Escolar Documentos
Profissional Documentos
Cultura Documentos
Turmeric
Patents Granted on TM
The grant of patents linked to indigenous knowledge of the developing world needs to be addressed jointly by the developing and developed world. A recent study by an Indian expert group
examined randomly selected 762 US patents which were granted under A61K35/78 Out of these patents, 374 patents were found to be based on traditional knowledge
The governments in the Third World, as well as members of the public, are rightly concerned about the grant of patents for nonoriginal inventions in the traditional knowledge systems of the developing world.
Observations:
The turmeric case was a landmark case as it was the first time that a patent based on the traditional knowledge of a developing country had been successfully challenged. The legal costs: US $10,000 ( Govt. of India)
Neem
In 1994 the EPO granted patent No. 0436257 to the US Corporation W.R. Grace and USDA for a method for controlling fungi on plants by the aid of a hydrophobic extracted neem oil. In 1995 a group of international NGOs and representatives of Indian farmers filed a legal opposition against the patent.
India succeeded because proved these were part of traditional Indian knowledge.
10
12
Basmati Case
Basmati Case
Basmati Case was an eyeopener for India, in the sense that it brought into spotlight an instance of gross exploitation of developing county rights. Geographical Indications
are relatively new instruments which are gaining rapid popularity in the trade and economic scenario, which recognize the heritage of a country in certain specialized goods and seek to protect the same. GI indicates the special protection that particular goods enjoy by the virtue of their geographical origin which renders them special and peculiar quality.
Basmati Case
THE FACTS Basmati:
Originally from India and Pakistan
Basmati became a controversial issue after RiceTec, a Texas-based company, in 1997, patented some types of rice they developed as American basmati.
RiceTec Inc,
trying to enter the international Basmati market with brands like Kasmati and Texmati.
Ultimately, the company claimed to have developed a new strain of aromatic rice by interbreeding basmati with another variety, as Texmati or American Basmati.
Issued the Patent number 5663484 on Basmati rice lines and grains on September 2, 1997.
Basmati Case
Objection:
by two Indian nongovernmental organizations (NGOs) Centre for Food Safety, an international NGO that campaigns against biopiracy, and the Research Foundation for Science, Technology and Ecology, an Indian environmental NGO who filed legal petitions in the United States. The Centre for Scientific and Industrial Research also objected to it. They sought trade protection for basmati rice of the Indian subcontinent and jasmine rice of Thailand. They demanded amendment of U.S. rice standards to specify that the termbasmati can be used only for rice grown in India and Pakistan, and jasmine for the Thai rice. The Indian government, after putting together the evidence, officially challenged the patent in June 2000.
Basmati Case
THE ISSUES
the answers to which are hoped to be answered through the emerging law of patents and geographical indications. Some of the major issues are:
Whether the term basmati is a generic one to describe aromatic rice, or does it refer specifically to the long aromatic rice grown in India and Pakistan? Whether the strain developed by RiceTec is a novelty?
Whether the basmati patent should be revoked in the light of protests from India?
Basmati Case
Importance of Basmati in India and Pakistan Economy
Rice is an important aspect of life in the Southeast and other parts of Asia.
More substantively, Indian farmers export $250 million in Basmati every year and U.S. is a target market
the main aim for obtaining the patent by RiceTec Inc. is to fool the consumers in believing there is no difference between spurious Basmati and real Basmati.
Basmati Case
theft involved in the Basmati patent is,
a theft of collective intellectual and biodiversity heritage on Indian farmers, a theft from Indian traders and exporters whose markets are being stolen by RiceTec Inc., and finally a deception of consumers since RiceTec is using a stolen name asmati for rice which are derived from Indian rice but not grown in India, and hence are not the same quality.
RiceTec Inc.
had attempted to sell its long-grain rice in Europe under such brand names as Texmati and Kasmati but not as Basmati. However, if the patent is not revoked, RiceTec Inc., can now sell its rice under the brand name Basmati which will definitely cut into Indias and Pakistans global market share, especially as the rice grown in the US could be sold cheaper than the Indian and Pakistani varieties.
Basmati Case
CASE ANALYSIS
RiceTec has got a patent for three things:
growing rice plants with certain characteristics identical to Basmati, the grain produced by such plants, and the method of selecting rice based on a starch index (SI) test devised by RiceTec,
The patent was challenged on the fact that the plant varieties and grains already exist as a staple in India.
5 75 percent of U.S. rice imports are from Thailand and that the remainder is from India and Pakistan and both varieties are rice that cannot be grown in the United States.
The legal theory is that the patent is not novel and for an invention that is obvious, being based on rice that is already being imported in the United States, therefore it should not have been granted in the first place.
Basmati Case
Indias attorneys
to challenge the use of the term basmati in conjunction with the patent and in marketing of the rice. Such use of the term creates confusion as to geographic origin and usurps the goodwill and recognition established with basmati rice grown and sold from India.
Re-examination:
As a result of the re-examination application filed by the Indian government, RiceTec agreed to withdraw several of the claims.
In January 29, 2002, the United States Patent and Trademark Office issued a Reexamination Certificate canceling claims 1-7, 10, and 14-20 (the broad claims covering the rice plant) out of 24 claims and entered amendments to claims 12-13 on the definition of chalkiness of the rice grains
Basmati Case
Trademark law:
could also be a basis for challenging the use of basmati.
RiceTec and to prevent it from marketing basmati rice in a way that creates confusion with the Indian product.
But, in order to be successful on such a claim, the Indian government would have to show likelihood of confusion among consumers. RiceTec did not trademark the term basmati and it has been careful in marketing its product so as not to use the term basmati as an indication of source.
The Indian government could argue that this use of the term basmati is what creates confusion among consumers. The term basmati need not be federally registered as a trademark for India to raise the claim.
Basmati Case
Basmati, the word means fragrant and hence describes a major attribute of the product. . Descriptive marks are protected only if they have secondary meaning, that is, the term makes the ordinary consumer recognize the source of the product as opposed to the product itself. In this vein, RiceTec could also argue
that the term basmati has become a generic term for a particular category of rice and hence cannot be protected.
However, now it is much a settled position that geographical indicators need not necessarily indicate the place of origin, it could signify the product itself as long as it is known to possess certain qualities by the virtue of its belonging to certain place.
Basmati Case
If India loses the fight against RiceTec, the issue remains of what India can strategically do to protect its rights in basmati rice.
U.S. trademark law does not offer a successful avenue for India.
The TRIPS agreement expressly protects indicators of geographic origin and permits legal recourse through the WTO process to discontinue use of misleading geographic indicators. The problem with relying on TRIPS is the basmati is not a geographic indicator; the word literally, describes the scent of the rice, not its geographic source.
Basmati Case
One tactic that the government has recently pursued is to enact its own law granting protection to marks that indicate geographic origin. Basmati is arguably protected under these recently enacted provisions.
One argument that the Indian government made in challenging RiceTecs patent is that basmati should be treated like champagne and burgundy.
The TRIPS agreement expressly forbids trademark protection for geographic indicators as applied to wine and spirits. The United States has amended its trademark law to reflect this prohibition
Basmati Case
Basmati originated in Punjab which spans areas of both India and Pakistan. This explains why its only grown in those two countries. Punjab is one of the smallest states in India. However, its geology that is, its deep and fertile soils as well as its exceptional climate has a far reaching impact on India's economy.
Novartis (Glevec)
27
In Nov 2003, Novartis again applied for EMR for a period of five years.
Dr.B.S. Kuchekar 2008 28
29
The Cancer Patients Aid Association filed an opposition on behalf of cancer patients in the Chennai patent office.
30
31
32
33
34
35
36
Roche got patent for Flurazepam, API of Dalmane which expires on Jan. 1984. In early 1983, Bolar decided with interest to market a generic drug product equivalent to Dalmane after expiry of that patent.
37
Approval of an equivalent of an established drug can take more than 2 years. Bolar, not waiting for the patent to expire, started to obtain federal approval to market its generic version of Dalmen.
In mid-1983, Bolar obtained the patented drug from a foreign manufacturer to make capsules and carry out the stability, dissolution rate,bio-equivalence and blood serum studies necessary for a New Drug Application to the FDA.
38
Making, using, or selling any patented invention without authority constitute Infringement of patent.
Bolars intended experimental use is solely for for business purpose and not for amusement or to satisfy curiosity or for philosophical inquiry. Bolar infringes Roches Patent.
39
However as per IPA Amendment May 2003, Use of a patented product to experiment the scientific study, does not constitute an infringement.
40
41
42
Complaints from Pfizer against Ranbaxy alleging that Ranbaxys proposed ANDA product infringes the 893 and 995 patents.
43
US 5,273,995
Independent claim 1 covers atorvastatin acid and its salts Dependent claim 2 covers atorvastatin lactone
44
In response to Pfizers complaints, Ranbaxy alleges It does not infringe either the 893 or 995 patents. It also challenges the validity of the patent term extension granted by PTO for the 893 patent. It contends that the asserted claim 6, is invalid for double patenting, obviousness and anticipation. It also contends that the995 patent is unenforceable.
45
Court Decision: 1. Pfizer had ample data to support the claims it made to the PTO for US 4,681,893 which was scientifically sound. 2. Instances of non-discloser cited by Ranbaxy are sufficient to demonstrate an intent to deceive the PTO. 3. Also Ranbaxy has not met its burden of establishing inequitable conduct.
46
Court concludes: Pfizer has established that Ranbaxys ANDA product literally infringes the 893 and 995 patents, Judgment: In favor of Pfizer and against Ranbaxy. (Dec.23,2005) Ranbaxy appealed in court of appellate i.e. Federal court. Ranbaxy partially own the case.
47
Practically hemicalcium salt (claim 6) of atorvastatin lactone (claim 2) is not possible, instead hemicalcium salt is Dr.B.S. is invalid due to improper claim dependency and drafting possible for atorvastatin acid (claim 1), so court held patentKuchekar 2008
48
Mar 2008: Presently Pfizer has settled All Lipitor Patent Litigations with Ranbaxy worldwide
49
During hearings, Cipla counterclaimed that the patent was invalid and should be revoked. The trial judge,
refused to grant an interim injunction on the ground that since Cipla was selling the drug at 1/3rd of the price of Roche, an injunction would have meant lack of affordable access for a large number of cancer patients in India. Therefore, "public interest" demanded that no injunction (restraining order) be granted
The interesting part was that the claims were not even construed during the trial even once.
In March 1999 the Indian government amended its patent law to allow companies to file mailbox pharmaceutical patent applications prior to the launch of Indias product patent regime.
The law applied retrospectively from January 1 1995 and the Patent Office began to examine them in 2005, after the law was changed to allow product patents to be issued for pharmaceuticals. The trial judge refused to grant an interim injunction on the ground that since Cipla was selling the drug at 1/3rd of the price of Roche, an injunction would mean impeding affordable access for a large number of cancer patients in India. Therefore, public interest demanded that no injunction (restraining order) be granted.
The Court also imposed a cost of Rs five lakh (US $ 10,000) on Roche.
It has to remembered that Section 3(d) of Indias Patent Act, which was challenged by Novartis in the courts last year, was also the feature in the case. Section 3(d) restricts what can be patented.
In particular, the section states that salts and other derivatives of known substances shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.
The second line of argument was that since neither Tarceva (Roche's product), nor Erleva (Natco's product) could be associated with the patent in question, there could be no infringement.
Natco responded, not surprisingly, that the pre-grant was neither final nor binding, and that Indian patent law allowed anyone to question the validity of a patent at any stage. It also argued that the fact that Natco's not filing a postgrant opposition was inconsequential.
With that, the matter has now been adjourned and been made a part heard matter and will be heard by Justice Shali on the 16th of July 2010
In particular, the section states that salts and other derivatives of known substances shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.
In December 2008, the Madras High Court in Chennai decided to set aside Roches patent until these arguments could be heard.
Supreme Court
Following the rejection of the pre-grant opposition by the patent office, the public interest groups approached Indias Supreme Court. The Supreme Court directed the groups to join the post-grant opposition proceedings that were already taking place through oppositions filed by generic companies and the Delhi Network of Positive People (DNP+).
Cipla
Launched India in September 2008, even while the drug enjoyed patent protection in following the grant of patent in 2007.
Roche Vs Wockhardt
Roche and Wockhardt
Roche got its first product patent in India in 2006 for Hepatitis Drug Pegasys. (Pegylated interferon alfa-2a). Its first and forthcoming patents all were being attacked by Indian Generics (not to forget various NGOs) whether through series of oppositions filed or counter attacking to Roches suits of infringement.
Roche Vs Wockhardt
It was argued that the claimed invention,
the branched pegylated form of interferon alfa 2a did not satisfy the patentability criteria under Indian law as Pegasys involves combining interferon with polyethelyene glycol (PEG) which helps the interferon to remain in the bloodstream, and also that the technology of combining interferon and other biologically active proteins with PEG had been known for years prior to Pegasys patent. In light of this, the counsel put forward that there was no inventive step and was obvious to a person skilled in the art. Further, they alleged that Roches invention is at most a mere admixture of known substances and thus not patentable under section 3(e) of the Patents Act 1970, and is just a new form of a known substance and not patentable under section 3(d) of the Act.
Roche Vs Wockhardt
Roche and Wockhardt
Interestingly, Assistant Controller T.V. Madhusudan (in March 2009) ruled against the recommendation of Opposition Board to revoke the patent and held the patent to be valid. Roche successfully cleared the enhanced efficacy test in the Section 3d of the Indian Patent Act (including the novelty and obviousness tests).
Roche Vs Wockhardt
Section 3d
allows a novel derivative of a known compound only when such derivative shows enhancement in known efficacy of a known compound. The efficacy is defined as therapeutic efficacy as per Madras High Court decision in Novartis Gleevec Case. Interferon
known compound and known efficacy is its antiviral and anti proliferative activity and the experimental results in the patent showed that there is indeed enhancement of therapeutic efficacy which resulted in Roches victory.
used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B. Like zanamivir, oseltamivir is a neuraminidase inhibitor. It acts as a transition-state analogue inhibitor of influenza neuraminidase, preventing progeny virions from emerging from infected cells. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed.
It is a prodrug, which is hydrolysed hepatically to the active metabolite, the free carboxylate of oseltamivir (GS4071).
opposed granting of patents rights to Gileads Tamiflu did not have inventive step a pre-requisite for products to gain patents in India.
Tamiflu is only a derivative and pharmaceutically acceptable salts, solvates and derivatives, dissolved enantiomers and purified diastereomers in the claimed composition are clearly not patentable under section 3(d) of the Indian Patent Act.
the decision
it found anti-influenza agent oseltamivir to fall within the provisions of section 3(d) and not patentable.
The Delhi Patent Office particularly relied on the decision of European Board of Appeal (T-0133/01) stating that alleged but unsupported advantages cannot be taken into consideration in respect of the determination of the problem underline the claimed invention.
Any person may, in writing, represent the opposition to the controller against the grant of patent within a minimum period of 6 months, from the date of publication is provided for making representation as against the present period of 3 months, for filing pre-grant opposition.
The grounds of pre-grant opposition in the Ordinance were novelty, inventive step and industrial applicability, non-disclosure or wrongful mentioning of source and geographical origin of biological material and anticipation of invention by knowledge, oral or otherwise, available in public domain.
However, Cipla received marketing approval from the drug controllergeneral of India in January 2006.
The drug will be priced at about Rs 1,000 per strip of 10* 75 mg tablets less than half the current Tamiflu market price of $60.
SB and Fujimoto
88
SB had filed a process patent in Japan on Cimetidine in September 1973. Granted in 1981 and was valid up to Sept 1993.
In December 1986,Fujimoto imported the infringing product from Yugoslavia and sold 68,000 tablets in Japan, Fujimoto also manufactured a generic version of Cimetidine
89
SB claimed that Fuimoto had infringed their patent from Dec. 1986-Sept. 1993 Fujimoto argued that their process was not covered by the SmithKline patent
The Judge found Fujimoto liable for patent infringement. (Tokyo District Court,1998.)
90
SmithKline Beecham(SB) V/s Fujimoto Pharmaceutical Co.. The Court awarded SB and SBS Yen 500 million($4.2 million) in royalties and Yen 2.5 billion($21 million) in lost profit based on a 15% profit rate.
91
92
The Patents
Upjohn United States Patent No. 4,916,163
(the '163 patent) anti-diabetic pharmaceutical composition containing at least 70% by weight of spray-dried lactose as the preponderant excipient. Active ingredient- micronized glyburide. Improvements- the excipients comprise a glidant, lubricant and disintegrant.
MOVA
Active Ingredients : Micronized glyburide Inactive ingredietsn: spray-dried lactose as an excipient. But contains
49% by weight of spray-dried lactose and 46.3-49.1% of Starch 1500 (pregelatinized corn starch).
93
Issues: Infringement.
Whether MOVA infringes under the doctrine of equivalents. The court found that
there were differences between the excipient behavior of Starch 1500 and spray-dried lactose, particularly that Starch 1500 operates by disintegration instead of dissolution.
Starch 1500 disintegrates, breaks up the tablet and releases the active ingredient and the active ingredient is dissolved Spray-dried lactose tablet- the drug is released as the lactose dissolves
94
Issues: Validity
The obviousness arguments and the prior art examined The Rothe Patents.
These patents showed micronized glyburide and, as the pharmaceutical excipient, ordinary lactose. Company was able to show that using lactose which is not spraydried does not yield a formulation which is easily and readily manufacturable,"
[micronized anti-diabetic drug] 100 mg Gum tragacanth 10 mg Lactose (sprayed-dried) 197.5 mg Corn starch 25 mg, Talc 15 mg Magnesium stearate 2.5 mg
96
97
segregation and aggregation problems arise during direct compression of formulations containing micronized drugs .
using this high percentage of spray-dried lactose with a micronized active ingredient. teaches away from direct compression by suggesting use of wet granulation to avoid these problems.
98
99
MOVA does not suggest that either the pharmacologic effect or the physical properties of tetracycline is similar to glyburide.
100
Conclusion
The federal court affirmed the judgment of non-infringement and reversed the judgments of invalidity and unenforceability.
101
Learning
The importance of the application of the doctrine of equivalents in an infringement analysis relating of a formulation patent When a formulation patent consists of a combination of two or more elements, it is important to substitute at least one element that performs the same function in a different way The case is a good example of the way in which the court applies an obviousness analysis to a series of prior art references Gives you some idea of what a prior art reference should teach or contain in order to render a patent claim obvious
102
IPR Case
Status: 18Apr2010
Section 107A of the Patents Act clearly exempts from patent infringement any of acts of making, using or even selling a patented invention, in so far as such acts are necessary to obtain information for the filing of a drug regulatory application before the authority.
Bayer
In August, 2009, a single-judge bench of the Delhi High Court had rejected Bayers attempt to bring patent linkage
a system that can delay the entry of low-cost generic drugs into the market by making the drugs controller general of India (DCGI) act like patent police and refuse marketing approval to generics if the innovators hold a patent in India.
Adams Vs Perrigo
Doctrine of Equivalence
Adams Vs Perrigo
U.S. Patent 6,372,252
Adams Therapeutics , Mucinex, Extended release formulation of guaifenesin, In 2007, Perrigo filed an Abbreviated New Drug Application for its own extended release guaifenesin product,
alleging in its paragraph (iv) certification (see 21 USC 355(j)(2)(A)(vii)(IV)) that the claims of the 252 patent are invalid or would not be infringed by the Perrigo product.
Adams Vs Perrigo
Because the highest AUC value for Perrigos product was 3493.38 hr*g/mL, Adams sought to use the doctrine of equivalents to establish infringement.
However, the district court determined that the phrase at least 3500 designated an absolute lower limit, such that resort to the doctrine of equivalents would impermissibly vitiate a claim limitation.
Adams Vs Perrigo
The Federal Circuit disagreed with the district court, noting the following:
Previous Federal Circuit decisions permitted application of the doctrine of equivalents to numeric ranges.
The at least language does not change the analysisat least is just the simplest way to express greater than or equal to. The lack of words of approximation (such as about) may affect the literal infringement analysis, but does not foreclose the doctrine of equivalents.
Adams Vs Perrigo
Providing guidance to the district court on remand, the Federal Circuit explained:
The proper inquiry is whether the accused value is insubstantially different from the claimed value.
Also interesting is the Federal Circuits footnote that caution[s] against reading the term 3500 with greater precision than it deserves. The court makes reference to the concept of significant digits, noting that, [i]n some scientific contexts, 1 represents a less precise quantity than 1.0
Adams Vs Perrigo
It seems to me that interpreting and applying the claim language under a significant digits approach could bring the accused product within the literal scope of the claim.
If the claimed value (3500) is interpreted as having only two 2 significant digits, and the accused value is reported with 2 significant digits for comparison, the 3493.38 accused value would be reported as 3500. Since 3500=3500, the accused product would literally meet this claim limitation.
Adams Vs Perrigo
The modified release product of claim 26 [which claims the modified release product of claim 24 wherein the total quantity of guaifenesin is 600 mg]
wherein the Cmax of said product is at least 1000 ng/mL and said product has an AUCinf of at least 3500 hr*ng/mL.
Adams Vs Perrigo
The district court stated that
the term at least indicates an absolute lower limit of the range, citing Quantum Corp. v. Rodime, It stated that allowing Adams to show infringement under the doctrine of equivalents would vitiate the 3500 hr*ng/mL claim limitation. On appeal, Adams argues that it should be allowed to establish infringement under the doctrine of equivalents. Adams asserts that we previously concluded that infringement under the doctrine of equivalents could apply to claims requiring a specific numeric range.
Adams Vs Perrigo
It asserts that the question is whether Perrigos AUC value is insubstantially different from the claimed AUC value
Adams contends that because 3494.38 hr*ng/mL is only 0.189% different from 3500 hr*ng/mL, a genuine issue of material fact exists with respect to whether the two values are insubstantially different.
Perrigo argues that because claim 34
does not use words of approximation, Adams cannot expand this element to ensnare Perrigos ANDA product. Perrigo asserts that [t]his Court has expressly held that the claim term at least means as the minimum and there-fore when coupled with a specific number sets forth an absolute lower limit of a range
Adams Vs Perrigo
The addition of at least in this case does not change this analysis. At least 3500 is the simplest way to express greater than or equal to 3500, an open-ended range. We vacate the order of the district court
United States Court of Appeals for the Federal Circuit 02-1348 GLAXO WELLCOME INC., Plaintiff-Appellant, v. ANDRX PHARMACEUTICALS, INC., Defendant-Appellee.
Glaxo Vs Andrx
Glaxo Wellcome, Inc. appeals the decision of the United States District Court for the Southern District of Florida, holding on summary judgment that United States Patent No. 5,427,798 (the '798 patent) is valid but not infringed by the bupropion products of Andrx Pharmaceuticals, Inc.[1]
We conclude that the district court erred in its construction of the '798 claims.
On the correct claim construction, we vacate the summary judgment of noninfringement and remand for further proceedings.
Glaxo Vs Andrx
BACKGROUND Glaxo Products :
antidepressant medicine having the brand name WellbutrinSR and the smokingcessation medicine having the brand name Zyban.
The active ingredient of both products is bupropion hydrochloride. Glaxo manufactures and sells sustained release formulations of these products;
sustained release extends the medicinal action of the bupropion so that less frequent doses are required, and avoids the surge of bupropion that had occasionally caused seizures upon ingestion.
Sustained release formulations must maintain an effective level of the medicine in the bloodstream for an optimum period without unacceptable deviation in pharmacologic activity.
Glaxo Vs Andrx
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 Wellbutrin7SR and Zyban7. Andrx also filed a Paragraph IV certification, asserting that the Andrx products do not infringe the Glaxo '798 patent or that the patent is invalid:
Glaxo duly filed suit against Andrx for infringement of the '798 patent, in accordance with these statutory provisions
Glaxo Vs Andrx
The following claims of the '798 patent are representative: 1. A controlled sustained release tablet comprising 25 to 500 mg of bupropion hydrochloride and hydroxypropyl methylcellulose,
the amount of hydroxypropyl methylcellulose to one part of bupropion hydrochloride being 0.19 to 1.1 and said tablet having a surface to volume ratio of 3:1 to 25:1 cm-1 and said tablet having a shelf life of at least one year at 59" to 77"F. and 35 to 60% relative humidity, said tablet releasing between about 20 and 60 percent of bupropion hydrochloride in water in 1 hour, between about 50 and 90 percent in 4 hours and not less than about 75 percent in 8 hours.
Glaxo Vs Andrx
The following claims of the '798 patent are representative:
14. A controlled sustained release tablet comprising an admixture of 100 mg of bupropion hydrochloride and hydroxypropyl methylcellulose which after oral administration of a single one of said tablets in adult men produces plasma levels of bupropion as free base ranging between the minimum and maximum levels as shown in Fig. 5 over twenty-four hours.
18. A sustained release tablet containing a mixture of (a) 100 mg of bupropion hydrochloride and (b) means for releasing between about 25 and 45% of bupropion hydrochloride in one hour, between 60 and 85% in 4 hours and not less than 80% in eight hours in distilled water said means comprising hydroxypropyl methylcellulose.
Glaxo Vs Andrx
In determining the meaning and scope of patent claims, the court gives primary consideration
to the specification and
the prosecution history, and may consider the prior art and technical treatises and dictionaries.
If relevant and helpful, the court may receive the testimony of experts in the field of the invention
Glaxo Vs Andrx
The issues of claim construction and infringement focused on the controlled release agent, hydroxypropyl methylcellulose (HPMC). HPMC is defined in the Handbook of Pharmaceutical Additives as follows:
Definition: Propylene glycol ether of methyl cellulose Properties: White powd.; swells in water to produce a clear to opalescent visc. colloidal sol'n.; nonionic, insol. in anhyd. alcohol, ether, chloroform; sol. in most polar solvs. Trade Names: Benecel7 Hydroxypropyl Methylcellulose; Methocel7 E3 Premium; Methocel7 E4M Premium; Methocel7 E5P; Methocel7 E6 Premium; Methocel7 E10MP CR; Methocel7 E15LV Premium; Methocel7 E50LV Premium; Methocel7 E50P; Methocel7 E Premium; Methocel7 F4M Premium . . . .
Glaxo Vs Andrx
The specification describes the hydroxypropyl methylcellulose release agent as follows:
This invention is directed to control sustained release (SR) tablets containing bupropion hydrochloride (as the drug or active ingredient), preferably hydroxypropyl methylcellulose (Methocel7) for controlling drug release rate, and cysteine hydrochloride or glycine hydrochloride. Methocel is the brand name for hydroxypropyl methylcellulose (HPMC) from Dow Chemical. Other companies also supply HPMC. In order to prepare the controlled sustained release (SR) tablets of this invention, particles of bupropion hydrochloride are preferably blended with microcrystalline cellulose and hydroxypropyl methylcellulose (Methocel7) to form an admixture of blended powders. In the practice of this invention, for every part by weight of bupropion hydrochloride, the amount of hydroxypropyl methylcellulose is 0.19 to 1.1 and more preferably 0.267 to 0.68 parts by weight . . . .
Glaxo Vs Andrx
'798 patent, col.1:67 - col.3:14. The specification describes the HPMC used in the examples as follows:
Hydroxypropyl Methylcellulose 2910, USP used in the examples, conforms to 28.0 to 30.00% methoxyl substitution and 7.0 to 12.0% hydroxypropyl substitution. The preferred nominal viscosity of 2% solution in water is not less than 3,000 centipoise and not more than 5,600 centipoise. It is supplied by Dow Chemical Company, Midland, Mich. as Methocel E4M Premium CR.
Glaxo Vs Andrx
The examiner stated:
The rate of release is directly related to the release retarding effect of hydroxypropylmethylcellulose. While other excipients have been disclosed, the particular cellulose is considered critical for controlled and/or sustained release and should be incorporated into the independent claims.
The disclosure of a single species does not provide a basis for claiming a generic concept.
Glaxo Vs Andrx
The applicant acquiesced, and limited all the claims to hydroxypropyl methylcellulose. However, the examiner did not require limiting the hydroxypropyl methylcellulose to any specific grade or molecular weight. What the examiner required was:
Applicants are claiming a tablet which provides a distinct release profile. The advantages provided by the unique tablet differ from an instant release tablet. The limitations of claims 2-3 are considered critical and should be incorporated into claim 1 for proper enablement.
Glaxo Vs Andrx
In response, the applicant amended claim 1 to include the limitations: "said tablet releasing between about 20 and 60 percent of bupropion hydrochloride in water in 1 hour, between about 50 and 90 percent in 4 hours and not less than about 75 percent in 8 hours.
Glaxo Vs Andrx
The examiner did not require "a particular grade" of HPMC. The district court erred in holding that the amendment adding the release rate data to the claim limited the claim to the grade of HPMC in the example. The district court stated: "All grades of HPMC could no longer be read into the Glaxo claims to a certainty after the amendment which recognized that a particular grade was critical for controlled or sustained release, therefore an invitation was extended to refer elsewhere for particular grade information." Neither the applicant nor the examiner stated that "a particular grade was critical"; the amendment stated the parameters of the claimed release, not a particular grade of hydroxypropyl methylcellulose.
The HPMC was not limited to the specific example of grade 2910
Glaxo Vs Andrx
Andrx states
that its HPMC has a significantly lower molecular weight and viscosity than those of grade 2910, and that the Andrx HPMC does not affect the rate of release because it is readily soluble. Andrx states that it controls the release of bupropion in other ways, not by way of the HPMC in its tablets. Andrx states: "In the Andrx ANDA products, the Eudragit7E100/Ethocel 100 layer is the release controlling means. This polymer mixture forms a polymeric membrane that regulates the amount of drug that is allowed to release from the pellets by diffusion through the membrane." Andrx also states that its tablets do not exhibit the dissolution and blood plasma profiles required by the claims.
Glaxo Vs Andrx
Glaxo challenges these statements, pointing out that
Andrx was unable to produce a satisfactory controlled release product without using HPMC, and that Andrx has represented to the FDA that its tablets are bioequivalent to the Glaxo tablets, as is required for an ANDA, and thus necessarily match the release rate, dissolution, and blood plasma profiles of the federally approved formulation.
Glaxo Vs Andrx
Glaxo states that hydroxypropyl methylcellulose is a polymer and exists in a range of molecular weights, that it is incorrect to construe the claims as limited to a particular grade of hydroxypropyl methylcellulose, and that the specification contains no basis for either a molecular weight or a viscosity limitation.
Glaxo argues that while the specification shows the HPMC 2910 (supplied as Methocel E4M Premium CR) that Glaxo used, the description of the invention does not limit the HPMC to a particular grade
Glaxo Vs Andrx
Glaxo states that hydroxypropyl methylcellulose is a gel-forming material known for use in pharmaceutical formulations. There was extensive evidence to this effect. Professor Kathryn E. Uhrich (Rutgers University) testified as follows: I: Significantly, all grades of HPMC are capable of forming a hydrogel that contributes to sustained release when exposed to aqueous media, including the HPMC E5 grade of the Andrx ANDA products. Andrx's products use HPMC E5 and clearly fall within the patented claim element for HPMC. The accused products contain admixtures of HPMC E5 with bupropion and the resulting tablets are sustained release tablets where the HPMC E5 contributes to the release.
Glaxo Vs Andrx
II The hydroxypropyl methylcellulose [in the Andrx products] is essential for the sustained or extended release of bupropion hydrochloride as a result of, among other things, the interactions of the hydroxypropyl methylcellulose with the adjacent bupropion/hydroxypropyl methylcellulose, as well as with the other polymers in the formulation during both manufacture and drug release.
The hydrophilic properties of hydroxypropyl methylcellulose and its ability to swell in the presence of solvents such as water and certain organic solvents are also important in controlling release.
Therefore, in Andrx's proposed 100 mg and 150 mg products, a means for releasing bupropion hydrochloride is hydroxypropyl methylcellulose as required by Claims 18 and 19.
Glaxo Vs Andrx
Dr. Banakar, Andrx's expert, described by Andrx as world renowned, testified that a person of ordinary skill in the art of drug formulation reading the '798 patent would understand that hydroxypropyl methylcellulose only includes certain grades of HPMC which are high-viscosity and hydrogel-forming. Dr. Banakar stated:
If the term "hydroxypropyl methyl cellulose" as used in Claims 1, 14, 15, 18 and 19 of the '798 patent includes low-viscosity, low molecular weight grades of HPMC, then the '798 patent is not enabling of the claimed invention because it does not teach or enable one skilled in the art to make a sustained-release bupropion formulation having the dissolution profiles of Claims 1, 18 or 19 or the blood plasma drug levels of Claims 14 or 15. That is, for a product to exhibit the dissolution profile recited in Claim 1 of the '798 patent, and only require the use of bupropion and HPMC, at the specified ratio, the HPMC must be of a high molecular weight, high-viscosity release-controlling grade. Use of a low-viscosity, low molecular weight soluble grade of HPMC such as the E5 grade at the recited ratios without some other sort of release-controlling technology added would make it impossible for one of ordinary skill in the art to obtain the required dissolution profile.
Glaxo Vs Andrx
In fact, in order to obtain a suitable sustained release formulation, which uses HPMC E5 as a binding agent and/or seal coat, constituent, Andrx needed to employ a completely different and novel release technology. . . . The Andrx ANDA products do not employ hydrogel technology to control the release of bupropion. Instead, the Andrx ANDA products employ pellets (compressed into a tablet) having certain polymer coatings thereon, which control bupropion release by diffusion.
Glaxo Vs Andrx
Dr. Nicholas Peppas (Professor of Pharmacology, Purdue University) described by Glaxo as one of the world's leading scientific experts in hydrogels, disagreed with Dr. Banakar:
Each of Andrx's products comprises hydroxypropyl methylcellulose and bupropion hydrochloride and the hydroxypropyl methylcellulose is an essential component for the extended and sustained release of bupropion hydrochloride. Its presence in Andrx's formulations and the interactions of the hydroxypropyl methylcellulose with other components inside of this formulation lead to the formation of a gel region in the polymer matrix, which, as I have shown in paragraphs 31, 32 and 36, is a controlling step of the overall release process.
Glaxo Vs Andrx
Dr. Nicholas Peppas (Professor of Pharmacology, Purdue University) described by Glaxo as one of the world's leading scientific experts in hydrogels, disagreed with Dr. Banakar:
I disagree with Dr. Banakar's opinion [Andrx's expert] with respect to the characteristics of hydroxypropyl methylcellulose and with Dr. Banakar's opinion that a person working in drug formulation or pharmaceutics would interpret Claims 1, 13, 14, 15, 17 and 19 of the '798 patent as limited only to hydroxypropyl methylcellulose grades that form "hydrogels" and would not include "low viscosity grades" of hydroxypropyl methylcellulose. In my opinion, and based on my experience, Dr. Banakar is incorrect in defining "low viscosity" grades of hydroxypropyl methylcellulose as not being "hydrogels." For lower viscosity hydroxypropyl methylcellulose grades, these gels may be somewhat less dense than for higher viscosity hydroxypropyl methylcellulose grades, but the gels formed during swelling definitely control the drug release process in Andrx's products.
Glaxo Vs Andrx
Although the expert testimony is facially in conflict, it was not disputed that the mechanism whereby HPMC affects the release of materials with which it is mixed is the swelling of the HPMC in contact with water. It was not disputed that Andrx mixes the bupropion with HPMC in the interior portion of its tablets. Andrx did not establish that the HPMC it used to mix with the bupropion did not swell in water and affect the rate of release of the bupropion, while arguing that other chemicals affect diffusion. Glaxo stresses that in the Andrx formulation the HPMC is mixed with the bupropion at the core of the tablet, as in the '798 patent.
Glaxo Vs Andrx
Andrx in turn stresses that both Andrx and Glaxo use a rapidly soluble grade of HPMC as outer coatings of the tablet. The '798 patent describes the Glaxo outer coating as a thin film of HPMC that does not "substantially affect the release rate of the bupropion hydrochloride from the tablet, since the coating is instant release which rapidly dissolves in the stomach." The '798 specification explains that "because of the nature of the film coating, the release rate will be substantially the same whether or not the tablets are film-coated." Andrx states that it uses this same grade inside its tablet in admixture with the bupropion, and therefore that it cannot contribute to controlling the rate of bupropion release.
Glaxo Vs Andrx
Glaxo responds with the testimony of Andrx's formulation scientist, Mr. Jianbo Xie, that he and others at Andrx had been unable to produce a sustained release bupropion product without using HPMC, although they had tried to do so because of the Glaxo patent.
Glaxo Vs Andrx
As a matter of claim construction, the intrinsic and extrinsic evidence lead to the conclusion that the HPMC mixed with the bupropion at the core of the tablet is not limited to a particular grade and molecular weight, provided only that the claimed limitations of release rate and plasma levels are met. When a claim term has an accepted scientific meaning, that meaning is generally not subject to restriction to the specific examples in the specification.
It is established that "as a general rule claims of a patent are not limited to the preferred embodiment . . . or to the examples listed within the patent specification.") ("preferred embodiments, without more, do not limit claim terms").
Glaxo Vs Andrx
In this case the properties and use of hydroxypropyl methylcellulose to control release were well known.
The examination record showed that patentability turned on the ratio of the HPMC to the bupropion, the shelf life, the rate of release, the duration of release, and the plasma levels.
The hydroxypropyl methylcellulose used in admixture with the bupropion hydrochloride is not limited to the grade and molecular weight of HPMC in the specific examples, but the claims, correctly construed, require that HPMC be present in the stated amount, and that the product have the release rate and duration and plasma levels and other properties set forth in the claims
Glaxo Vs Andrx
The factual issues arising under the doctrine of equivalents were similarly unresolved. In view of our ruling that literal infringement is not limited to a particular grade of HPMC, but that Glaxo must establish that all of the claim limitations are met by the Andrx product, the premise of district court's ruling on equivalency is no longer applicable.
Further, that holding was based on the Federal Circuit's decision in Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 234 F.3d 558 (Fed. Cir. 2000) (en banc), which was vacated after the district court's decision. Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722 (2002). Thus the district court's decision on this ground is vacated.
Glaxo Vs Andrx
CONCLUSION We conclude that the claims are not limited to a specific grade of hydroxypropyl methylcellulose as used in admixture with the bupropion. The summary judgment of noninfringement is vacated, and the case is remanded for further proceedings.