Acetaminophen 325 mg + Tramadol Hydrochloride 35.5 mg tablets (Ultacet): The CAFC opinion quite favorable to innovator

The Court of appeal for Federal circuit (CAFC) has reversed a portion of a previously decided summary judgment on patent litigation between innovator Ortho-McNeil ( a subsidiary of Johnson & Johnson) and Caraco (subsidiary of Sun Pharma), Teva regarding Acetaminophen 325 mg + Tramadol Hydrochloride 35.5 mg tablets (Ultracet). Further, the court has remanded the litigation to a lower court for further proceedings.

Background of the case

Prior Art: 1) Kurt Flick et al patent US3652589 published in 1972, which disclosed Tramadol and it’s combination with other analgesics. The example 23 of Flick’s patent disclosed combination of Tramadol with Acetaminophen and two other drugs.

2) Also, a German publication “WHO cancer pain guidelines” suggested various combinations of analgesics for treatment of Cancer pain.

United States district court for the district of New Jersey’s decision

Innovator Ortho claimed the combination of Tramadol + Acetaminophen in US5336691. The patentability basis as per '691 was synergistic action of both analgesics. The Tramadol is centrally acting analgesics, whereas, Acetaminophen acts by inhibiting cyclooxygenase (COX) enzyme.

Innovator got final approval to market this product on Aug 15, 2001. Afterwards due to commercial success of Ultracet, some generic players like Barr and Kali labs filed ANDA with invalidation grounds against said patent.

The example 23 of Flick’s patent has disclosed ratio of 1:10 of Tramadol + Acetaminophen. The said ratio was being covered under the scope of Ortho’s patent. Also, a German publication “WHO cancer pain guidelines” suggested various combinations of analgesics during treatment of Cancer.

Innovator in a bid to protect the patent from invalidation, filed re-examination and reissue request with USPTO to amend the disputed claims. The innovator disclosed all the references cited against the patent by generic players to examiner. Also, innovator redrafted the claims to overcome obviousness challenge of generic players. Finally, examiner reissued the US5336691 as USRE39221 after some changes.
The said reissued patent (which is listed in orange book for Ultarcet) covers:

USRE39221 (Expiry: Aug 9, 2011): The reissued claims covered a pharmaceutical composition comprising a Tramadol material and Acetaminophen, wherein the ratio of the tramadol material to acetaminophen is about 1:5.

After reissue of ‘691 as RE’221, the innovator asserted claims of ‘221 against generic players like Barr and Kali Labs. The generic players in turn filed for Summary Judgment motion of invalidity and non-infringement.

On Aug 12, 2008, the United States district court for the district of New Jersey’s Judge D.M Cavanaugh issued a summary judgment opinion and invalidated the asserted claims 43-48, 51, 54, 67, 69, 72 and 74 of ‘221 patent as obvious in the light of prior art. Also, the court invalidated the claim 6 of ‘221 patent based on prior art and found the claim to be anticipated and obvious.

Court of appeal for Federal circuit Decision
The innovator Ortho appealed against the said decision in CAFC on Aug 25, 2008.

The court observed that claims 6, 43-48, 51, 54, 67, 69, 72 and 74 covers combination of Tramadol + Acetaminophen from about 1:5 to about 1:19. A single tablet containing these two important ingredients was not disclosed in prior art.

Further, during trial, court gave importance to innovator’s expert testimony. The expert opined that Filck’s reference couldn’t obviate the said combination. Also, the interaction between Tramadol and Acetaminophen was poorly understood in 1990. The expert further opined that Flick’s broad statement that Tramadol “often” displayed synergistic action in combination with other analgesics would not be enough to obviate Tramadol + Acetaminophen ratio of about 1:5 to about 1:19. Also, expert testified that German reference teaches away from selecting the claimed combination.

Finally, the court in a 2-1 decision (panel of Judges Mayer, Prost and Moore), has remanded the litigation to United States district court for the district of New Jersey for further proceedings. The court opined that the claims 43-48, 51, 54, 67, 69, 72 and 74 of ‘221 patent are not invalid due to obviousness. Also, court has opined that claim 6 of the disputed patent is invalid due to obviousness (and not due to anticipation).

Also, the fellow Judge H.R Mayer has written dissent against said decision. As per Judge Mayer, the ‘221 patent is not novel as the said patent covers combination of two well known analgesics Tramadol and Acetaminophen”

Opinion of CAFC Here

The generic players
Following generic players have final approval for this product:

1) Barr (ANDA approved on Jul 26, 2006)

2) Caraco (ANDA approved on Dec 16, 2005)

3) Kali Labs (ANDA approved on Apr 21, 2005)

4) Mylan (ANDA approved on Sep 26, 2008)

Earlier, Innovator has settled with generic player Kali Labs (a subsidiary of Par Pharma) in July, 2007. The Kali labs have licensing agreement with innovator.

The revival of this case will certainly help innovator in blocking other generic players

Paragraph IV certification reported by USFDA (August 25, 2009)

1. Amlodipine Besylate and Atorvastatin Calcium 5 mg + 80 mg tablets (Caduet) Paragraph IV filed on April 4, 2009

2. Fluvoxamine Maleate Extended- release Capsules (Luvox CR) Paragraph IV filed for 100 mg strength on May 18, 2009 and for 150 mg strength on April 13, 2009

3. Minoxidil 5% Topical Aerosol Foam (Men’s Rogaine) Paragraph IV filed on April 6, 2009

4. Paroxetine Hydrochloride 37.5 mg Extended-release Tablets (Paxil CR) Paragraph IV filed May 19, 2009

5. Testosterone 1% Gel Metered-dose Pump (Androgel) Paragraph IV filed on December 19, 2008

(Source: USFDA website)

Montelukast (Singulair) 10 mg tablets: Court sided with innovator; generic version delayed till patent expiry (2012)

Generic pharma giant Teva Pharma (announced in a press release Here ) that the U.S. District Court for the District of New Jersey has issued a decision in its litigation over the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Merck's Singulair® (Montelukast Sodium) Tablets, holding that product patent listed in Orange Bokk is valid and enforceable. Teva is currently reviewing the Court's decision to determine its next course of action.

Earlier in a major victory for Innovator Merck, U.S. District Court for the District of New Jersey opined that Teva’s generic product would infringe plaintiff’s valid patent. The Judge ordered Teva not to make generic Singulair, and ordered the U.S. Food and Drug Administration not to approve the generic Singulair until after Merck's patent expires in 2012.

Innovator has listed following disputed patent in Orange Book for Montelukast’s (Singulair) 10 mg tablets and 4 mg granules:

US5565473 (Expiry: Aug 3, 2012): which covers unsaturated hydroxyalkylquinoline acids as leukotriene antagonists, including Montelukast as product.The said patent is a blocking patent for other generic players and is a barrier to generic entry.

Earlier, independent firm Article One Partners LLC announced that its online community found two pieces of evidence that suggest the asthma and allergy drug's key ingredient isn't novel. Law firm has alleged that innovator during prosecution of ‘473 patent has not disclosed some articles authored by Merck's scientist Dr. Robert Young (who proposed a receptor model on anti-allergic effects). Further, law firm alleged that the said article were very important for patentability determination of ‘473 patent. The same grounds were the basis for validity attack by generic player Teva. However, court was not convinced with the invalidation grounds.

Teva is first para IV filer for Montelukast tablets 10 mg/tablet. Teva filed its ANDA with para IV certification on December, 2006. Further, in May, 2009 Teva got tentative approval from USFDA for Montelukast 10 mg Tablets (Singulair) .

In March 2009, a firm that specializes in challenging the validity of patents has requested the USPTO to re-examine innovator Merck’s Orange Book listed patent US5565473 for Montelukast Tablets (Singulair). The said patent is under re-examination by USPTO.

Earlier news of IP Pharma Doc on this product Here

Gemcitabine HCl for injection (Gemzar) 200mg base/vial and 1 g base/vial: District court invalidated method of use patent

Innovator Eli Lilly announced (in a press release Here ) that the U.S. District Court for the Eastern District of Michigan has granted a motion by Sun Pharmaceuticals for partial summary judgment against key patent covering method of use of Gemcitabine HCl for injection (Gemzar) 200mg base/vial and 1 g base/vial.

The following patents are listed in Orange Book for this product:

US4808614 (Patent Expiry: Nov 15, 2010): Which covers various nucleosides like Gemcitabine as product

US5464826 (Patent Expiry: May 7, 2013): Which covers a method of treating susceptible neoplasms in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of Gemcitabine.

U.S. District Court for the Eastern District of Michigan has invalidated innovator Eli Lilly's method of use patent '826 patent. The court invalidated the said patent on the basis of obviousness type of double patenting. Innovator's coumpound patent '614 discloses use of Gemcitabine for the treatment of viral infection. Also, the said patent has disclosed use of Gemciatabine as anticancer drug. Later on, innovator got '826 patent, wherein, innovator claimed method of use of Gemcitabine for the traetment of cancer. Importantly, Sun pharma identified this important point and challenged '826 patent on double patenting grounds in the light of '614 disclosure. The court construed the claims of earlier and later patents and determined their diffrence. Finally, the court opined that claim 12 of '614 covers anticancer use of Gemcitabine and the claim 2, 6 and 7 of '826 patents have reclaimed the same use, accordingly, claims are not patentably distinct.

As per press release, innovator opined that Gemcitabine HCl for injection (Gemzar) compound patent (‘614) would remains in place until November 15, 2010, accordingly, no generic version of the drug will enter the U.S. marketplace until then.

"We strongly disagree with the Court's ruling granting summary judgment in favor of the generic challenger," said Robert A. Armitage, senior vice president and general counsel for Lilly. "We continue to believe that our Gemzar method-of-use patent is valid and will be upheld by the courts. We intend to pursue an appeal of this decision with the Court of Appeals for the Federal Circuit.

Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER): Biovail Comments on Court Ruling

Innovator Biovail Corporation announced (in a press release Here ) that the United States District Court for the District of Delaware, Honorable Judge Kent A. Jordan has issued an opinion in favour of generic player Par Pharmaceuticals in the patent-infringement litigation relating to Tramadol hydrochloride 100mg and 200mg ER tablets (Ultram ER). Although Biovail is not a party to the action, the decision could have an effect on Biovail’s revenues relating to Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER).

The following patents are listed in Orange Book for Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER):

US6254887 (Assignee: Euro-Celtique S.A ; Expiry: May 10, 2014): The patent covers A controlled release oral pharmaceutical preparation suitable for dosing every 24 hours comprising a substrate comprising a pharmaceutically effective amount of tramadol or a salt thereof; said substrate coated with a controlled release coating; said preparation having a dissolution rate in vitro when measured using the Ph. Eur. Paddle Method at 100 rpm in 900 ml 0,1 N hydrochloric acid at 37.degree. C. and using UV detection at 270 nm, between 0 and 50% tramadol released after 1 hour; between 0 and 75% tramadol released after 2 hours; between 3 and 95% tramadol released after 4 hours; between 10 and 100% tramadol released after 8 hours; between 20 and 100% tramadol released after 12 hours; between 30 and 100% tramadol released after 16 hours; between 50 and 100% tramadol released after 24 hours; and greater than 80% tramadol released after 36 hours, by weight, said preparation providing a therapeutic effect for about 24 hours after oral administration.

US7074430 (Assignee: Euro-Celtique S.A ; Expiry: May 10, 2014): The patent covers a solid controlled release oral dosage form, comprising, a therapeutically effective amount of tramadol or a pharmaceutically acceptable salt thereof incorporated into a normal release matrix, said matrix overcoated with a controlled release coating comprising a polymethacrylate or a water insoluble cellulose, said dosage form providing a therapeutic effect for at least about 24 hours.

The holder of the patent Purdue Pharma (and partners like Biovail, Napp and ORTHO-McNEIL) were in litigation with generic player Par for this product in United States District Court for the District of Delaware since 2007.

The court opined that disputed claims 3, 13, 27 and 29 of ‘887 patent and claims 5, 7 and11 of ‘430 patents are infringed by Par’s generic product. However, the disputed claims are invalid and obvious in the light of Oshlak (US5580578) disclosure (alone) and Oshlak in combination with Kaiko (US5478577), Lintz and Stewart Leslie (one of the co-inventor of disputed patents) article entitled “Continues controlled release formulations”. The court further opined that the prior art clearly suggets that it would have been obvious for the formulator to develop controlled release formulation of the Tramadol with the use of excipients and formulation techniques available for person having ordinary skilled in the art. At the time of development of purdue’s formulation, the controlled release formulation of related compunds like Hydromorphone, Oxycodone, Dihydrocodeine, Codeine and Morphine were known. Also, controlled relese techniques and excipients were known as per Merck/Bondi patent EP147780. Importnatly, Judge concluded that the claimed invention is obvious both under pre KSR and Post KSR obviousness analysis.

Further, Judge rejected Par’s inequitable conduct charges (during prosecution of disputed patents with USPTO) against innovator Purdue and opined that patents is not invalid due to inequitable conduct.

The Court’s ruling, in conjunction with Par’s recent receipt of tentative approval from the U.S. Food and Drug Administration (FDA) for its 100mg and 200mg strength tablets, could allow Par to launch their generic formulation of those tablet strengths at any time. The generic player Par has not got final approval on 300 mg strength. Biovail will be consulting with its partner, Pricara (a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) to determine next steps. The decision as to whether or not to appeal the decision lies with Purdue Pharma LP, the patent holder.

Biovail recorded Ultram® ER revenues of $81.9 million in 2008, and $37.2 million in the first half of 2009.

Update

Labopharm comments on judgment in Purdue patent litigation

Labopharm has commented on this litigation ( in a press release Here). In his decision, Circuit Judge Kent Jordan entered judgment in favor of Purdue and against Par on the issue of infringement and rejected Par's claim that the patents were unenforceable for inequitable conduct. Judge Jordan, however, entered judgment in favor of Par and against Purdue on the issue of validity, citing obviousness.

This judgment could permit Par to market its generic formulation of Ultram ER in the U.S., should it receive final regulatory approval from the U.S. Food and Drug Administration. Although Labopharm is not a party to this action, if Par was to launch its generic formulation of Ultram ER, it could impact U.S. sales of Labopharm's own once-daily tramadol product, Ryzolt(TM), which is marketed in the U.S. by Purdue. Ultram ER, and therefore any generic version of it, is not A/B rated to Ryzolt, meaning it cannot be substituted for Ryzolt at the pharmacy. Labopharm is currently in discussions with Purdue to evaluate next steps in this matter, including a potential appeal of the decision.

Tacrolimus (Prograf) 0.5 mg, 1mg and 5 mg capsules: District Court refused to block generic version

Innovator Astellas announced (in a press release Here ) that U.S. District Court in Washington, D.C has refused preliminary injunction and temporary restraining order against USFDA’s approval of ANDA for Tacrolimus (Prograf) 0.5 mg, 1mg and 5 mg capsules.

Earlier, innovator informed about Citizen petition refusal by USFDA (in press release Here ). Subsequently, innovator challenged USFDA’s decision (as reported in the press release Here ) and filed a complaint in U.S. District Court in Washington, D.C. and requested the court to issue a preliminary injunction and temporary restraining order against USFDA’s approval of ANDA for Tacrolimus (Prograf) 0.5 mg, 1mg and 5 mg capsules.

As reported earlier by IP Pharm Doc Here, the product patent US4894366 expired on April 8, 2008. However, generic version were not approved immediately after the expiry of product patent, as innovator filed citizen petition against the generic approval.

Earlier, Innovator got final approval for 1 mg and 5 mg capsules on Apr 8, 1994 and for 0.5 mg capsules on Aug 24, 1998 for use of Tacrolimus (Prograf) in liver and kidney transplants.

Also, innovator secured Orphan Drug Exclusivity (ODE) in 2006 for new clinical indication, to prevent rejection of heart transplants. As per USFDA database, the said exclusivity would expire on March 29, 2013.

Sumatriptan Succinate 25, 40 and 100 mg tablets (Imitrex): More generic players got final approvals

The following generic players have got final/tentative approval to market antimigraine formulation Sumatriptan Succinate 25, 40 and 100 mg tablets (generic version of Imitrex):

Final approvals

1. TEVA (ANDA approved on February 9, 2009)
2. RANBAXY (25 and 50 mg tablets on August 10, 2009; 100 mg on February 9, 2009)
3. DR REDDYS LABS INC (ANDA approved on August 10, 2009)
4. COBALT LABS INC (ANDA approved on August 10, 2009)
5. SANDOZ (ANDA approved on August 10, 2009)
6. ROXANE (ANDA approved on August 10, 2009)
7. ORCHID HLTHCARE (ANDA approved on August 10, 2009)
8. SUN PHARM INDS (ANDA approved on August 10, 2009)
9. AUROBINDO PHARMA (ANDA approved on August 10, 2009)
10. MYLAN (ANDA approved on August 10, 2009)

Tentative approvals

1. GENPHARM (January 24, 2007)
2. WATSON LABS (August 27, 2007)

Most of generic players got final approval on August 10, 2009.

Tacrolimus (Prograf) 0.5 mg, 1mg and 5 mg capsules: Sandoz launched first generic in US

Generic player Sandoz has announced the introduction of Tacrolimus 0.5 mg, 1mg and 5 mg capsules, a generic equivalent of Prograf, in the US market. Tacrolimus is an immunosuppressive treatment used to help prevent rejection of a kidney or liver transplant.

Sandoz is the first and only company to launch generic Tacrolimus in the US, delivering on its strategy of being first-to-market with key products. With the introduction of Tacrolimus, Sandoz is expanding patient access to cost-saving transplant treatment options in the US.

Sandoz got final approval to market this product on Aug 10, 2009.

The product patent US4894366 expired on April 8, 2008. However, generics were not launched immediately after the expiry of product patent, as innovator filed citizen petition against the generic approval.

Innovator Astelles challenged USFDA’s bioequivalence protocol for the generic manufacturer. Further, innovator highlighted the importance of parameters for generic switch for physicians.

Importantly, USFDA denied citizen petition of innovator, which facilitated the generic approval process. As per USFDA, the current ANDA review process to establish quality safety and efficacy is adequate to establish interchangeability of innovator drug with generic version of Tacrolimus.

Earlier, innovator got approval to market this product on 1mg and 5 mg capsules on Apr 8, 1994 and 0.5 mg capsules on Aug 24, 1998

Desloratadine 5 mg Tablets (Clarinex): Orchid Chemicals and Schering-Plough settled patent lawsuits

Generic player Orchid and innovator Schering-Plough (now, subsidiary of Merck) have settled the patent litigation relating to Desloratadine tablets, 5 mg and Desloratadine 2.5 mg and 5 mg orally disintegrating tablets (ODT).

These are generic versions of Schering's Clarinex and Clarinex Reditabs for allergy medication. The litigation has been pending in the US, District Court of New Jersey since September 2006.

Pursuant to the settlement, Orchid will have the right to market desloratadine tablets 5mg and desloratadin 2.5 mg and 5 mg orally disintegrating tablets in the US from July 1, 2012 and January 1, 2012 respectively after approvals from US FDA. Orchid's products may be the prescription form or over-the-counter version products depending on the status of Clarinex and Clarinex Reditabs at the time.

Additional terms of the settlement are confidential, and the agreement is subject to review by the Department of Justice and the Federal Trade Commission.

Earlier, innovator had sued various generic players like Zydus, Sandoz, Mylan, Orchid, Perrigo, Glenmark, GeoPharma, Lupin, Ranbaxy, Sun, Watson, Dr. Reddy's who filed ANDA to market this product. Importantly, Innovator has patents listed in orange Book with expiries in 2020.

Apart from Mylan, innovator had settled with Geopharm, Perrigo, Watson Pharma and Ranbaxy, Dr. Reddy, Lupin.

Possibly, all generic players are in licensing agreement with Innovator and would launch generic around July, 2012.

New Para IV Filings reported by USFDA on Aug 3, 2008

1. Solifenacin Succinate Tablets (Vesicare) Para IV filed on April 8, 2009

2. Dexmedetomidine Injection (Precedex) 100 mcg/mL Para IV filed on April 8, 2009

3. Quetiapine Fumarate Extended-release Tablets 150 mg (Seroquel XR) Nov 17, 2008

(Source: USFDA)

Paragraph IV filings reported by USFDA (June-July, 2009)

1. Candesartan Cilexetil and Hydrochlorothiazide (Atacand HCT) Tablets 32 mg+25 mg Paragraph IV filed on March 6, 2009 (Earlier, a generic company has filed Paragraph IV against Atacand HCT Tablets 16 mg+12.5mg and 32mg+12.5mg on June 25, 2008)

2. Diazepam (Diastat Acudia) Rectal Gel 5 mg/ml, 4mL pre-filled syringe Paragraph IV filed on Dec 8, 2008 and for 2mL pre-filled syringe on Dec 23, 2008

3. Mycophenolic acid (Myfortic) Delayed-release Tablets 360 mg Paragraph IV filed on Feb 2, 2009

4. Telmisartan and Hydrochlorothiazide (Micardis HCT) Tablets 80 mg/12.5 mg and 80 mg/25 mg Paragraph IV filed on Dec 31, 2008

5. Vardenafil hydrochloride (Levitra) Tablets 20 mg Paragraph IV filed on March 5, 2009

6. Doxercalciferol Capsules (Hectorol) 0.5 mcg and 2.5 mcg Paragraph IV filed on March 25, 2009

7. Atovaquone and Proguanil Hydrochloride 250/100 mg tablets Para IV filed on April 3, 2009

9. Efavirenz (Sustiva) 600 mg tablets Para IV filed on April 9, 2009

Olmesartan (Benicar), Olmesartan+Hydrochlorthiazide (Benicar HCT) and Olmesartan+ Amlodipine (AZOR) formulations: Court upheld the validity of Key pat

Innovator company Daiichi Sankyo announced (in a press release Here) that the U.S. District Court in New Jersey has issued a decision in our U.S. patent litigation against Mylan (and its subsidiary Matrix) upholding the validity of our patent covering the Olmesartan (Benicar), Olmesartan+Hydrochlorthiazide (Benicar HCT) and Olmesartan+ Amlodipine (AZOR) formulations. Mylan was the first company to file ANDA application with a Paragraph IV certification against key patent covering Olmesartan and combinations. Subsequently, Innovator sued Mylan in New Jersey district court for the infringement of following key patent:

US5616599 (Expiry: Apr 25, 2016): The claim 13 covers Olmesartan Medoxomil as product (which was at issue during trial)

Mylan tried to invalidate the disputed patent based on obviousness grounds. Mylan alleged that Olmesartan is obvious in the light of Dupont company’s patent US5138069 and US5137902, which have priority over '599 patent.

Olmesartan is a structural analogue of Losartan and differ at two positions of imidazole ring. The 4-position of imidazole ring in losartan has chloro group (lipophilic group) whereas, Olmesartan has hydroxy propyl group (hydrophilic group), and in Losartan 5-position of imidazole ring has hydroxy methyl group, whereas, Olmesartan has carboxy group.

Importantly, the prior art teaches away from using hydrophilic group group at position-4 of imidazole ring, as said change resulted in lower activity. Also, formation of Medoxomil ester at 5-position of imidazole ring was not obvious to skilled person. Additionally, court considered commercial success of Olmesartan.

Based on above factors, court opined that Mylan failed to prove obviousness by clear and convincing evidence against ‘599 patent and concluded that disputed patent is neither invalid nor unenforceable.

Olmesartan medoxomil, an active ingredient in Benicar®, Benicar HCT® and AZOR®, is an angiotensin II receptor antagonist that Daiichi Sankyo independently developed, and is marketed in over 50 countries as an antihypertensive drug which suppresses vasoconstriction by affecting the rennin-angiotensin system to control blood pressure.

Drospirenone and Ethinyl estradiol (Yasmin) 3.0 mg+0.03 mg tablets: CAFC invalidated key patent

Generic pharma giant Teva Pharma announced (in a press release Here ) that U.S. Court of Appeals for the Federal Circuit has affirmed a ruling by the U.S. District Court for the District of New Jersey (as reported by us Here ) has declared innovator Bayer's orange book listed patent for Drospirenone and Ethinyl estradiol (Yasmin) 3.0 mg+0.03 mg tablets.

The CAFC has declared following key patent covering Yasmin as invalid:

US6787531 (Expiry: AUG 31, 2020): Which covers combination of Drospirenone and Ethinyl estradiol (Micronization technique)

Barr argued that micronization technique is obvious as it increases dissolution of Drospirenone. Bayer argued that micronization without coating to reduce acid degradation in stomach is not obvious. Court decided in the light of KSR V/S Teleflex decision and concluded that person having ordinary skilled in the art would have known to test bioavailability of Drospirenone, and when choosing from finite number of methods for delivering oral contraceptive, micronized tablets without enteric coated would have been obvious to try.

Court also observed that Spirorenone (Drospirenone is a metabolite of Spirorenone) and Spirorenone have similar features and there is reasonable expectation of success on this parameter that both compounds perform similarly if not identically. Further, obviousness does not require absolute predictability of success but all that is required is reasonable expectation of success. The Krause articles rightly obviate Drospirenone micronization technique.

Earlier on June 24, 2008, Barr Laboratories, Inc. (now a wholly owned subsidiary of Teva Pharmaceutical Industries, Ltd.) announced that it had entered into a supply and licensing agreement with Bayer for distribution of a generic version of Yasmin®. Under the terms of that agreement, Bayer supplies Barr with the generic product, which Barr distributes in the U.S. under the Barr Laboratories label, Ocella. Ocella was launched in July, 2008 and had annual sales of approximately $170.2M in the United States for the twelve months that ended December 31, 2008, based on IMS sales data.

Opinion of CAFC Here

Amifostine (Ethyol) 500 mg/vial injection (Ethyol): Sun Pharma (Caraco) announced settlement with innovator

Indian Pharma giant Sun Pharma (announced in a press release Here ) that its subsidiary
Caraco Pharma (announced in a press release Here ) has executed a settlement agreement with innovator MedImmune, stipulating the dismissal of the lawsuits filed in the United States District Court for the District of Maryland regarding the submission of an Abbreviated New Drug Application (ANDA) for a generic version of Amifostine (Ethyol) 500 mg/vial injection (Ethyol) .

Under the settlement agreement, MedImmune grants Caraco a license to certain patents, permitting Caraco to continue marketing a generic version of Ethyol in the United States. The settlement resolves the entirety of the litigations between the parties.

The following patents are listed in Orange Book for this product:

US5424471 (Expiry: July 31, 2012): Covers crystalline Amifostine composition

US5591731 (Expiry: July 31, 2012): Covers crystalline Amifostine composition with improved stability

US5994409 (Expiry: Dec 8, 2017): Method of use

Before settlement, both companies were in litigation (since 2004) on above patents in the United States District Court for the District of Maryland

Amifostine which is chemically, S-2-(3-Aminopropylamino) ethyl dihydrogen phosphorothioate (Ethyol) is used as an adjuvant in cancer treatment.

Earlier, Caraco got final approval from USFDA to market Amifostine (Ethyol) 500 mg/vial injection in March, 2008.

Dexmedetomidine hydrochloride 100 mcg base/ml injection (Precedex): Orion Corporation confirmed receipt of Para IV letter from Sandoz

Innovator Orion Corporation has confirmed (in a press release Here) that generic player Sandoz has filed ANDA with Paragarph IV certification against Orange Book listed patents for Dexmedetomidine hydrochloride 100 mcg base/ml (Precedex) injection.

following Orange Book listed patents for Dexmedetomidine hydrochloride 100 mcg base/ml (Precedex) injection:

US5344840 (Expiry: Sep 6, 2011): Which covers a method of perioperative treatment of mammals to reduce the responses of the autonomic nervous system to stressful stimuli during an operation by administering to said mammal in whom such reduction is desired an effective amount of dextro 4-[1-(2,3-dimethylpheny)-ethyl] -1H-imidazole or a non-toxic pharmaceutically acceptable salt thereof substantially in the absence of the laevo form of said compound.

US4910214 (Expiry: Jul 15, 2013): which covers The d enantiomer of medetomidine or a non-toxic pharmaceutically acceptable acid addition salt thereof.

US6716867(Expiry: Mar 31, 2019) : Which covers a method of sedating a patient in an intensive care unit, which comprises administering to the patient an effective amount of dexmedetomidine of a pharmaceutically acceptable salt thereof, wherein the patient remains arousable and orientated.

The generic player Sandoz's has challenged ‘214 and ‘876 patent.

The USFDA approved NDA for this product on Dec 17, 1999

Loestrin 24 Fe and Femcon Fe: Innovator Warner confirmed patent challenge by Lupin

Innovator Warner Chilcott Limited announced (announced in a press release Here) that it has received two Paragraph IV Certification Notices from Indian generic player Lupin. The Paragraph IV Certification Notices advise the Company of the filing of Abbreviated New Drug Applications (ANDAs) by Lupin for generic versions of the Company's oral contraceptives Loestrin 24 Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets) and Femcon Fe (norethindrone, ethinyl estradiol tablets, chewable, ferrous fumarate tablets)

Loestrin 24 Fe, which was launched in March of 2006, is protected by US5552394 which expires in 2014.

Femcon Fe, which was introduced by the Company during the second half of 2006, is protected by US6,667,050 which expires in 2019.

Earlier, innovator settled it’s pending litigation with Watson as reported by us Here