FarmaPatent Limited
http://www.farmapatent.com.tr
IPTS 2008
Pharmaceutical Patents
Dr.Ecz. PINAR BULUT
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CERN
"Big Bang“ Experiment
10 September 2008
Gravitons and Bosons "Missing Dark Matter“
Higgs particles
Electronic Orange Book
Patent Data
Patent
No
*
Patent
Expiration
Drug
Substance
Claim
Drug Product
Claim
Patent Use
Code
4687777
Jan 17, 2011
Y
6150383
Jun 19, 2016
U-753
6211205
Jun 19, 2016
U-753
6303640
Aug 9, 2016
U-753
6329404
Jun 19, 2016
Exclusivity Data
There is no unexpired exclusivity for this product.
* GLIMEPIRIDE; PIOGLITAZONE HYDROCHLORIDE
Y
U-753
Marketing Exclusivity Codes:
New Combination
New Chemical Entity
New Dosage Form
New Ester or Salt of an Active
Ingredient
New Product
New Route
New Strength
The patents that FDA regards as claiming these drug patents are:
1) Patents that claim the active ingredient(s)
2) Drug product patent, which include formulation/composition patents
3) Use patents for a particular approved indication or method of using
the product.
Council Regulation (EEC) No 1768/92 of 18 June 1992
concerning the creation of a supplementary protection
certificate for medicinal products
Article 3 . Conditions for obtaining a certificate
A certificate shall be granted if, in the Member State in which the application referred to
in Article 7 is submitted and at the date of that application:
(a) the product is protected by a basic patent in force;
Article 1 . Definitions For the purposes of this Regulation:
(a) 'medicinal product' means any substance or combination of substances presented
for treating or preventing disease in human beings or animals …..;
(b) 'product' means the active ingredient or combination of active ingredients of a
medicinal product;
(c) 'basic patent' means a patent which protects a product as defined in (b) as
such, a process to obtain a product or an application of a product, and which is
designated by its holder for the purpose of the procedure for grant of a
certificate;
Supplementary Protection Certificate (SPC)
SPC number: SPC/GB02/049
Patent No: EP0347066 (New Enantiomers and Their Isolation )
Community authorisation: Sweden (7 December 2001)
Product description: Escitalopram oxalate
Supplementary Protection Certificate
SPC number: SPC/GB01/053
Patent No: EP 0397831 (Treatment of Obesity )
Community authorisation: Germany (14 January 1999)
Product description: Sibutramine hydrochloride monohydrate
Claims
1. The use of N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine
hydrochloride in the manufacture of a medicament for the treatment of obesity.
2. The use of N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine
hydrochloride monohydrate in the manufacture of a medicament for the treatment
of obesity.
CAUTION !
*
For most Generic Drug
Developments,
Molecule Patent
expiry dates are the
‘Tip of the Iceberg’
* Presented by Leighton Howard – ICSE2005 , Madrid
Secondary Patents (Evergreening)
Drug Substance
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Polymorphs
Salt/Hydrate/Solvate
Prodrug, Metabolite
Impurity Profile, Substantially pure
Physicochemical properties
Particle size
Synthetic Route
New intermediates, Starting
materials, Catalysts
Purification Method
Assay Technique
Drug Product
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Formulation / Composition
Combination
Manufacturing method
Excipients
Packaging
Medical Use
Route of Administration
Dosing Regimen
POLYMORPH PATENTS (Donepezil – EISAI)
Claims
1. Donepezil hydrochloride ………….. in the form of polymorph (III), being
specified ……… X-ray diffraction pattern and ……… infrared absorption
spectra ……….
POLYMORPH PATENTS (Rosiglitazone – SKB)
Claims
1. A polymorphic form of …… maleic acid salt (the Polymorph)
characterised in that it provides:
(i) an infrared spectrum containing peaks at ………. ; and/or
(ii) a Raman spectrum containing peaks at ………. ; and/or
(iii) a solid-state 13C NMR spectrum containing peaks at ……; and/or
(iv) an XRPD pattern ……………
PSEUDOPOLYMORPH (Hydrate) - (Rosiglitazone – SKB)
Scientific Considerations of Polymorphism in Pharmaceutical
Solids: Abbreviated New Drug Applications *
•
POLYMORPHISM IN PHARMACEUTICAL SOLID DRUG SUBSTANCE
AND THE ISSUE OF "SAMENESS“
•
A drug substance in a generic drug product is generally considered to
be the same as the drug substance in the reference listed drug if it meets
the same standards for identity. In most cases, the standards for identity
are described in the USP although FDA may prescribe additional
standards when necessary.
•
Because drug product performance depends on the product formulation,
the drug substance in a proposed generic drug product need not have
the same physical form (particle size, shape, or polymorph form) as the
drug substance in the reference listed drug.
* FDA
Scientific Considerations of Polymorphism in Pharmaceutical
Solids: Abbreviated New Drug Applications *
•
An ANDA applicant is required to demonstrate that the proposed product
meets the standards for identity, exhibits sufficient stability and is
bioequivalent to the reference listed drug.
•
Over the years FDA has approved many generic drug products based
upon a drug substance with different physical form from that of the drug
substance in the respective reference listed drug (e.g., warfarin sodium,
famotidine, and ranitidine).
•
Also many ANDAs have been approved in which the drug substances
differed from those in the corresponding reference listed drugs with
respect to solvation or hydration state (e.g., terazosin hydrochloride,
ampicillin, and cefadroxil).
* FDA
CASE 1: RANITIDINE
1.
Form 2 ranitidine hydrochloride characterised by an infra-red
spectrum as a mull in mineral oil showing the following main peaks:
RANITIDINE: Patents and Generics
Patent No.
Coverage
Expiry Date
US 4128658
Ranitidine Form I
25/07/1997
US 4521431
Ranitidine Form II
09/08/2002
Product
Approval Date
Zantac 150 mg Tablet (GLAXO)
Zantac 300 mg Tablet (GLAXO)
09/06/1983
09/12/1985
TEVA Ranitidine Tablets
31/07/1997
SANDOZ Ranitidine Tablets
29/08/1997
TORPHARM Ranitidine Tablets
12/09/1997
WATSON Ranitidine Tablets
20/10/1997
PATENT ACT (INDIA) Amendment (5th April 2005)
INVENTIONS NOT PATENTABLE
3. What are not inventions
“(d) the mere discovery of a new form of a known substance which does not result in
the enhancement of the known efficacy of that substance or the mere discovery of
any new property or new use for a known substance or of the mere use of a known
process, machine or apparatus unless such known process results in a new product
or employs at least one new reactant.
Explanation – For the purposes of this clause, salts, esters, ethers,
polymorphs, metabolites, pure form, particle size, isomers, mixtures of
isomers, complexes, combinations and other derivatives of known substance
shall be considered to be the same substance, unless they differ significiantly
in properties with regard to efficacy.”
European
Patent Office
RESULT LIST
Approximately 662 results found in the Worldwide database for:
polymorp* in the title or abstract AND
wo as the publication number AND
C07D as the IPC classification
Search International Patent Applications
Results of searching in PCT for:
ABSTRACT:
POLYMORPH OR POLYMORPHS OR POLYMORPHISM
PRIORITY COUNTRY: INDIA
IPC:
C07D
99 records
Search International Patent Applications
Results of searching in PCT for:
ABSTRACT: POLYMORPH OR POLYMORPHS OR POLYMORPHISM
IPC: A61K
APPLICANT: TEVA
7 records
APPLICANT: PFIZER
12 records
APPLICANT: ROCHE
3 records
Results of Search in US Patent Collection db for:
(ACLM/(crystalline AND form) AND a61k): 184 patents.
ISOMERIC FORM, SALT and HYDRATE
Claims
1. The magnesium salt of (-)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2pyridinyl)methyl)sulfinyl]-1H-benzimidazole (Mg-salt of the (-) enantiomer
of omeprazole)
Claims
1. The magnesium salt of S-omeprazole trihydrate
IMPURITY
Claims
1. Use of escitalopram comprising less than 3% w/w of R-citalopram
for the preparation of a pharmaceutical composition.
METABOLITES
TERFENADINE
(SELDANE)
FEXOFENADINE
(ALLEGRA)
Patent No.
US 3878217
US4254129
Filed:
July 12, 1973
Apr. 10, 1979
Publication :
Apr. 15, 1975
Mar. 3, 1981
Expiry Date:
Apr. 15, 1994 (Extended)
Feb. 17, 2001 (Extended)
Approval Date:
HO C
OH
H2 H2
N C C CH2 C
H
Jul 25, 1996 (60 mg Cap)
CH3
C CH3
CH3
HO C
OH
H 2 H2
N C C CH2 C
H
CH3
C COOH
CH3
FDA
TALK PAPER
Feb. 27, 1998
SELDANE AND GENERIC TERFENADINE WITHDRAWN FROM MARKET
Hoescht Marion Roussel and Baker Norton Pharmaceuticals have voluntarily
discontinued distribution and marketing of all terfenadine-containing
antihistamine product lines in the United States.
Terfenadine-containing products, such as Seldane and Seldane-D, have
been associated with rare, but serious heart problems when taken with
certain other drugs, including certain antibiotics and antifungals.
In January 1997, FDA proposed removing all terfenadine products from the
marketplace because of the approval of a safer alternative drug: Allegra
(fexofenadine hydrochloride).
SUBSTANTIALLY PURE
I . R-Tolterodine tartrate having less than about 0.5% area by HPLC of total
impurities.
13. An HPLC method comprising the steps of:
(a) combining an R- Tolterodine tartrate sample with a mixture of acetonitrile: water …
(b) injecting the solution into a …. column ……
(c) gradient eluting the sample from the column at about 8 min using a mixture of ……
(d) measuring the impurity content in the relevant sample with a UV detector …..
FORMULATIONS – COMPOSITIONS - EXCIPIENTS
Clopidogrel bisulfate tablet formulation
1. A pharmaceutical tablet which comprises clopidogrel bisulfate and a lubricant
selected from the group consisting of zinc stearate, sodium stearyl fumarate and
stearic acid.
Dry Mix Formulation for Bisphosphonic acids
1. A pharmaceutical composition comprising from 0.5 to 40% by weight of 4-amino-1hydroxybutylidene-1,1-bisphosphonic acid or a pharmaceutical acceptable salt thereof
and from 60 to 99.5% by weight of excipients, said excipients comprising a diluent
selected from anhydrous lactose or hydrous fast flow lactose, a dry binder, a
disintegrant, and a lubricant.
COMBINATIONS
1. Pharmaceutical composition which comprises an insulin sensitivity
enhancer selected from pioglitazone or a pharmaceutically acceptable salt
thereof in combination with methormin.
1. Pharmaceutical composition which comprises an insulin sensitivity
enhancer selected from pioglitazone or a pharmaceutically acceptable salt
thereof in combination with the insulin secretion enhancer glimepiride.
SECOND MEDICAL USE – SWISS CLAIM
Claims
1. Use of tomoxetine for the manufacture of a medicament for
treating attention-deficit/hyperactivity disorder.
Indications
STRATTERA is indicated for the treatment of AttentionDeficit/Hyperactivity Disorder (ADHD).
DOSE / USE
BONIVA Tablet 2.5 mg, 150 mg - ROCHE
Claims
1. Use of ibandronic acid of pharmaceutical acceptable salt thereof for the
manufacture of a medicament for the prevention or the treatment of disorders
characterized by pathological increased bone resorption wherein the medicament
a) comprises at least 120% of the expected efficacious daily dose, i.e. 50 – 250 mg
of ibandronic acid or a pharmaceutical acceptable salt thereof and one of more
pharmaceutical acceptable excipients thereof; and
b) the medicament is orally administered on one day per month.
USE / ADMINISTRATION METHOD
USE OF ZOLEDRONATE FOR THE MANUFACTURE OF A MEDICAMENT OF
BONE METABOLISM DISEASE
1. A method of administering 2-(imidazol-1yl)-1-hydroxyethane-1, 1-diphosphonic acid to a
patient in need of bisphosphonate treatment comprising intravenously administering
4 mg of2-(imidazol-1yl)-1-hydroxyethane-1, 1-diphosphonic acid or a pharmaceutical acceptable
salt thereof over a period of 15 minutes to a patient in need of said treatment.
Zometa
(zoledronic acid) Injection Concentrate for Intravenous Infusion
Method of Administration
Due to the risk of clinically significant deterioration in renal function, which may
progress to renal failure, single doses of Zometa should not exceed 4 mg and the
duration of infusion should be no less than 15 minutes
CASE 2: PERINDOPRIL Erbumine
SPC number: SPC/GB93/141
Maximum expiry date: 21 June 2003
Product description : Perindopril, ….. or an addition salt
obtained with a pharmaceutically compatible mineral or organic
acid, for example the tert.- butylamine salt
PERINDOPRIL PATENTS (SERVIER)
Patent No.
Coverage
1
EP 0049658 B1
Expiry date (SPC): 21.06.2003 (UK)
2
EP 1296947 B1
Alpha polymorph of perindopril erbumine
3
EP 1294689 B1
Beta polymorph of perindopril erbumine
4
EP 1296948 B1
Gamma polymorph of perindopril erbumine
5
EP 1354873 B1
Perindopril arginine (new salt)
6
EP 1032414 B1
Medical usage (perindopril and indapamide)
7
EP 1467750 B1
Orodispersible tablet
8
EP 1345605 B1
CR formulation
9
EP 0308340 B1
Process for preparing perindopril
10
EP 0308341 B1
Process for preparing perindopril
………………..
……………………………..
37
EP 1272454 B1
Process for preparing perindopril
38
EP 1268398 B1
Process for preparing perindopril
1. α crystalline form of a compound of Formula (I):
characterised by the following powder X-ray diffraction diagram, ……….
OPPOSITIONS
Quimica Sintetica
Norton Healthcare Ltd
Glenmark Pharmaceuticals Ltd
Polpharma
Hetero Drugs Limited
Ratiopharm GmbH
Krka (WITHDRAWN)
Lupin Limited (WITHDRAWN )
Niche Generics Limited (WITHDRAWN)
KRKA / SERVIER
Prenessa Tablet (Perindopril erbumine)
Country, Dosage(s)
Hungary
4MG
8MG
Poland
2MG 4MG
Slovakia
4MG
Slovenia
4MG
8MG
Czech Republic 4MG
Marketing Authorisation in UK
(mutual recognition procedure reference state: Hungary )
Launch Date
31 Oct 2005
31 Jan 2007
30 Jun 2006
31 Dec 2006
31 Jan 2006
30 Sep 2006
31 Mar 2006
May 2006
KRKA / SERVIER
Unaudited Interim Report for the Krka Company and the
Krka Group for January – September 2006
Based on the settlement the companies will withdraw all legal
actions filed against each other in various countries.
Based on settlement, Krka will market a product with the active
ingredient perindopril in alpha-crystalline form on the markets
of Slovenia, Czech Republic, Hungary, Latvia, Lithuania, Poland and
Slovakia.
APOTEX / SERVIER
APOTEX / SERVIER
Decision:
1. This is an appeal from one of the last first instance decisions of the late
Lord Justice Pumfrey. He held that Servier’s EP (UK) 1296947 was
invalid for lack of novelty and obviousness, but that if patent had been
valid, Apotex’s product would have infringed.
Perindopril tert-butyl amine polymorph patent held invalid by UK
Supreme Court (Generic Pharmaceuticals and Patents, 14 May 2008)
In the patent spat between Servier (innovator) and Apotex (Generic), UK
supreme court held the patent (EP1296947), covering crystalline polymorphic
form α of perindopril tert-butylamine salt,invalid over the prior art patents
i.e. EP0049658 * and EP0380341 **
* Basic patent
** Process patent
Perindopril Products in UK
SPC Expiry Date: 21 June 2003
Trade Name
Dosage(s)
Holder
Launch Date
Coversyl
2, 4, 8 mg
Servier
31/01/1990
31/12/2002 (8 mg)
2, 4, 8 mg
Apotex
31/08/2006
Perindopril Teva
2, 4, 8 mg
Teva
31/07/2007
Coversyl Arginine
2.5, 5, 10 mg
Servier
31/03/2008
LUPIN / SERVIER
PERINDOPRIL PROCESS PATENTS
Title
Patent No.
Applicant
PROCESS FOR PREPARATION OF
PERINDOPRIL AND SALTS THEREOF
WO-2004075889
LUPIN
NOVEL METHOD FOR PREPARATION OF
CRYSTALLINE PERINDOPRIL ERBUMINE
WO-2005037788
LUPIN
LUPIN / SERVIER
LUPIN / SERVIER
Title
Patent No.
Patent Holder
PROCESS FOR PREPARATION OF
PERINDOPRIL AND SALTS THEREOF
WO-2004075889
LUPIN
EP1603558 B1
SERVIER
NOVEL METHOD FOR PREPARATION OF
CRYSTALLINE PERINDOPRIL ERBUMINE
WO-2005037788
LUPIN
EP1675827 A1
SERVIER
LUPIN / SERVIER
• India's Lupin sells further Perindopril patent rights to
Servier for 20 mln eur *
•
MUMBAI (Thomson Financial) - India's Lupin Ltd said it has
earned 20 mln eur by selling additional patent rights of its
hypertension drug Perindopril to France-based Laboratoires
Servier.
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In April this year, Servier had reportedly bought the process
patents on the drug -- marketed in Europe as Coversyl -- for 20
mln eur, while Lupin retained other patent rights.
* Forbes.com
10.12.2007
FarmaPatent Limited
http://www.farmapatent.com.tr
Pharmaceutical Patents
Dr.Ecz. PINAR BULUT
pbulut@farmapatent.com.tr
THANKS