Patent EP0200090A2 successfully refreshed from Google Patents.
EP0200090A2
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EP
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Tissue-derived tumor growth inhibitors, methods of preparation and uses thereof
Assignee: OSI Pharmaceuticals LLC
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Filing: 1986-04-15
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Granted: —
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Expires: 2006-04-15
Abstract
Abstract An acidified, ethanol extract derived from human tissue which comprises a plurality of acidic polypeptides, each of which has a molecular weight less than about 20,000 daltons and each of which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line - (CCL64) while stimulating the growth of normal human foreskin fibroblasts is disclosed. The inhibitory activity against human tumor cell growth is not destroyed upon increasing the temperature of the acidified, ethanol extract to about 100°C for about 3 minutes or adding acetic acid until the acidified, ethanol extract is up to about 1.0 molar in acetic acid. Further, the activity of the acidified, ethanol extract is enhanced when the acidified, ethanol extract is prepared at about 4°C rather than about at 23°C. An acidified, ethanol extract derived from human umbilical cord which has been treated to removed substantially all blood, all extracellular soluble components and substantially all intracellular soluble components which comprises at least one acidic polypeptide having an apparent molecular weight less than about 30,000 daltons, compositions of matter designated tissue-derived growth inhibitor-1 (TGI-1), tissue-derived growth inhibitor (TGI), and tissue-derived growth inhibitor-2 (TGI-2) and a heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV, are also disclosed as are methods of preparation, pharmaceutical compositions which include, and uses of the foregoing.
Inventors
- 👤 Kenneth K. Iwata
- 👤 John R. Stephenson
- 👤 Leslie I. Gold
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-26 20:45
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/495; A; A61; A61P; A61P35/00; A61P43/00; A61K; A61K38/00
Claims Analysis
Total Claims: 69
Claim 1
Independent Claim
127 words
An acidified, ethanol extract derived from human tissue which comprises a plurality of acidic polypeptides, each of which has a molecular weight less than about 20,000 daltons and each of which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the inhibitory activity against human tumor cell growth not being destroyed upon increasing the temperature of the acidified, ethanol extract to about 100°C for about 3 minutes or upon adding acetic acid until the acidified, ethanol extract is up to about 1.0 molar in acetic acid and the inhibitory activity being enhanced when the acidified, ethanol extract is prepared at about 4°C rather than at about 23°C.
Claim 2
Dependent Claim
127 words
An acidified, ethanol extract derived from human tissue which comprises a plurality of acidic polypeptides, each of which has a molecular weight less than about 20,000 daltons and each of which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the inhibitory activity against human tumor cell growth not being destroyed upon increasing the temperature of the acidified, ethanol extract to about 100°C for about 3 minutes or upon adding acetic acid until the acidified, ethanol extract is up to about 1.0 molar in acetic acid and the inhibitory activity being enhanced when the acidified, ethanol extract is prepared at about 4°C rather than at about 23°C.
Claim 3
Dependent Claim
14 words
An acidified, ethanol extract of claim 1, wherein the human tissue is umbilical cord.
Claim 4
Dependent Claim
13 words
An acidified, ethanol extract of claim 1, wherein the human tissue is placenta.
Claim 5
Dependent Claim
124 words
An acidified, ethanol extract derived from human umbilical cord which has been treated to remove substantially all blood, all extracellular soluble components and substantially all intracellular soluble components which comprises at least one acidic polypeptide having an apparent molecular weight less than about 30,000 daltons under nonreducing conditions and having the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the inhibitory activity against human tumor cell growth not being destroyed upon increasing the temperature of the acidified, ethanol extract to about 100°C for about 3 minutes or upon adding acetic acid until the acidified, ethanol extract is up to about 1.0 molar in acetic acid.
Claim 6
Dependent Claim
124 words
An acidified, ethanol extract derived from human umbilical cord which has been treated to remove substantially all blood, all extracellular soluble components and substantially all intracellular soluble components which comprises at least one acidic polypeptide having an apparent molecular weight less than about 30,000 daltons under nonreducing conditions and having the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the inhibitory activity against human tumor cell growth not being destroyed upon increasing the temperature of the acidified, ethanol extract to about 100°C for about 3 minutes or upon adding acetic acid until the acidified, ethanol extract is up to about 1.0 molar in acetic acid.
Claim 7
Dependent Claim
210 words
A composition of matter designated tissue-derived growth inhibitor-1 (TGI-1) which comprises at least one polypeptide having the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) but not the growth of normal human foreskin fibroblasts and having an apparent molecular weight in the range from about 5,000-16,000 daltons, the composition a) being recoverable as a defined activity on high performance liquid chromatography of the acidified, ethanol extract of claim 1 with a linear gradient of acetonitrile containing 0.05% trifluroacetic acid at about 26-34% acetonitrile and being recoverable as a defined activity on high performance liquid chromatography of the acidified, ethanol extract of claim 1 with a linear gradient of 2-propanol containing 0.05% trifluoroacetic acid at about 17-23% 2-propanol, and b) being separable when eluted on high performance liquid chromatography with a linear gradient of 2-propanol containing 0.05% trifluroacetic acid into two activities, one of which elutes at about 26% 2-propanol and preferentially inhibits the growth of human tumor cells but not the growth of an established mink lung cell line - (CCL64) and the other of which elutes at about 23% 2-propanol and preferentially inhibits the growth of an established mink lung cell line - (CCL64) but not human tumor cells.
Claim 8
Dependent Claim
121 words
A composition of matter designated tissue-derived growth inhibitor (TGI) which comprises at least one polypeptide having the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) but not the growth of normal human foreskin fibroblasts and having an apparent molecular weight in the range from about 20,000-30,000 daltons, the composition a) being recoverable as a defined activity on high performance liquid chromatography of the acidified, ethanol extract of claim 4 with a linear gradient of acetonitrile containing 0.05% trifluroacetic acid at about 28-34% acetonitrile and b) being resolved as a single peak of defined activity from a cation exchange resin when eluted by a linear NaCI gradient at about 0.6-0.7% M NaCl.
Claim 9
Dependent Claim
126 words
A composition of matter designated tissue-derived growth inhibitor-2 (TGI-2) which comprises at least one polypeptide having the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) but not the growth of normal human foreskin fibroblasts and having an apparent molecular weight in the range from about 5,000-16,000 daltons, the composition being recoverable as a defined activity on high performance liquid chromatography of the acidified, ethanol extract of claim 1 with a linear gradient of acetonitrile containing 0.05% trifluroacetic acid at about 35-39% acetonitrile and being recoverable as a defined activity on high performance liquid chromatography of the acidified, ethanol extract of claim 1 with a linear gradient of 2-propanol containing 0.05% trifluoroacetic acid at about 23-27% 2-propanol.
Claim 10
Dependent Claim
74 words
A heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV, each of which has the property of inhibiting the growth of human tumor cells, all of which except CM-1 have the property of substantially inhibiting the growth of an established mink lung cell line (CCL64) and none of which inhibit the growth of normal human foreskin fibroblasts, the population being recoverable by cation exchange chromatography of the acidified, ethanol extract of claim 1.
Claim 11
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of the acidified, ethanol extract of claim 1 and a suitable pharmaceutical carrier.
Claim 12
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of the acidified, ethanol extract of claim 4 and a suitable pharmaceutical carrier.
Claim 13
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of the composition of matter of claim 5 and a suitable pharmaceutical carrier.
Claim 14
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of the composition of matter of claim 6 and a suitable pharmaceutical carrier.
Claim 15
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of the composition of matter of claim 7 and a suitable pharmaceutical carrier.
Claim 16
Dependent Claim
21 words
A pharmaceutical composition comprising an effective amount of the heterogeneous population of polypeptides of claim 8 and a suitable pharmaceutical carrier.
Claim 17
Dependent Claim
27 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the composition of claim 9.
Claim 18
Dependent Claim
27 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the composition of claim 10.
Claim 19
Dependent Claim
27 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the composition of claim 11.
Claim 20
Dependent Claim
27 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the composition of claim 12.
Claim 21
Dependent Claim
27 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the composition of claim 13.
Claim 22
Dependent Claim
26 words
A method for inhibiting the growth of human tumor cells which comprises contacting the cells with an effective tumor growth-inhibiting amount of the of claim 14.
Claim 23
Dependent Claim
24 words
A method for treating a burn or healing a wound which comprises contacting the bum or wound with a pharmaceutical composition of claim 9.
Claim 24
Dependent Claim
24 words
A method for treating a burn or healing a wound which comprises contacting the bum or wound with a pharmaceutical composition of claim 10.
Claim 25
Dependent Claim
24 words
A method for treating a burn or healing a wound which comprises contacting the burn or wound with a pharmaceutical composition of claim 11.
Claim 26
Dependent Claim
24 words
A method for treating a burn or healing a wound which comprises contacting the bum or wound with a pharmaceutical composition of claim 12.
Claim 27
Dependent Claim
24 words
A method for treating a bum or healing a wound which comprises contacting the burn or wound with a pharmaceutical composition of claim 13.
Claim 28
Dependent Claim
24 words
A method for treating a bum or healing a wound which comprises contacting the burn or wound with a pharmaceutical composition of claim 14.
Claim 29
Independent Claim
165 words
A method for preparing an acidified, ethanol extract from human tissue, the acidified, ethanol extract comprising a plurality of polypeptides, each of which has a molecular weight less than about 20,000 daltons and each of which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the method comprising under suitable conditions the following steps: a. treating the tissue to produce lysed cells and removing the solubilized proteins derived from the cells; b. recovering the solubilized proteins; c. separately recovering from the solubilized proteins polypeptides having an apparent molecular weight less than about 20,000 daltons; d. assaying the separately recovered polypeptides to identify those which either inhibit the growth of human tumor cells or inhibit the growth of an established mink lung cell line (CCL64) or enhance the growth of normal human foreskin fibroblasts; and e. recovering an acidified, ethanol extract containing the polypeptides so identified.
Claim 30
Independent Claim
165 words
A method for preparing an acidified, ethanol extract from human tissue, the acidified, ethanol extract comprising a plurality of polypeptides, each of which has a molecular weight less than about 20,000 daltons and each of which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the method comprising under suitable conditions the following steps: a. treating the tissue to produce lysed cells and removing the solubilized proteins derived from the cells; b. recovering the solubilized proteins; c. separately recovering from the solubilized proteins polypeptides having an apparent molecular weight less than about 20,000 daltons; d. assaying the separately recovered polypeptides to identify those which either inhibit the growth of human tumor cells or inhibit the growth of an established mink lung cell line (CCL64) or enhance the growth of normal human foreskin fibroblasts; and e. recovering an acidified, ethanol extract containing the polypeptides so identified.
Claim 31
Independent Claim
194 words
A method for preparing an acidified, ethanol extract from human umbilical cord, the acidified, ethanol extract comprising tissue-derived growth inhibitor (TGI) which has an apparent molecular weight of about 20,000-30,000 daltons and which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the method comprising under suitable conditions the following steps: a. removing veins and arteries from the umbilical cord tissue and washing the tissue to remove all traces of blood; b. treating the tissue to produce lysed cells and removing soluble proteins derived from the cells; c. solubilizing and isolating the remaining proteins from the lysed cells to produce solubilized proteins; d. recovering the solubilized proteins; e. separately recovering from the solubilized proteins TGI having an apparent molecular weight of about 20,000-30,000 daltons; f. assaying the separately recovered TGI to identify the activity which inhibits the growth of human tumor cells, inhibits the growth of an established mink lung cell line (CCL64) and enhances the growth of normal human foreskin fibroblasts; and g. recovering the acidified, ethanol extract containing the TGI so identified.
Claim 32
Independent Claim
194 words
A method for preparing an acidified, ethanol extract from human umbilical cord, the acidified, ethanol extract comprising tissue-derived growth inhibitor (TGI) which has an apparent molecular weight of about 20,000-30,000 daltons and which has the property of inhibiting the growth of human tumor cells and of an established mink lung cell line (CCL64) while stimulating the growth of normal human foreskin fibroblasts, the method comprising under suitable conditions the following steps: a. removing veins and arteries from the umbilical cord tissue and washing the tissue to remove all traces of blood; b. treating the tissue to produce lysed cells and removing soluble proteins derived from the cells; c. solubilizing and isolating the remaining proteins from the lysed cells to produce solubilized proteins; d. recovering the solubilized proteins; e. separately recovering from the solubilized proteins TGI having an apparent molecular weight of about 20,000-30,000 daltons; f. assaying the separately recovered TGI to identify the activity which inhibits the growth of human tumor cells, inhibits the growth of an established mink lung cell line (CCL64) and enhances the growth of normal human foreskin fibroblasts; and g. recovering the acidified, ethanol extract containing the TGI so identified.
Claim 33
Dependent Claim
64 words
A method of claim 27, wherein the 'step (a) treating the tissue comprises suspending the tissue in a suitable acidic extraction buffer containing ethanol at about 4°C and homogenizing the tissue for a suitable period of time to form homogenized tissue, stirring the homogenized tissue for a suitable period at about 4°C to produced lysed cells and to solubilize proteins derived from the cells.
Claim 34
Dependent Claim
25 words
A method of claim 27, wherein the step (c) the separate recovery of polypeptides from the solubilized proteins comprises molecular sieve chromatography of the proteins.
Claim 35
Dependent Claim
75 words
A method of claim 27, wherein the step (d) assaying the polypeptides comprises separately contacting the human tumor cells, an established mink lung cell line (CCL64) or normal human foreskin fibroblasts under suitable conditions for a suitable period with the polypeptides so as to identify polypeptides which inhibit the growth of human tumor cells, inhibit the growth of the established mink lung cell line (CCI64) or which enhance the growth of normal human foreskin fibroblasts.
Claim 36
Dependent Claim
49 words
A method of claim 28, wherein the step (b) treating the tissue comprises suspending the tissue in a suitable buffer at about 4°C and homogenizing the tissue for an suitable period of time to form lysed cells and soluble proteins, and removing the soluble proteins from the lysed cells.
Claim 37
Dependent Claim
52 words
A method of claim 28, wherein step (c) solubilizing and isolating the remaining proteins from the lysed cells to produce solubilized proteins comprises suspending the lysed cells in a suitable extraction buffer at about 4°C for a suitable period to produce solubilized proteins, and isolating the solubilized proteins from the lysed cells.
Claim 38
Dependent Claim
25 words
A method of claim 28, wherein the step (e) the separate recovery of polypeptides from the solubilized proteins comprises molecular sieve chromatography of the proteins.
Claim 39
Dependent Claim
76 words
A method of claim 28, wherein the step (f) assaying the TGI comprises separately contacting the human tumor cells, an established mink lung cell line (CCL64) or normal human foreskin fibroblasts under suitable conditions for a suitable period with the TGI so as to identify the activity which inhibits the growth of human tumor cells, inhibits the growth of the established mink lung cell line (CCL64) or which enhances the growth of normal human foreskin fibroblasts.
Claim 40
Dependent Claim
83 words
A method for preparing a composition of matter designated tissue-derived growth inhibitor-1 (TGI-1) which comprises first preparing an acidified, ethanol extract according to the method of claim 27 and then recovering TGI-1 from the acidified, ethanol extract as a defined activity by high performance liquid chromatography of the acidified, ethanol extract with either i) a linear gradient of acetoni trile containing 0.05% trifluroacetic acid at about 26-34% acetonitrile or ii) a linear gradient of 2-propanol containing 0.05% trifluroacetic acid at about 17-23% 2-propanol.
Claim 41
Dependent Claim
91 words
A method for preparing a composition of matter designated tissue-derived growth inhibitor (TGI) which comprises first preparing an acidified, ethanol extract according to the method of claim 28 and then recovering TGI from the acidified, ethanol extract i) as a defined activity on high performance liquid chromatography of the acidified, ethanol extract with a linear gradient of acetonitrile containing 0.05% trifluroacetic acid at about 28-34% acetonitrile or ii) as a single peak of activity from a cation exchange resin when eluted with a linear NaCI gradient at about 0.6-0.7 M NaCI.
Claim 42
Dependent Claim
83 words
A method for preparing a composition of matter designated tissue-derived growth inhibitor-2 (TGI-2) which comprises first preparing an acidified, ethanol extract according to the method of claim 27 and then recovering TGI-2 from the acidified, ethanol extract as a defined activity by high performance liquid chromatography of the acidified, ethanol extract with either i) a linear gradient of acetonitrile containing 0.05% trifluroacetic acid at about 35-39% ac- etonotrile or ii) a linear gradient of 2-propanol containing 0.05% trifluroacetic acid at about 23-27% 2-propanol.
Claim 43
Dependent Claim
46 words
A method for preparing a heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV which comprises first preparing an acidified, ethanol extract according to the method claim 27 and then recovering the heterogeneous population of polypeptides from the acidified, ethanol extract by cation exchange chromatography.
Claim 44
Dependent Claim
11 words
The acidified, ethanol extract prepared by the method of claim 27.
Claim 45
Dependent Claim
11 words
The acidified, ethanol extract prepared by the method of claim 28.
Claim 46
Dependent Claim
8 words
TGI-1 prepared by the method of claim 36.
Claim 47
Dependent Claim
8 words
TGI prepared by the method of claim 37.
Claim 48
Dependent Claim
8 words
TGI-2 prepared by the method of claim 38.
Claim 49
Dependent Claim
15 words
The heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV prepared by claim 39.
Claim 50
Independent Claim
54 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI-1 present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 51
Independent Claim
54 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI-1 present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 52
Independent Claim
55 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI present in a sample from a sub ject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 53
Independent Claim
55 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI present in a sample from a sub ject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 54
Independent Claim
54 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI-2 present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 55
Independent Claim
54 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of TGI-2 present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 56
Independent Claim
63 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 57
Independent Claim
63 words
A method for detecting the presence of a tumor which comprises quantitatively determining the amount of heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV present in a sample from a subject and comparing the amount so determined with the amount present in a sample from a normal subject, the presence of a significantly different amount indicating the presence of a tumor.
Claim 58
Independent Claim
86 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI-1 and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI-1 present in the sample to the amount of TGF-alpha, determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 59
Independent Claim
86 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI-1 and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI-1 present in the sample to the amount of TGF-alpha, determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 60
Independent Claim
85 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI present in the sample to the amount of TGF-alpha,determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 61
Independent Claim
85 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI present in the sample to the amount of TGF-alpha,determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 62
Independent Claim
85 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI-2 and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI-2 present in the sample to the amount of TGF-alpha,determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 63
Independent Claim
85 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of TGI-2 and of transforming growth factor alpha (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of TGI-2 present in the sample to the amount of TGF-alpha,determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 64
Independent Claim
105 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of a heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV and of transforming growth factor (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of the heterologous population of polypeptides designated CM-I, CM-11, CM-III and CM-IV present in the sample to the amount of TGF-alpha, determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 65
Independent Claim
105 words
A method for detecting the presence of a tumor which comprises separately quantitatively determining the amount of a heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV and of transforming growth factor (TGF-alpha) present in a sample from a subject, determining the ratio of the amount of the heterologous population of polypeptides designated CM-I, CM-11, CM-III and CM-IV present in the sample to the amount of TGF-alpha, determining the comparable ratio for a sample from a normal subject and comparing the ratio for the subject to the ratio for the normal subject, a significant variation in the ratio indicating the presence of a tumor.
Claim 66
Independent Claim
57 words
A method for typing tumors which comprises determining for a sample from a subject with a tumor presence of one or more of TGI-1, TGI, TGI-2, or the heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV in the sample, the presence or absences of a specific combination thereof being indicative of a specific tumor type.
Claim 67
Independent Claim
57 words
A method for typing tumors which comprises determining for a sample from a subject with a tumor presence of one or more of TGI-1, TGI, TGI-2, or the heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and CM-IV in the sample, the presence or absences of a specific combination thereof being indicative of a specific tumor type.
Claim 68
Independent Claim
57 words
A method for typing tumors which comprises quantitatively determining for a sample from a subject with a tumor the amount of each of TGI-1, TGI, TGI-2 or the heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and present in the sample, the presence of specific amounts or relative amounts thereof being indicative of a specific tumor type.
Claim 69
Independent Claim
57 words
A method for typing tumors which comprises quantitatively determining for a sample from a subject with a tumor the amount of each of TGI-1, TGI, TGI-2 or the heterogeneous population of polypeptides designated CM-I, CM-II, CM-III and present in the sample, the presence of specific amounts or relative amounts thereof being indicative of a specific tumor type.
References Cited (Backward Citations)
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