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Title:
SUBCUTANEOUS MEDROXYPROGESTERONE ACETATE FOR TREATMENT OF MENOPAUSE AND ENDOMETRIOSIS
Document Type and Number:
WIPO Patent Application WO/2000/021511
Kind Code:
A2
Abstract:
One aspect of the present invention is a method of human female menopause treatment which comprises subcutaneous administration of a menopausely effective amount of a hormonal replacement agent selected from the group consisting of a progestogen and a progestogen plus an estrogen. Another aspect of the present invention is treating endometriosis.

Inventors:
DE KONING GANS HENDRIK J (US)
Application Number:
PCT/US1999/020904
Publication Date:
April 20, 2000
Filing Date:
October 06, 1999
Export Citation:
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Assignee:
UPJOHN CO (US)
KONING GANS HENDRIK J DE (US)
International Classes:
A61K31/565; A61K31/567; A61K31/57; A61P5/30; A61P5/34; A61P15/00; A61P15/12; A61P15/18; C07J7/00; (IPC1-7): A61K31/00
Domestic Patent References:
WO1993000070A11993-01-07
Foreign References:
US4826831A1989-05-02
US5814340A1998-09-29
US5753639A1998-05-19
Other References:
CONARD J ET AL: "CARDIOVASCULAR RISK FACTORS AND COMBINED ESTROGEN-PROGESTIN REPLACEMENT THERAPY: A PLACEBO-CONTROLLED STUDY WITH NOMEGESTROL ACETATE AND ESTRADIOL" FERTILITY AND STERILITY,US,ELSEVIER SCIENCE INC, NEW YORK, NY, vol. 64, no. 5, 1 November 1995 (1995-11-01), pages 957-962, XP000568559 ISSN: 0015-0282
DATABASE WPI Derwent Publications Ltd., London, GB; AN 1980-36031c XP002136712 "Endocrine gynaecological disorder treatment - by injecting oestrogen and progesterone sucutaneously in amounts depending on skin selectivity" & SU 686 736 A (OBSTETRICS RES. INSTIT.), 28 September 1979 (1979-09-28)
DATABASE WPI Derwent Publications Ltd., London, GB; AN 1980-80228c XP002136713 "Investigating functioning of ovaries - by subcutaneous injections of oestradiol, oestriol and progesterone and evaluating skin reaction" & SU 724 127 A (OBSTETRICS GYNAECOL), 30 March 1980 (1980-03-30)
J.E.F. REYNOLDS: "Martindale, The Extra Pharmacopeia" 1996 , THE ROYAL PHARMACEUTICAL SOCIETY , LONDON, UK XP002135241 page 1495, column 2 -page 1496, column 2
HALL P ET AL: "Introductory study of the once-a-month, injectable contraceptive Cyclofem in Brazil, Chile, Colombia, and Peru." CONTRACEPTION, (1997 DEC) 56 (6) 353-9., XP002136049 cited in the application
Attorney, Agent or Firm:
Stein, Bruce (MI, US)
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Claims:
CLAIMS
1. A method of human female menopause treatment which comprises subcutaneous administration of a menopausely effective amount of a hormonal replacement agent selected from the group consisting of a progestogen and a progestogen plus an estrogen.
2. A method of human female menopause treatment according to claim 1 where the progestogen is selected from the group consisting of medroxyprogesterone acetate, progesterone, norethindrone, desogestrel and levonorgestrel.
3. A method of human female menopause treatment according to claim 2 where the progestogen is medroxyprogesterone acetate.
4. A method of human female menopause treatment according to claim 1 where the estrogen is selected from the group consisting of ethinyl estradiol, estradiol cypionate and estradiol valerate.
5. A method of human female menopause treatment according to claim 4 where the estrogen is estradiol cypionate.
6. A method of human female menopause treatment according to claim 1 where the hormonal replacement agent is medroxyprogesterone acetate.
7. A method of human female menopause treatment according to claim 1 where the hormonal replacement is medroxyprogesterone acetate plus estradiol cypionate.
8. A method of human female menopause treatment according to claim 1 where when the menopausely effective amount of progestogen is administered once a month the menopausely effective amount is: for medroxyprogesterone acetate from about 10 mg to about 50 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
9. A method of human female menopause treatment according to claim 8 where the menopausely effective amount of medroxyprogesterone acetate is from about 20 mg to about 30 mg/female.
10. A method of human female menopause treatment according to claim 1 where when the menopausely effective amount of progestogen is administered every three months the menopausely effective amount is: for medroxyprogesterone acetate from about 50 mg to about 200 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
11. A method of human female menopause treatment according to claim 10 where the menopausely effective amount of medroxyprogesterone acetate is from about 75 mg to about 175 mg/female.
12. A method of human female menopause treatment according to claim 1 where when the menopausely effective amount of progestogen is administered every three months the menopausely effective amount is: for medroxyprogesterone acetate from about 100 mg to about 200 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
13. A method of human female menopause treatment according to claim 12 where the menopausely effective amount of medroxyprogesterone acetate is from about 125 mg to about 175 mg/female.
14. A method of human female menopause treatment according to claim 1 where when the menopausely effective amount of progestogen is administered every six months the menopausely effective amount is: for medroxyprogesterone acetate from about 100 mg to about 500 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
15. A method of human female menopause treatment according to claim 14 where the menopausely effective amount of medroxyprogesterone acetate is from about 150 mg to about 300 mg/female.
16. A method of human female menopause treatment according to claim 1 where when the menopausely effective amount of progestogen is administered every six months the menopausely effective amount is: for medroxyprogesterone acetate from about 200 mg to about 500 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
17. A method of human female menopause treatment according to claim 16 where the menopausely effective amount of medroxyprogesterone acetate is from about 250 mg to about 300 mg/female.
18. A method of human female menopause treatment according to claim 1 where both the progestogen and estrogen are administered once every month the menopausely effective amount of progestogen is for medroxyprogesterone acetate from about 10 mg to about 50 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female. and the menopausely effective amount of estrogen is for estradiol cypionate from about 2.5 mg to about 20 mg/female, ethinyl estradiol from about 0.5 mg to about 3 mg/female, estradiol valerate from about 2.5 mg to about 20 mg/female.
19. A method of human female menopause treatment according to claim 18 where the menopausely effective amount of medroxyprogesterone acetate is from about 20 mg to about 30 mg/female and the menopausely effective amount of estradiol cypionate is from about 3 to about 10 mg/female.
20. A method of human female menopause treatment according to claim 1 where the menopausely effective amount of progestogen is administered either approximately every 3 or approximately every 6 months.
21. A method of human female menopause treatment according to claim 1 where the menopause treatment is for premenopause.
22. A method of human female menopause treatment according to claim 1 where the menopause treatment is for menopause.
23. A method of human female rnenopause treatment according to claim 1 where the menopause treatment is for postmenopause.
24. A method of human female menopause treatment according to claim 1 where the subcutaneous administration of the menopausely effective amount of a hormonal replacement agent is by self administration.
25. A method of treating endometriosis in a human female who is in need of such treatment which comprises subcutaneous administration of a endometrially effective amount of a progestogen.
26. A method of treating endometriosis in a human female according to claim 25 where the progestogen is selected from the group consisting of medroxyprogesterone acetate, progesterone, norethindrone, desogestrel and levonorgestrel.
27. A method of treating endometriosis in a human female according to claim 26 where the progestogen is medroxyprogesterone acetate.
28. A method of treating endometriosis in a human female according to claim 25 where when the endometrially effective amount of progestogen is administered once a month and is: for medroxyprogesterone acetate from about 10 mg to about 50 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
29. A method of treating endometriosis in a human female according to claim 28 where the endometrially effective amount of medroxyprogesterone acetate is from about 20 mg to about 30 mg/female.
30. A method of treating endometriosis in a human female according to claim 25 where when the endometrially effective amount of progestogen is administered every three months and is: for medroxyprogesterone acetate from about 50 mg to about 200 mg/femaie, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
31. A method of treating endometriosis in a human female according to claim 30 where the endometrially effective amount of medroxyprogesterone acetate is from about 75 mg to about 175 mg/female.
32. A method of treating endometriosis in a human female according to claim 25 where when the endometrially effective amount of progestogen is administered every three months and is: for medroxyprogesterone acetate from about 100 mg to about 200 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
33. A method of treating endometriosis in a human female according to claim 32 where the endometrially effective amount of medroxyprogesterone acetate is from about 125 mg to about 175 mg/female.
34. A method of treating endometriosis in a human female according to claim 25 where when the endometrially effective amount of progestogen is administered every six months an is: for medroxyprogesterone acetate from about 100 mg to about 500 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
35. A method of treating endometriosis in a human female according to claim 34 where the endometrially effective amount of medroxyprogesterone acetate is from about 150 mg to about 300 mg/female.
36. A method of treating endometriosis in a human female according to claim 25 where when the endometrially effective amount of progestogen is administered every six months an is: for medroxyprogesterone acetate from about 200 mg to about 500 mg/female, for progesterone from about 25 mg to about 200 mg/female, for northindrone from about 5 mg to about 50 mg/female, for desogestrel from about 1 mg to about 4 mg/female, for levonorgrestrel from about 0.5 mg to about 2 mg/female.
37. A method of treating endometriosis in a human female according to claim 36 where the endometrially effective amount of medroxyprogesterone acetate is from about 250 mg to about 300 mg/female.
38. A method of treating endometriosis in a human female according to claim 25 where the endometrially effective amount of progestogen is administered either approximately every 3 or approximately every 6 months.
39. A method of treating endometriosis in a human female according to claim 25 where the endometrially effective amount of progestogen is administered by self administration.
Description:
INTERNATIONALSEARCHREPORTlntelonalApplication No PCT/US99/20904 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category ° Citationofdocument,withindication,whereappropriate,oftherele vantpassagesRelevanttoclaimNo. XUS4826831A(WOLFEBERNARDMJETAL)1-3,6, 2May1989(1989-05-02)8-11,13, citedintheapplication16 column3,line11-18 column6,line28-30;tables1A-lC claims XUS5814340A(LEPAGEMARTINETAL)1-3,6, 29September1998(1998-09-29)8-11,13, 16 column1,line13-30 column13,line40-48 column13,line59-64 column15,line14-32 column27,line55-64 column31,line10-14 examples11,12 XUS5753639A(LABRIEFERNAND)1-3,6, 19May1998(1998-05-19)8-11,13, 16 column10,line23-27 column10,line41-44 column18,line4-8 column19,line66-column20,line7; claims;examples ACONARDJETAL:"CARDIOVASCULARRISK1-3,6, FACTORSANDCOMBINEDESTROGEN-PROGESTIN8-11,13, REPLACEMENTTHERAPY:APLACEBO-CONTROLLED16 STUDYWITHNOMEGESTROLACETATEAND ESTRADIOL" FERTILITYANDSTERILITY,US,ELSEVIER SCIENCEINC,NEWYORK,NY, vol.64,no.5, 1November1995(1995-11-01),pages 957-962,XP000568559 ISSN:0015-0282 thewholedocument YDATABASEWPI1-3,6, DerwentPublicationsLtd.,London,GB;8-11,13, AN1980-36031c16 XP002136712 "Endocrinegynaecologicaldisorder treatment-byinjectingoestrogenand progesteronesucutaneouslyinamounts dependingonskinselectivity" &SU686736A(OBSTETRICSRES.INSTIT.), 28September1979(1979-09-28) abstract 7 INTERNATIONALSEARCHREPORTintiional Application No PCT/US99/20904 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category°Citationofdocument,withindication,whereappropriate ,oftherelevantpassagesRelevanttoclaimNo. Y DATABASE WPI 1-3, 6, DerwentPublicationsLtd.,London,GB;8-11,13, AN1980-80228c16 XP002136713 "Investigatingfunctioningofovaries- bysubcutaneousinjectionsofoestradiol, oestriolandprogesteroneandevaluating skinreaction" &SU724127A(OBSTETRICSGYNAECOL), 30March1980(1980-03-30) abstract AJ.E.F.REYNOLDS:"Martindale, TheExtra1-3,6, Pharmacopeia"8-11,13, 1996,THEROYALPHARMACEUTICALSOCIETY,16 LONDON,UKXP002135241 page1495,column2-page1496,column2 AHALLPETAL:"Introductorystudyofthe1-3,6, once-a-month,injectablecontraceptive8-11,13, CyclofeminBrazil,Chile,Colombia,and16 Peru." CONTRACEPTION,(1997DEC)56(6)353-9., XP002136049 citedintheapplication thewholedocument 7 ....arnationalapplicationNo. INTERNATIONALSEARCHREPORTPCT/US99/20904 BoxIObservationswherecertainclaimswerefoundunsearchable(Cont inuationofitem1offirstsheet) This IntemationalSearchReporthasnotbeenestablishedinrespectofcert ainclaimsunderArticle17(2)(a)forthefollowingreasons: 1.jClaims Nos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: seeFURTHERINFORMATIONsheetPCT/ISA/210 2.jjClaimsNos.: becausetheyrelatetopartsoftheInternationalApplicationthatdon otcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulinternationalSearchcanbecarriedout,s pecifically: 3.ClaimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisInternationalSearchingAuthorityfoundmultipleinventionsin thisinternationalapplication,asfollows: 1.As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant, thisInternationalSearchReportcoversall searchableclaims. 2.FAsallsearchableclaimscouldbesearchedwithouteffortjustifyi nganadditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionaltee. 3.! ! As on ! y someoftherequiredadditionalsearchfeesweretimelypaidbytheappl icant,thisInternationalSearchReport covers onlythoseclaimsforwhichfeeswerepaid,specificallyclaimsNos.: 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims;itiscovere dbyclaimsNos.: 1,2,8,10,12,14,16,20-24(part)3,6,9,11,13,15,17,19(complete) RemarkonProtest! ! The additionalsearchfeeswereaccompaniedbytheapplicant'sprotest. u FNoprotestaccompaniedthepaymentofadditionalsearchfees. u FURTHER INFORMATION CONTINUED FROM PCTSA/210 1. Claims: Claims: 1,2,8,10,12,14,16,20-24 (partial); 3,6,9, 11,13,15,17,19 (complete).

Pharmaceutical composition for the subcutaneous administration of medroxyprogesterone acetate for use in relation to the treatment of conditions related to menopause.

2. Claims: Claims 1,2,8,10,12,14,16, 20- 24 (partial) (As far as not comprised in the previo us invention) Pharmaceutical composition for the subcutaneous administration of progesterone for use in relation to the treatment of conditions related to menopause.

3. Claims: Claims 1,2,8,10,12,14,16, 20- 24 (partial) (As far as not comprised in the previo us inventions) Pharmaceutical composition for the subcutaneous administration of norethindrone for use in relation to the treatment of conditions related to menopause.

4. Claims: Claims 1,2,8,10,12,14,16, 20- 24 (partial) (As far as not comprised in the previ ous inventions) Pharmaceutical composition for the subcutaneous administration of desogestrel for use in relation to the treatment of conditions related to menopause.

5. Claims: Claims 1,2,8,10,12,14,16, 20- 24 (partial) (As far as not comprised in the previ ous inventions) Pharmaceutical composition for the subcutaneous administration of levo-norgestrel for use in relation to the treatment of conditions related to menopause.

6. Claims: Claims 1,2,3,6,8,9,10,11,12,13,14,15,16,17, 20-24 (partial); 4,5,7,18, FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 19 (complete). (As far as not comprised in the pre vious inventions) Pharmaceutical composition for the subcutaneous administration of a progestogen plus an estrogen for use in relation to the treatment of conditions related to menopause.

7. Claims: Claims 25,26,28,30,32,34,36,38,39 (partial); 27,29, 31,33,35, 37 (complete). (As far as not comprised in the prev ious inventions) Pharmaceutical composition for the subcutaneous administration of medroxyprogestogen actetate, for use in relation to the treatment of endometriosis.

8. Claims: Claims 25,26,28,30,32,34,36,38,39 (partial).

Pharmaceutical composition for the subcutaneous administration of progesterone, for use in relation to the treatment of endometriosis.

9. Claims: Claims 25,26,28,30,32,34,36,38,39 (partial).

Pharmaceutical composition for the subcutaneous administration of norethindrone, for use in relation to the treatment of endometriosis.

10. Claims: Claims 25,26,28,30,32,34,36,38,39 (partial).

Pharmaceutical composition for the subcutaneous administration of desogestrel, for use in relation to the treatment of endometriosis.

11. Claims: Claims 25,26,28,30,32,34,36,38,39 (partial).

Pharmaceutical composition for the subcutaneous administration of levo-norgestrel, for use in relation to the treatment of endometriosis.

FURTHER INFORMATION CONTINUED FROM PCTIISAI 210 Continuation of Box I. 1 Although claims 1-16 are directed to a method of treatment of the human/animal body, the search has been carried out and based on the alleged effects of the compound/composition.

The wording of claim 1"progestogen"and"progestogen plus an estrogen" relates to an extremely large number of possible compounds.

Support within the meaning of Article 6 PCT and/or disclosure within the meaning of Article 5 PCT is to be found, however, for only a very small proportion of the compounds claimed. In the present case, the claim so lack support, and the application so lacks disclosure, that a meaningful search over the whole of the claimed scope is impossible. Consequently, the search for the first invention has been carried out for those parts of the claim which appear to be clear, concise, supported and disclosed, namely for the compound medroxyprogesterone acetate, with due regard to the general idea underlying the application. INTERNATIONALSEARCHREPORT !----------------- ! Inte fonal ApplicationNo Informationonpatentfamilymembers PCT/US 99/20904 PatentdocumentPublic on Patent family citedin searchreportdate member(s)date WO9300070A07-01-1993HU 66859 A 30-01-1995 US 5434146 A 18-07-1995 AU 2182092 A 25-01-1993 CA 2112393 A 07-01-1993 CZ 9302908 A 19-10-1994 EP 0591311 A 13-04-1994 JP 6508624 T 29-09-1994 NO 934742 A 21-12-1993 PL 297867 A 07-02-1994 US 5362720 A 08-11-1994 AT 161173 T 15-01-1998 AU 672750 B 17-10-1996 AU 707401 B 08-07-1999 AU 6587996 A 19-12-1996 CZ 285972 B 15-12-1999 DE 69223620 D 29-01-1998 DE 69223620 T 23-04-1998 FI 935893 A 28-12-1993 IL 102447 A 10-03-1998 NZ 243370 A 27-02-1996 NZ 264279 A 28-05-1996 NZ 272633 A 24-06-1997 SK 147893 A 07-09-1994 US 5545634 A 13-08-1996 US 5629303 A 13-05-1997 US 5541172 A 30-07-1996 US 5846960 A 08-12-1998 US 5567695 A 22-10-1996 US 5814340 A 29-09-1998 US 5861387 A 19-01-1999 US 5753639 A 19-05-1998 ZA 9204811 A 29-12-1993 RU 2142276 C 10-12-1999 US4826831A02-05-1989AT 147987 T 15-02-1997 CA 1240927 A 23-08-1988 DE 3486442 D 06-03-1997 DE 3486442 T 05-06-1997 DK 377084A,B 06-02-1985 EP 0136011 A 03-04-1985 IL 72556 A 15-05-1989 LU 90107 A 17-12-1997 LU 90343 A 29-03-1999 MX 9203720 A 31-07-1992 NZ 209066 A 08-01-1988 PH 24052 A 05-03-1990 US RE36247 E 06-07-1999 AU 582540 B 06-04-1989 AU 3140584 A 07-02-1985 JP 6035388 B 11-05-1994 JP 60100520 A 04-06-1985 ZA 8406077 D 27-03-1985 US5814340A29-09-1998US 5629303 A 13-05-1997 US 5434146 A 18-07-1995 US 5541172 A 30-07-1996 US 5861387 A 19-01-1999 AT 161173 T 15-01-1998 INTERNATIONALSEARCHREPORT Inte onal Application No Informationonpatentfamilymembers pCT/US 99/20904 PatentdocumentPublication Patent citedinsearchreportdate member(s)date US5814340AAU 672750 B 17-10-1996 AU 2182092 A 25-01-1993 AU 707401 B 08-07-1999 AU 6587996 A 19-12-1996 CA 2112393 A 07-01-1993 WO 9300070 A 07-01-1993 CZ 9302908 A 19-10-1994 CZ 285972 B 15-12-1999 DE 69223620 D 29-01-1998 DE 69223620 T 23-04-1998 EP 0591311 A 13-04-1994 FI 935893 A 28-12-1993 HU 66859 A 30-01-1995 IL 102447 A 10-03-1998 JP 6508624 T 29-09-1994 NO 934742 A 21-12-1993 NZ 243370 A 27-02-1996 NZ 264279 A 28-05-1996 NZ 272633 A 24-06-1997 PL 297867 A 07-02-1994 RU 2142276 C 10-12-1999 SK 147893 A 07-09-1994 US 5362720 A 08-11-1994 US 5545634 A 13-08-1996 US 5846960 A 08-12-1998 US 5567695 A.22-10-1996 US 5753639 A 19-05-1998 ZA 9204811 A 29-12-1993 US5753639A19-05-1998US 5545634 A 13-08-1996 US 5362720 A 08-11-1994 US 5846960 A 08-12-1998 US 5567695 A 22-10-1996 AT 161173 T 15-01-1998 AU 672750 B 17-10-1996 AU 2182092 A 25-01-1993 AU 707401 B 08-07-1999 AU 6587996 A 19-12-1996 CA 2112393 A 07-01-1993 WO 9300070 A 07-01-1993 CZ 9302908 A 19-10-1994 CZ 285972 B 15-12-1999 DE 69223620 D 29-01-1998 DE 69223620 T 23-04-1998 EP 0591311 A 13-04-1994 FI 935893 A 28-12-1993 HU 66859 A 30-01-1995 IL 102447 A 10-03-1998 JP 6508624 T 29-09-1994 NO 934742 A 21-12-1993 NZ 243370 A 27-02-1996 NZ 264279 A 28-05-1996 NZ 272633 A 24-06-1997 SK 147893 A 07-09-1994 US 5629303 A 13-05-1997 US 5541172 A 30-07-1996 US 5814340 A 29-09-1998 US 5861387 A 19-01-1999 INTERNATIONALSEARCHREPORT----------------- ! Inte onal ApplicationNo Informationonpatentfamilymembers PCT/US 99/20904 PCT/US99/20904 PatentdocumentPublication Patent family Publication citedinsearchreportdatemember(s)date US5753639AUS5434146A18-07-1995 ZA9204811A29-12-1993 SU686736A25-09-1979NONE SU724127A30-03-1980NONE




 
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