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Compounds and methods

Assignee: Pharmacia and Upjohn Co
•
Filing: 1979-04-26
•
Granted: 1980-08-19
•
Expires: 1999-04-26
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Abstract

Abstract A method for the radioimmunoassay of PGE 1 -type and PGE 2 -type compounds and PGX is disclosed which utilizes antibodies formed against a prostaglandin mimic. Conjugates are disclosed which are formed by attaching a prostaglandin mimic to a carrier molecule. Antibodies are disclosed which are specific against PGE 1 -type and PGE 2 -type compounds, PGH 2 , and PGX. Complexes are disclosed which are formed by binding an antibody raised against a prostaglandin mimic with its corresponding authentic prostaglandin.

Inventors

  • 👤 Francis A. Fitzpatrick

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-08 00:43
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/88; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; C; C07; C07K; C07K16/00; C07K16/18; C07K16/26; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10S436/815; Y10S436/823; Y10S530/00; Y10S530/806

Claims Analysis

Total Claims: 33
Claim 1
Independent Claim 307 words
An antibody extracted from a mammal or bird after innoculation with a conjugate formed from a carrier molecule selected from the group natural protein, synthetic polypeptide, and other macromolecular immunogen of molecular weight greater than 2,000 and less than 500,000 and a compound selected from the group ##STR26## wherein M 1 is ##STR27## wherein R 5 is hydrogen or methyl; wherein L 1 is ##STR28## or a mixture of ##STR29## wherein R 3 and R 4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R 3 and R 4 is fluoro only when the other is hydrogen or fluoro; wherein Z 1 is (1) cis--CH═CH--CH 2 --(CH 2 )g--CH 2 --, (2) cis--CH═CH--CH 2 --(CH 2 )g--CF 2 --, (3) cis--CH 2 --CH═CH--(CH 2 )g--CH 2 --, (4) --(CH 2 ) 3 --(CH 2 )g--CH 2 --, (5) --(CH 2 ) 3 --(CH 2 )g--CF 2 --, (6) --CH 2 --O--CH 2 --(CH 2 )g--CH 2 --, (7) --C═C--CH 2 --(CH 2 )g--CH 2 --, (8) --CH 2 --C═C--(CH 2 )g--CH 2 --, ##STR30## wherein g is one, 2, or 3; wherein R 7 is ##STR31## wherein m is one to 5, inclusive; n is zero or one; T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive; and s is zero, one, 2 or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that R 7 is ##STR32## wherein T and s are as defined above, only when R 3 and R 4 are hydrogen or methyl, being the same or different; and wherein X 1 is --COOR 1 wherein R 1 is hydrogen or a pharmacologically acceptable cation.
Claim 2
Dependent Claim 307 words
An antibody extracted from a mammal or bird after innoculation with a conjugate formed from a carrier molecule selected from the group natural protein, synthetic polypeptide, and other macromolecular immunogen of molecular weight greater than 2,000 and less than 500,000 and a compound selected from the group ##STR26## wherein M 1 is ##STR27## wherein R 5 is hydrogen or methyl; wherein L 1 is ##STR28## or a mixture of ##STR29## wherein R 3 and R 4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R 3 and R 4 is fluoro only when the other is hydrogen or fluoro; wherein Z 1 is (1) cis--CH═CH--CH 2 --(CH 2 )g--CH 2 --, (2) cis--CH═CH--CH 2 --(CH 2 )g--CF 2 --, (3) cis--CH 2 --CH═CH--(CH 2 )g--CH 2 --, (4) --(CH 2 ) 3 --(CH 2 )g--CH 2 --, (5) --(CH 2 ) 3 --(CH 2 )g--CF 2 --, (6) --CH 2 --O--CH 2 --(CH 2 )g--CH 2 --, (7) --C═C--CH 2 --(CH 2 )g--CH 2 --, (8) --CH 2 --C═C--(CH 2 )g--CH 2 --, ##STR30## wherein g is one, 2, or 3; wherein R 7 is ##STR31## wherein m is one to 5, inclusive; n is zero or one; T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive; and s is zero, one, 2 or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that R 7 is ##STR32## wherein T and s are as defined above, only when R 3 and R 4 are hydrogen or methyl, being the same or different; and wherein X 1 is --COOR 1 wherein R 1 is hydrogen or a pharmacologically acceptable cation.
Claim 3
Dependent Claim 31 words
The antibody of claim 1 where the carrier molecule is selected from the group mammal or bird albumin, mammal or bird globulin, poly-1-lysine, and polypeptide of molecular weight greater than 2500.
Claim 4
Dependent Claim 17 words
The antibody of claim 2 where the carrier molecule is keyhole limpet hemocyanin or bovine serum albumin.
Claim 5
Dependent Claim 46 words
An antibody of claim 1 where the mimic is of a PGE-type compound and the serum extracted, at a dilution of at least 1:100, binds at least 25% of the radiolabeled form of the authentic PG corresponding to the hapten used and to elicit the antibody.
Claim 6
Dependent Claim 30 words
The antibody of claim 4 where the serum extracted, at a dilution by volume of at least 1:100, binds at least 50±3% of the radiolabeled form of the authentic PG.
Claim 7
Dependent Claim 12 words
The antibody of claim 5 wherein the dilution is at least 1:1000.
Claim 8
Dependent Claim 15 words
The antibody of claim 5 wherein the PG mimic is a 9-deoxy-9-methylene-PGF 1 -type compound.
Claim 9
Dependent Claim 15 words
The antibody of claim 5 where the PG mimic is a 9-deoxy-9-methylene-PGF 2 -type compound.
Claim 10
Dependent Claim 15 words
The antibody of claim 5 where the PG mimic is a compound of Formula V.
Claim 11
Dependent Claim 15 words
The antibody of claim 9 where the PG mimic is a 9-deoxy-9-methylene-PGF 1 -type compound.
Claim 12
Dependent Claim 13 words
The antibody of claim 10 where the PG mimic is 9-deoxy-9-methylene-PGF 1 .
Claim 13
Dependent Claim 15 words
The antibody of claim 9 where the PG mimic is a 9-deoxy-9-methylene-PGF 2 -type compound.
Claim 14
Dependent Claim 14 words
The antibody of claim 12 where the PG mimic is 9-deoxy-9-methylene PGF 2 .
Claim 15
Dependent Claim 13 words
The antibody of claim 12 where the PG mimic is 9-deoxy-9-methylene-15(R)-15-methyl-PGF 2 .
Claim 16
Dependent Claim 13 words
The antibody of claim 12 where the PG mimic is 9-deoxy-9-methylene-15(S)-15-methyl-PGF 2 .
Claim 17
Dependent Claim 43 words
The antibody of claim 2 where the PG mimic is (5Z,9α,11α,13E,15S)-9,11-azo-15-hydroxyprosta-5,13-dien-1-oic acid and no more than 100 μl. of the serum extracted delays platelet aggregation (1.0 ml. PRP; 400 μg. arachidonic acid) for 1 minute at the midpoint of the maximum aggregatory response.
Claim 18
Dependent Claim 15 words
The antibody of claim 16 where no more than 50 μl. of antiserum delays aggregation.
Claim 19
Dependent Claim 44 words
The antibody of claim 2 where the PG mimic is 9-deoxy-6,9α-epoxy-PGF 1 α and no more than 50 μl. of the serum extracted restores the platelet aggregation (2.0 ml. PRP; 1000 μg. arachidonic acid) blocked by 0.050 μg. PGX in less than 10 minutes.
Claim 20
Dependent Claim 16 words
The antibody of claim 18 where no more than 30 μl. of the antiserum restores aggregation.
Claim 21
Dependent Claim 26 words
A complex formed by binding an antibody raised against a PG mimic of formula II, III, or IV of claim 1 with its corresponding authentic prostaglandin.
Claim 22
Dependent Claim 14 words
The complex of claim 20 where the mimic is a compound of formula IV.
Claim 23
Dependent Claim 14 words
The complex of claim 21 where the mimic is a 9-deoxy-9-methylene-PGF 1 -type compound.
Claim 24
Dependent Claim 14 words
The complex of claim 21 where the mimic is a 9-deoxy-9-methylene-PGF 2 -type compound.
Claim 25
Dependent Claim 14 words
The complex of claim 21 where the mimic is a compound of formula V.
Claim 26
Dependent Claim 14 words
The complex of claim 24 where the mimic is a 9-deoxy-9-methylene-PGF 1 -type compound.
Claim 27
Dependent Claim 12 words
The complex of claim 25 where the mimic is 9-deoxy-9-methylene-PGF 1 .
Claim 28
Dependent Claim 14 words
The complex of claim 24 where the mimic is a 9-deoxy-9-methylene-PGF 2 -type compound.
Claim 29
Dependent Claim 12 words
The complex of claim 27 where the mimic is 9-deoxy-9-methylene-PGF 2 .
Claim 30
Dependent Claim 13 words
The complex of claim 27 where the mimic is 9-deoxy-9-methylene-15(R)-15-methyl PGF 2 .
Claim 31
Dependent Claim 14 words
The complex of claim 27 where the PG mimic is 9-deoxy-9-methylene-15(S)-15-methyl PGF 2 .
Claim 32
Dependent Claim 11 words
The complex of claim 20 where the mimic is (5Z,9α,11α,13E,15S)-9,11-azo-15-hydroxyprosta-5,13-dien-1-oic acid.
Claim 33
Dependent Claim 12 words
The complex of claim 20 where the mimic is 9-deoxy-6,9α-epoxy-PGF 1 α.

References Cited (Backward Citations)

US3867366A Cited
US3980764A Cited
US4041076A Cited
US3950363A Cited
US4053459A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1983-08-19 1984-02-18 1984-08-19 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1987-08-19 1988-02-18 1988-08-19 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1991-08-19 1992-02-18 1992-08-19 $7700.00 Window Closed / Lapsed

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