specifying glycosylated human CD4 with the cytoplasmic domain, comprising the following DNA sequence: wherein Y is C or T, and M is A or C; or a degenerate variant thereof; with the proviso that both Y is not T and M is not C at the same time.
Claim 10
Dependent Claim
50 words
A nucleic acid molecule specifying a glycosylated human CD4 fragment, comprising the following DNA sequence: wherein Y is C or T, and M is A or C; or a degenerate variant thereof; with the proviso that both Y is not T and M is not C at the same time.
Claim 11
Dependent Claim
50 words
A nucleic acid molecule specifying a glycosylated human CD4 fragment, comprising the following DNA sequence: wherein Y is C or T, and M is A or C; or a degenerate variant thereof; with the proviso that both Y is not T and M is not C at the same time.
Claim 12
Dependent Claim
63 words
A nucleic acid molecule specifying a fusion protein, comprising: 1) the nucleic acid molecule of claim 1, linked to 2) a nucleic acid molecule specifying an immunoglobulin heavy chain, preferably of the class IgM, IgG1 or IgG3, wherein the nucleic acid sequence which specifies the variable region of said immunoglobulin heavy chain has been replaced with said nucleic acid molecule specifying said fragment.
Claim 13
Dependent Claim
73 words
A nucleic acid molecule specifying a fusion protein, comprising: 1) a nucleic acid molecule specifying a non-human primate CD4, or HIV or SIV gp120 binding fragment thereof, linked to 2) a nucleic acid molecule specifying an immunoglobulin light chain, preferably of the class IgM, IgG1 or IgG3, wherein the nucleic acid sequence which specifies the variable region of said immunoglobulin light chain has been replaced with said nucleic acid molecule specifying said fragment.
Claim 14
Dependent Claim
73 words
A nucleic acid molecule specifying a fusion protein, comprising: 1) a nucleic acid molecule specifying a non-human primate CD4, or HIV or SIV gp120 binding fragment thereof, linked to 2) a nucleic acid molecule specifying an immunoglobulin light chain, preferably of the class IgM, IgG1 or IgG3, wherein the nucleic acid sequence which specifies the variable region of said immunoglobulin light chain has been replaced with said nucleic acid molecule specifying said fragment.
Claim 15
Dependent Claim
38 words
A nucleic acid molecule specifying a fusion protein, comprising: 1) a nucleic acid molecule specifying a non-human primate CD4, or HIV or SIV gp120 binding fragment thereof, linked to 2) a nucleic acid molecule specifying a cytotoxic polypeptide.
Claim 16
Dependent Claim
38 words
A nucleic acid molecule specifying a fusion protein, comprising: 1) a nucleic acid molecule specifying a non-human primate CD4, or HIV or SIV gp120 binding fragment thereof, linked to 2) a nucleic acid molecule specifying a cytotoxic polypeptide.
Claim 17
Dependent Claim
17 words
A vector comprising the nucleic acid molecule of any one of claims 1 or 4 to 10.
Claim 18
Dependent Claim
113 words
A host transformed with the vector of claim 11, especially a host transformed with a vector comprising the nucleic acid molecule of claim 8, wherein said host expresses an immunoglobulin light chain together with the expression product of nucleic acid molecule to give an immunoglobulin-like molecule which binds to HIV or SIV gp120, or a host transformed with a vector comprising the nucleic acid molecule of claim 9, wherein said host expresses an immunoglobulin heavy chain together with the expression product of nucleic acid molecule to give an immunoglobulin-like molecule which binds to HIV or SIV gp120, and wherein said immunoglobulin heavy chain is preferably of the immunoglobulin class IgM, IgG1 or IgG3.
Claim 19
Dependent Claim
71 words
A method of producing non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, which comprises cultivating in a nutrient medium under protein-producing conditions, a host strain transformed with a vector comprising the nucleic acid molecule of claim 1, said vector further comprising expression signals which are recognized by said host strain and direct expression of said non-human primate CD4, and recovering the non-human primate CD4 so produced.
Claim 20
Dependent Claim
142 words
A method of producing a fusion protein comprising non-human primate CD4, or fragment thereof which binds to gp120, and an immunoglobulin heavy chain, wherein the variable region of the immunoglobulin chain has been substituted with non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, which comprises cultivating in a nutrient medium under protein-producing conditions, a host strain transformed with a vector comprising the nucleic acid molecule of claim 8, said vector further comprising expression signals which are recognized by said host strain and direct expression of said fusion protein, and recovering the fusion protein so produced, and wherein said host strain preferably is a myeloma cell line which produces immunoglobulin light chains and said fusion protein comprises an immunoglobulin heavy chain of the class IgM, igG1 or IgG3, wherein an immunoglobulin-like molecule comprising said fusion protein is produced.
Claim 21
Dependent Claim
136 words
A method of producing a fusion protein comprising non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, and an immunoglobulin light chain, wherein the variable region of theim- munoglobulin chain has been substituted with non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, which comprises: cultivating in a nutrient medium under protein-producing conditions, a host strain transformed with a vector comprising the nucleic acid molecule of claim 9, said vector further comprising expression signals which are recognized by said host strain and direct expression of said fusion protein, and recovering the fusion protein so produced, and wherein said host preferably produces immunoglobulin heavy chains of the class IgM, IgG1 and IgG3 together with said fusion protein to give an immunoglobulin-like molecule which binds to HIV or SIV gp120.
Claim 22
Dependent Claim
123 words
Substantially pure non-human primate CD4, especially a substantially pure non-human primate CD4, wherein said non-human primate is the rhesus monkey, comprising the following amino acid sequence: or a substantially pure non-human CD4, wherein said non-human primate is the chimpanzee, comprising the following amino acid sequence. or the glycosylated derivative thereof, or a substantially pure non-human CD4 comprising the following amino acid sequence: wherein -@- is Thr or lie, -#- is Val or Ala, -$- is Thr or Pro, and -%- is Gln or Glu; or the glycosylated derivative thereof, or a substantially pure non-human CD4 comprising the following amino acid sequence: wherein -@- is Thr or lie, -#- is Val or Ala, and -$- is Thr or Pro; or the glycosylated derivative thereof.
Claim 23
Dependent Claim
123 words
Substantially pure non-human primate CD4, especially a substantially pure non-human primate CD4, wherein said non-human primate is the rhesus monkey, comprising the following amino acid sequence: or a substantially pure non-human CD4, wherein said non-human primate is the chimpanzee, comprising the following amino acid sequence. or the glycosylated derivative thereof, or a substantially pure non-human CD4 comprising the following amino acid sequence: wherein -@- is Thr or lie, -#- is Val or Ala, -$- is Thr or Pro, and -%- is Gln or Glu; or the glycosylated derivative thereof, or a substantially pure non-human CD4 comprising the following amino acid sequence: wherein -@- is Thr or lie, -#- is Val or Ala, and -$- is Thr or Pro; or the glycosylated derivative thereof.
Claim 24
Dependent Claim
95 words
A gp120 binding molecule comprising the following amino acid sequence: wherein -@- is Thr or lie, and -$- is Thr or Pro; or the glycosylated derivative thereof; with the proviso that at least one of -@- and -$- is Thr, or comprising the following amino acid sequence: wherein -@- is Thr or Ile, and -$- is Thr or Pro; or the glycosylated derivative thereof; with the proviso that at least one of -@- and -$- is Thr, and wherein the gp120 binding molecule is preferably linked to a cytotoxic polypeptide, radiolabeled or NMR imaging agent.
Claim 25
Dependent Claim
95 words
A gp120 binding molecule comprising the following amino acid sequence: wherein -@- is Thr or lie, and -$- is Thr or Pro; or the glycosylated derivative thereof; with the proviso that at least one of -@- and -$- is Thr, or comprising the following amino acid sequence: wherein -@- is Thr or Ile, and -$- is Thr or Pro; or the glycosylated derivative thereof; with the proviso that at least one of -@- and -$- is Thr, and wherein the gp120 binding molecule is preferably linked to a cytotoxic polypeptide, radiolabeled or NMR imaging agent.
Claim 26
Dependent Claim
28 words
A non-human primate, preferably rhesus monkey or the chimpanzee, CD4 fragment which is capable of binding to HIV or SIV gp120, which preferably is soluble in aqueous solution.
Claim 27
Dependent Claim
28 words
A non-human primate, preferably rhesus monkey or the chimpanzee, CD4 fragment which is capable of binding to HIV or SIV gp120, which preferably is soluble in aqueous solution.
Claim 28
Dependent Claim
41 words
The non-human primate CD4 fragment of claim 18, wherein said non-human primate is the rhesus monkey, comprising the following amino acid sequence: or wherein said non-human primate is the chimpanzee, comprising the following amino acid sequence: or the glycosylated derivative thereof.
Claim 29
Dependent Claim
84 words
A fusion protein comprising non-human primate CD4, or fragment thereof which is capable of binding to HIV or SIV gp120, fused at the C-terminus to a second protein which comprises an immunoglobulin heavy chain of the class IgM, IgG1 or IgG3, wherein the variable region of said heavy chain immunoglobulin has been replaced with CD4, or HIV gp120-binding fragment thereof, which fusion protein preferably is detectably labeled, or linked to a cytotoxic polypeptide, preferably comprising ricin or diphtheria toxin, radiolabel or NMR imaging agent.
Claim 30
Dependent Claim
84 words
A fusion protein comprising non-human primate CD4, or fragment thereof which is capable of binding to HIV or SIV gp120, fused at the C-terminus to a second protein which comprises an immunoglobulin heavy chain of the class IgM, IgG1 or IgG3, wherein the variable region of said heavy chain immunoglobulin has been replaced with CD4, or HIV gp120-binding fragment thereof, which fusion protein preferably is detectably labeled, or linked to a cytotoxic polypeptide, preferably comprising ricin or diphtheria toxin, radiolabel or NMR imaging agent.
Claim 31
Dependent Claim
59 words
A fusion protein comprising non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, fused at the terminus to a second protein comprising an immunoglobulin light chain wherein the variable region has been deleted, which preferably is detectably labeled or linked to a cytotoxic polypeptide, especially comprising ricin or diphtheria toxin, radiolabel or NMR imaging agent.
Claim 32
Dependent Claim
59 words
A fusion protein comprising non-human primate CD4, or fragment thereof which binds to HIV or SIV gp120, fused at the terminus to a second protein comprising an immunoglobulin light chain wherein the variable region has been deleted, which preferably is detectably labeled or linked to a cytotoxic polypeptide, especially comprising ricin or diphtheria toxin, radiolabel or NMR imaging agent.
Claim 33
Dependent Claim
39 words
The fusion protein of claim 19 or 20, wherein said CD4 fragment is derived from the rhesus monkey, comprising the following amino acid sequence: wherein said CD4 fragment is derived from the chimpanzee, comprising the following amino acid sequence:
Claim 34
Dependent Claim
33 words
An immunoglobulin-like molecule, comprising the fusion protein of claim 19 and an immunoglobulin light chain, which immunoglobulin-like molecule preferably is detectably labelled or linked to a cytotoxic polypeptide, radiolabel or NMR imaging agent.
Claim 35
Dependent Claim
45 words
An immunoglobulin-like molecule comprising the fusion protein of claim 21 and an immunoglobulin heavy chain of the class IgM, IgG1 or IgG3, which immunoglobulin-like molecule preferably is detectably labeled or wherein said fusion protein is linked to a cytotoxic polypeptide, radiolabel or NMR imaging agent.
Claim 36
Dependent Claim
24 words
A non-human primate CD4 molecule, or an HIV or SIV gp120 binding fragment thereof, linked to a cytotoxic polypeptide, radiolabel or NMR imaging agent.
Claim 37
Dependent Claim
24 words
A non-human primate CD4 molecule, or an HIV or SIV gp120 binding fragment thereof, linked to a cytotoxic polypeptide, radiolabel or NMR imaging agent.
Claim 38
Dependent Claim
55 words
A complex, comprising a) HIV or SIV gp120 and b) substantially pure non-human primate CD4, or an HIV or SIV gp120 binding non-human primate CD4 fragment, or an HIV or SIV gp120 binding non-human primate CD4 soluble fragment, or the fusion protein of claim 20 or 21, or the gp120 binding molecule of claim 17.
Claim 39
Dependent Claim
32 words
The complex of claim 26, wherein said gp120 is a part of an HIV or SIV, is expressed on the surface of an HIV or SIV-infected cell or is present in solution.
Claim 40
Dependent Claim
42 words
A method for the detection of HIV or SIV gp120 in a sample, comprising (a) contacting a sample suspected of containing HIV or SIV gp120 with the fusion protein of claim 20 or 21, and (b) detecting whether a complex is formed.
Claim 41
Independent Claim
62 words
A method for the detection of HIV or SIV gp120 in a sample, comprising (a) contacting a sample suspected of containing HIV or SIV gp120 with non-human primate CD4, or fragment thereof which is capable of binding to HIV or SIV gp120, and wherein preferably said non-human primate CD4 or fragment thereof is detectably labeled, (b) detecting whether a complex has formed.
Claim 42
Independent Claim
62 words
A method for the detection of HIV or SIV gp120 in a sample, comprising (a) contacting a sample suspected of containing HIV or SIV gp120 with non-human primate CD4, or fragment thereof which is capable of binding to HIV or SIV gp120, and wherein preferably said non-human primate CD4 or fragment thereof is detectably labeled, (b) detecting whether a complex has formed.
Claim 43
Dependent Claim
46 words
A method for the detection of HIV or SIV gp120 in a sample, comprising (a) contacting a sample suspected of containing HIV or SIV gp120 with the gp120 binding molecule of claim 17, which preferably is detectably labeled; and (b) detecting whether a complex has formed.
Claim 44
Dependent Claim
59 words
A pharmaceutical composition comprising a therapeutically effective amount of substantially pure non-human primate CD4 or a therapeutically effective amount of a non-human primate CD4 fragment which is capable of binding to HIV or SIV gp120, and preferably soluble in aqueous solution, or a therapeutically effective amount of the gp120 binding molecule of claim 17; and a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
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