Disputes: Pharma Sector

Arindam Sen

Metabolite Labs. Inc. v. Lab Corp. (June 2004)

• Patent Process:– Researchers at the University Patents Inc. (UPI) - discovered a

relationship between elevated levels of total homocysteine and a deficiency in either cobalamin or Folate & developed a test to identify the deficient vitamin using methylmalonic acid (the panel test method). The patent claims both the total homocysteine test and the total homocysteine-methylmalonic acid test.

– The Successor of UPI i.e. Competitive Technologies licensed this technology to Metabolite Laboratories

– Metabolite Laboratories sub licensed it to Roche Biomedical Lab (now Lab Corp)

• Dispute:– Lab Corp started using the test for examination of Homocysteine

developed by Abbott laboratories and discontinued the payment of Royalty to Metabolite Laboratories

– Metabolite sued the Lab Corp for Indirect Infringement as well as the Breach of Contract

•Lab Corp argued – the dictionary meaning of word “correlating” is “to establish a mutual or

reciprocal relation of” an elevated level of homocysteine. – “correlating” step as establishing that an elevated level of

homocysteine is caused by a “shortage of cobalamin which causes a hematologic or neuropyschiatric abnormality,” or “[a] deficiency of folate, which causes a hematologic abnormality.”

•The Court accepted the dictionary definition given by the Lab Corp but declined to “include a reference to hematologic or neuropsychiatric abnormality”•LabCorp urged the district court to define “correlating” to include either a mutual or a reciprocal relationship. In the damages calculation, however, LabCorp prefers to restrict the claim to correlations that yield mutual relationships while excluding any reciprocal relationships. •Decision: -The Court held LabCorp partially breached its contract with Metabolite. Based on this verdict, the district court assessed damages of $3,652,724.61 for breach of contract and $1,019,365.01 for indirect infringement.

Knoll Pharmaceutical Company, Inc.

The John and Lois Arnold Family Limited Liability

Partnership. V.

Teva Pharmaceuticals USA, IncMay 2004

Obviousness in claims

• The Patent: Knoll Pharmaceutical claimed a Patent, which is directed to methods and compositions for treating pain by administering a combination of hydrocodone and ibuprofen in specified amounts

• 1997: Knoll received FDA approval to market tablet containing 7.5 mg of hydrocodone bitartrate and 200 mg of ibuprofen

• 2000: Teva Pharma filed an Abbreviated New Drug Application (“ANDA”), in accordance with Hatch-Waxman Act seeking authorization to market tablet containing 7.5 mg of hydrocodone bitartrate and 200 mg of ibuprofen

• Dispute:– Knoll against this brought a suit for the infringement – Lower court: Rejected Knoll’s Patent for obviousness– Federal court: prior art appears to suggest combining an opioid,

such as hydrocodone, with various NSAIDs, such as ibuprofen but no records of enhanced efficacy

• Knoll submitted additional data directed to similar showings of efficacy

• “There is no requirement that an invention’s properties and advantages were fully known before the Patent application is filed, or that the Patent application contains all the work done in studying the invention, in order for that work to be introduced into evidence in response of litigation attack. Nor is it improper to conduct additional experiments and provide later-obtained data in support of Patent validity”

• Decision:-– The case was decided in favor of Knoll

Pharmaceutical by overturning the decision of District court, which was claiming the Knoll patent to be obvious.

In re John Ngai

May 2004

Anticipation through prior art

• Ngai invented a new method for amplifying and normalizing RNA.

• Application for patent:– application contained 20 claims – Claims 1-18: Method of amplifying - accepted– rejected claims 19 and 20 as unpatentable – The Board reversed the rejection with respect to claim

20 – rejection of claim 19 as anticipated by prior art

• Ngai: appealed to court for claim 19• Ngai: addition of new printed matter to a known

product makes the product patentable (?)• PTO: Ngai can claim the new use as a method,

but he cannot claim the existing product itself

Decision

• The Federal Circuit upheld a USPTO decision that Ngai’s patent claim is anticipated by the prior art.

• The USPTO allowed Ngai claims for a new method of extracting ribonucleic acids (“RNA”). – The agency rejected a dependent claim that recited a kit for

extracting RNA including a premeasured portion of a buffer and “instructions describing the method of claim 1.” The only difference between prior art kits and the claim was the content of the instructions.

• “If we were to adopt Ngai’s position, anyone could continue patenting a product indefinitely provided that they add a new instruction sheet to the product.”

Housey Pharmaceuticals, Inc., V.

Astrazenca UK Ltd.,Astrazenca LP, Astrazenca

Pharmaceuticals LP.May 2004

Interpretation of the Claim to decide the scope of the Patent.

• Patent: Housey Pharmaceuticals - owner of four patented techniques with the name “Methods of Screening for Protein Inhibitors or Activators” – assay, or test, to determine whether a substance, often a

candidate for a pharmaceutical product or drug, is an “inhibitor or activator” of a particular protein (the “protein of interest” or “POI”) in a cell

• Housey then filed a suit against Astrazenca UK Ltd., Astrazenca LP and others on the basis of alleged infringement of his four patented methods

• Core issue: interpretation of “inhibitor/activator”• Housey

– “inhibitor or activator of a protein," which was held to mean "a substance that has a greater effect on the phenotype of cells that express the protein of interest at a higher level than on the phenotype of cells that express the protein of interest at a lower level or not at all.”

– Housey argued for a limited direct binding concept

Decision

• District & Federal court – rejected Housey’s arguments– Plain & ordinary meaning of claim language unless

otherwise stated• But, what about technical interpretation differing

from plain dictionary meaning?• Decision:

– the majority panel members interpreted the term “inhibitor or activator of a protein” broadly to encompass substances that inhibit or activate without binding to the protein, as well as substances that bind to it. The interpretation furnished the claims invalid, according to a condition by the parties.

Elan Corporation, PlcV.

Andrx Pharmaceuticals, Inc.May 2004

Whether a Letter can be an official License?

• Sodium salt of (S)-6-methoxy-α-methyl-2-naphthyleneacetic acid, commonly known as “naproxen sodium,” NSAID: expiry date of that Patent was on 21st December 1993

• Elan was preparing to develop a controlled-release naproxen formulation for once-daily administration – filed a patent

• August 7, 1987, Kenneth E. McVey, Elan’s Executive Vice President for Business Planning and Commercial Development, wrote a letter to K. Michael Forrest, Vice President of Lederle Laboratories regarding the preparation and about the future plan for the licensing of the said drug

• Lederle Laboratories took that letter as an offer to license and a suit was filed

• Letter to Lederle – initial inquiry & lacked the hallmarks of a commercial offer, such as mention of prices, quantities, time and place of delivery, and product specifications beyond the general statement that the potential product would be a 500 mg once-daily tablet containing naproxen

• Decision: the case was decided in the favor of Elan and the letter was not termed as the license to drug

Steven v. Tamai

May 2004

Error in language translation

• Patent:– Stevens's involved U.S. Patent No. 5,393,368 ("the '368 patent")

was filed February 7, 1994, and issued February 28, 1995 – Tamai's involved Application No. 08/196,839 ("the '839

application") was filed February 15, 1994. The '839 application is a continuation-in-part of U.S. Patent Application No. 08/030,183 ("the '183 application"), which was filed March 29, 1993

– On the basis of the March 29, 1993 filing date, Tamai was accorded senior party status.

• Steven’s motion: several European applications showing a constructive reduction to practice as early as February 10, 1993

• Tamai's motion was based on Japanese Patent Application No. 3-68371 ("the Japanese '371 application") and PCT Application No. PCT/JP92/00947 ("the PCT '947 application"). Both applications are in Japanese.

• Steven opposed the motion as no copies of Japanese & PCT applications & their translation served

• Tamai did not include an English language translation of the PCT '947 application and an affidavit attesting to the accuracy of the translation

• Decision: -– Thus the decision was agreed to the view of USPTO and held

that Tamai is not entitled to have the date of Japanese language PCT application, as Tamai has not fulfilled the requirement of English language translation of that application and thus Tamai canot be claimed as the first inventor.

Novartis Pharmaceuticals Corporation, V.

Eon Labs Manufacturing, Inc.,

April 2004 Whether Infringement can be claimed when the

drug is Ingested by the Patient inside the Stomach

• Novartis: Patent on a formulation of administering cyclosporin (an immuno-suppressant) as hydrosol

• Novartis filed a suit against Eon for indirect infringement• Eon: manufactures capsules that contain cyclosporin

dissolved in a small amount of ethanol – inside human body forms hydrosol when the capsule mixes with

the aqueous environment of the user’s stomach

• The Federal Circuit relied on dictionary definitions to conclude the term is limited to an aqueous medicinal preparation prepared outside the body

• Decision against Novartis

Chiron CorporationV.

Genentech, IncApril 2004

a) Lack of written description. b) Enablement Requirement

• Early 1980s: scientists at Chiron’s predecessor corporation, Cetus Corp. began investigating monoclonal antibodies that target human breast cancer antigens (the antibody eventually termed HER2)

• Patent:• The inventors filed their first application on February 8, 1984. • Within a year, on January 11, 1985, they filed a continuation-in-part

(CIP) application claiming priority based on that first 1984 application.

• The inventors filed another CIP application on May 21, 1986. • Eventually, the application that led to the said patent was filed as

another CIP on June 7, 1995.

• When the patent issued, Chiron sued Genentech over sales of Herceptin®, a humanized antibody useful for the long-term treatment of breast cancer. Herceptin binds to the HER2 antigen and thus inhibits the growth of cancerous cells

• Issue: the antibodies mentioned in the Application were not existed at the time of filing of application thus a written description was required in the specification

• Decision:– The Court held that the antibodies claimed by the Plaintiff under

the Application of 1984,85 and 86 are invalid. As in 1984 the murine antibodies does not exist and thus the written description was not provided. In 1985,86 application the antibodies required undue experimentation which lacks with the quality of Enablement Requirement

Arnold Partnership v. Dudas

March 2004

Extension of Patent Term

• The Arnold Partnership (Arnold) is the owner of record for the patent, which claims compositions comprising hydrocodone (or a salt thereof) and ibuprofen (or a salt thereof) as well as methods of treating pain with those compositions. The said patent was filed on December 18, 1984, was issued on May 6, 1986, and is due to expire on December 18, 2004

• On November 20, 1997, Arnold filed an application with the PTO for patent term restoration

• PTO denied: Vicoprofen did not comply with the “first commercial marketing” requirement – “To extend the term of a patent claiming a composition

comprising A and B, either A or B must not have been previously marketed.”

• FDA interpretation Vs PTO interpretation

Bristol-Myers Squibb Company, V.

Pharmachemie B.V.

March 2004

Double Patenting

• Patents:– the ’927 patent: Research Corporation Technologies, Inc., is the owner

& Bristol-Myers Squibb Co. is the exclusive licensee – the ’707 patent: issued in 1979 and expired in 1998

• Appellant Pharmachemie, B.V., filed an Abbreviated New Drug Application (“ANDA”) with the Food and Drug Administration, seeking FDA approval to market a cancer-treating drug covered by the ’927 patent.

• RCT & BMS brought suit against APBV• the ’989 application” of ‘927 patent, disclosed and claimed

compounds corresponding generally to the compounds that were ultimately claimed in the ’707 patent. In addition, the ’989 application claimed methods of treatment and compositions corresponding to the claims that were ultimately included in the ’927 patent

• In the course of the prosecution of the ’989 application, the examiners imposed two restriction requirements. The first, imposed in 1973, required that the applicants elect either the compound claims, classified in art class 260, or the method of treatment and composition claims, classified in art class 424.

• In addition, the 1973 restriction requirement directed the applicants to elect “a single disclosed species for examination on the merits.” – As a result of the 1973 restriction requirement, the applicants

elected the compound claims and withdrew the non-elected method of use and composition claims from further consideration at that time.

• The examiner then rejected the elected compound claims on the basis of lack of utility.

• Decision: -• The Federal Circuit decided Bristol is not

protected against a double patenting charge by Patent Act section 121, which prohibits use of double patenting as a ground for invalidity after the USPTO has made a “restriction” requirement. An earlier restriction requirement was no longer in effect by the time Bristol filed the application that issued as the patent.

Pfizer Inc., V.

Dr. Reddy's Laboratories, Ltd.And Dr. Reddy's Laboratories,

Inc.,February 2004

Indirect Infringement by changing the Salt

• Patent: – Pfizer owned a Patent on amlodipine and its salts, amlodipine

besylate and amlodipine maleate– 17 year term of protection for the said Patent was ending on

February 25,2003 but it was extended for 1,252 days i.e. till July 31,2006 due to the extra time consumed by Federal regulatory approval process, as authorized by the Drug Price Competition and Patent Term Restoration Act of 1984, (the Hatch Waxman Act)

• In Pfizer’s Application to PTO requesting term extension Pfizer identified Norvasc® as the product for which regulatory approval had been obtained, and stated that Norvasc® was “further identified” as amlodipine besylate

• December 2001: Dr. Reddy’s filed a new drug application, known as a “paper NDA”, proposing to market amlodipine maleate salt – the term extension applies only to the besylate salt because that

is the registered product • Decision: the Federal Circuit held simply changing the

salt does not defeat the patent extension.

Ranbaxy Pharmaceuticals, Inc.and Ranbaxy Laboratories

Limited, V.

Apotex, Inc.

December 2003Redrafting of Dependent claim as Independent one

• Patent: Apotex is the owner of Patent directed to a process for preparing amorphous cefuroxime axetil using formic acid

• FDA approved Ranbaxy’s Abbreviated New Drug application to launch its cefuroxime axetil product using acetic acid

• Ranbaxy sought a declaratory judgment that it does not infringe the claims of the said patent of Apotex.

• Apotex filed a counterclaim that Ranbaxy infringes and moved for a preliminary injunction – Ranbaxy infringed under the doctrine of equivalents & formic

acid & acetic acid are equivalents• Acetic acid not claimed as solvent by Apotex in its patent

application - Apotex’s argument that the acetic acid solvent equivalent used by Ranbaxy would not have been foreseeable

• The court denied the motion and also found that Apotex had failed to establish irreparable harm, that the balance of hardships weighed against equitable relief, and that an injunction was not in the public interest

The University of Colorado Foundation Inc.

v. American Cyanamid Co.

September 2003 Infringement through Copying of Original

manuscript (Stolen Invention)

• Cyanamid’s Lederle Laboratories manufactures and markets Materna 1.60 (“Materna”), a prenatal multivitamin/mineral supplement containing 60 mg of iron

• In 1979, Stuart Pharmaceutical, the manufacturer of a competing prenatal supplement Stuartnatal 1+1 (“Stuartnatal”), began advertising that its product provided superior iron absorption to that of Materna

• Dr. Ellenbogen (a Cynamide employee) asked his friend and long-time professional colleague, Dr. Allen to conduct studies

• Dr. Allen together with his colleague Dr. Seligman, a hematologist and professor of medicine at the University of Colorado Health Sciences Center, conducted the comparison studies (I, IA, II, IIA) in 1979-80– revealed that there was an inhibitory “threshold effect with calcium

carbonate” and determined the specific levels of calcium carbonate and magnesium oxide at which the inhibitory effect occurs

• Study III: concluded that the reduction in calcium carbonate in the Reformulation B improved iron absorption to 5.0 mg, which was greater than the 3.5 mg recommended for pregnant women

• Another study (“Study IV”) comparing the absorption of iron alone with the absorption of iron from reformulated Materna, Stuartnatal, and two other competing prenatal multivitamin/mineral supplements (March, 1981)

• Results sent for publication in New England Journal of Medicine & confidential copy to Dr. Ellenbogen

• Without informing the Doctors or the University, Cyanamid filed a patent application in December of 1981, claiming exclusive rights to the reformulation and naming Dr. Ellenbogen as its sole inventor – The '634 patent issued from this application in 1984

• The Doctors & the University filed an action against Cyanamid asserting claims for fraudulent nondisclosure, unjust enrichment, and equitable remedy under the federal patent laws

• The Federal Circuit upheld a judgment requiring Cyanamid to pay more than $50 million damages and interest

• ruled the doctors were the sole inventors

University of West VirginiaV.

Van Voorhies

September 2003Ownership over the Second

Generation Invention by Student

• The Federal Court held that the Lower Court has erred in ordering Vanvoorhies, a former doctoral student to transfer its second generation patents over toroidal, helical antennas to the University. In an earlier appeal the federal court held that the university could claim Patent over the first generation patents. But on the basis of that judgment Lower court held that the University could claim ownership over second-generation patents. But if the second generations Patent, which are issued from the application, which were not reissue or not based on the continuing application of first generation patents. Thus the Ownership over the Second Generation was not decided.

GLAXO WELLCOME INC.,V.

ANDRX PHARMACEUTICALS, INC.,

September 2003Infringement & Claim Construction

• Wellbutrin SR & Zyban - active ingredient of both products is bupropion hydrochloride & belong to Glaxo

• Andrx filed two Abbreviated New Drug Applications (ANDA) seeking approval of generic counterparts of the Glaxo sustained release products, asserting identity of active ingredient and properties with those of WellbutrinSR and Zyban. – Andrx also filed a submission stating that its product will not

infringe the Glaxo’s patent

• The issues of claim construction and infringement focused on the controlled release agent, hydroxypropyl methyl cellulose (HPMC)

• The Federal Court concludes that the claims are not limited to a specific grade of hydroxypropyl methylcellulose as used in admixture with the bupropion– Decided in favor of Glaxo