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Medicines Co. v. Mylan Inc.

United States District Court, N.D. Illinois, Eastern Division

October 27, 2014

THE MEDICINES COMPANY, Plaintiff,
v.
MYLAN INC., MYLAN PHARMACEUTICALS INC., and BIONICHE PHARMA USA, LLC, Defendants

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[Copyrighted Material Omitted]

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[Copyrighted Material Omitted]

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[Copyrighted Material Omitted]

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For The Medicines Company, Plaintiff, Counter Defendant: David A. Zwally, Frommer Lawerence & Haug LLP, New York, NY; John Bostjancich, Patricia Susan Smart, Smart & Bostjancich, Chicago, IL; Porter F. Fleming, Frommer Lawrence & Haug LLP, New York, NY; Angus Chen, Frommer Lawerence & Haug LLP, New York, NY; Jason A. Lief, Morgan Lewis & Bockius LLP, New York, NY.

For Mylan Inc., Mylan Pharmaceuticals Inc., Bioniche Pharma USA, LLC, Defendants, Counter Claimants: David E. Jones, LEAD ATTORNEY, PRO HAC VICE, Perkins Coie LLP, Madison, WI; Autumn N. Nero, David J. Harth, Emily J. Greb, PRO HAC VICE, Perkins Coie LLP, Madison, WI; James B Coughlan, Perkins Coie LLP, Chicago, IL; Scott D. Eads, PRO HAC VICE, Perkins Coie LLP, Portland, OR; Shannon M. Bloodworth, PRO HAC VICE, Perkins Coie LLP, Washington, DC.

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MEMORANDUM OPINION AND ORDER

AMY J. ST. EVE, United States District Judge.

In this patent infringement action, The Medicines Company (" TMC" ) asserts that Defendants' proposed generic bivalirudin drug product infringes United States Patent No. 7,582,727 (the " '727 patent" ). Specifically, TMC claims that Defendants Mylan, Inc., Mylan Pharmaceuticals Inc. and Bioniche Pharma USA, LLC (collectively, " Mylan" ) proposed generic bivalirudin drug infringes claims 1-3, 7-10, and 17 of the '727 patent. ( See R.1, Compl.; PTX 397, Parties' Statement of Uncontested Facts, ¶ 38.) Mylan disputes that its proposed drug infringes the '727 patent and asserts that the '727 patent is invalid on grounds of anticipation, obviousness, and non-enablement and unenforceable for inequitable conduct. The Court held a bench trial on TMC's infringement claim and Mylan's counterclaims regarding the '727 patent.[1] Having considered the evidence and the parties' arguments, the Court finds as follows: (1) Mylan failed to prove by clear and convincing evidence that claims 1-3, 7-10, and 17 of the '727 patent are invalid or unenforceable; and (2) Mylan's proposed bivalirudin drug product infringes claims 1-3, 7-10, and 17 of the '727 patent.

BACKGROUND

I. The '727 Patent

The '727 patent was filed with the United States Patent and Trademark Office (" PTO" ) as U.S. Application No. 12/180,553

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on July 27, 2008 and issued as the '727 patent on September 1, 2009. (PTX 1, '727 patent; see PTX 397, ¶ 6.) The '727 patent is entitled " Pharmaceutical Formulations of Bivalirudin and Processes of Making the Same." ( Id.) Dr. Gary Musso and Dr. Gopal Krishna are the named inventors of the '727 patent, but TMC owns all rights, title, and interest to the '727 patent.[2] (PTX 397, ¶ ¶ 8, 9.)

The '727 patent generally pertains to pharmaceutical formulations of bivalirudin, a reversible thrombin inhibitor used to temporarily prevent blood clotting during catherization procedures. ( See id., at col. 1:21-56; PTX 397, ¶ 6.) The section of the '727 patent entitled " Background of the Invention" states: " [o]ne class of anticoagulants is direct thrombin inhibitors that disrupt the activity of thrombin, an important protein in the coagulation cascade." ( Id., col. 1:49-51.) The '727 further states: " [i]n particular, bivalirudin (ANGIOMAX® ), which directly inhibits thrombin by specifically binding to both its catalytic site and to the anion-binding exosite, is regarded as a highly effective anticoagulant for use during catherization [sic] procedures." ( Id., col. 1:52-56.) The medical and therapeutic applications of bivalirudin, make it " essential that the bivalirudin formulation maintains a high level of purity." ( Id., col. 2:1-3.) The compounding process for the bivalirudin formulation may generate impurities, such as Asp9-bivalirudin (from deamidation of asparagine at position 9 of bivalirudin to aspartic acid) and D-Phe12 impurities (from isomerization of L-phenylalanine at position 12 of bivalirudin to the D-isomer). ( Id. at col. 2:1-13.) The '727 patent also relates to development of processes for synthesizing bivalirudin that minimize the generation of impurities and pharmaceutical batches produced by such processes. ( Id. at col. 2:19-22.) By way of background, this compounding process involves three basic steps. ( See DTX 1080, Compounding Instructions-Bivalirudin Formulation, at MEDMYL4509463, MEDMYL450971.) First, the active pharmaceutical ingredient (" API" ), bivalirudin, is dissolved into a mannitol solution to form a bivalirudin solution. Second, the resulting bivalirudin solution is mixed with a pH-adjusting solution, such as sodium hydroxide, to raise the pH of the bivalirudin API to an acceptable level. Third, the mannitol solution and the pH-adjusting solution are removed from the mixture to form the final drug product.[3]

The asserted claims describe pharmaceutical batches of bivalirudin. Specifically, claim 1 of the '727 patent teaches " pharmaceutical batches" of bivalirudin having a maximum Asp9 impurity level of 0.6%. (PTX 1, col. 25:56-64.) Dependent claims 2 and 3 contain even stricter limitations on Asp9 impurities, reducing the maximum allowable level of Asp9 impurities to 0.4% and 0.3%, respectively. ( See id. at col. 25:65-26:56.) Dependent claims 7-10 and 17 contain all the limitations of claim 1 and additional limitations regarding the maximum level of D-Phe12-bivalirudin impurities (claim 7), the type of pharmaceutically acceptable carrier contained

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in the final drug product (claims 8-10), and the base used to adjust the pH of the final drug product (claim 17). ( See id. at col. 27-28.)

The asserted claims of the '727 patent read as follows:

1. Pharmaceutical batches of a drug product comprising bivalirudin (SEQ ID No: 1) and a pharmaceutically acceptable carrier for use as an anticoagulant in a subject in need thereof, wherein the batches have a pH adjusted by a base, said pH is about 5-6 when reconstituted in an aqueous solution for injection, and wherein the batches have a maximum impurity level of Asp9-bivliarudin of about 0.6% as measured by HPLC [high-performance liquid chromatography].
2. The pharmaceutical batches of claim 1, wherein the maximum impurity level of Asp9-bivalirudin does not exceed about 0.4% as measured by HPLC.
3. The pharmaceutical batches of claim 2, wherein the maximum impurity level of Asp9-bivalirudin does not exceed about 0.3% as measured by HPLC.
7. The pharmaceutical batches of claim 1, wherein the batches have a maximum level of D-Phe12-bivalirudin that does not exceed about 2.5% as measured by HPLC.
8. The pharmaceutical batches of claim 1, wherein the pharmaceutically acceptable carrier comprises one or more of a bulking agent or a stabilizing agent.
9. The pharmaceutical batches of claim 8, wherein the bulking agent is a sugar.
10. The pharmaceutical batches of claim 9, wherein the sugar is mannitol.
17. The pharmaceutical batches of claim 1, wherein the base is sodium hydroxide.

(PTX 1, col. 25:55-28:9.) During claim construction, the Court construed the term " pharmaceutical batches" as follows:

" Pharmaceutical batches" may include a single batch, wherein the single batch is representative of all commercial batches (see generally, Manual of Policies and Procedures, Center for Drug Evaluation and Research, MAPP 5225.1, Guidance on the Packaging of Test Batches at 1) made by a compounding process, and wherein the levels of, for example, Asp9-bivalirudin, total impurities, and largest unknown impurity, and the reconstitution time represent levels for all potential batches made by said process. " Batches" may also include all batches prepared by a same compounding process.

(See R.119, Claim Construction Order.)

The '727 patent specification describes several experiments Dr. Musso and Dr. Krishna ran and provides the resulting Asp9 impurity levels for the batches produced in each experiment. Examples 4 and 5 in the specification provide a comparison of an old " inefficient" mixing process (Example 4) and a new " efficient" mixing process (Example 5), and Tables 6 and 7 report the impurity levels and reconstitution times for Original Angiomax® batches produced using inefficient mixing (Table 6) and Improved Angiomax® batches produced using efficient mixing (Table 7). (See PTX 397, ¶ ¶ 13-17.)

Comparison of the results in Table 6 ("inefficient mixing") and Table 7 ("efficient mixing") reveals that the percentage of Asp9-bivalirudin impurities in the 24

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reported batches of Improved Angiomax® (shown in Table 7, recreated below) has a lower mean, standard deviation, and a lower maximum level when compared to the 87 reported batches of Original Angiomax® (shown in Table 6, recreated below):

TABLE 6

Characteristics of the batches generated by the compounding

process that features rapid addition of a

pH-adjusting solution and inefficient mixing rates.

No. of batches

Mean / - SD

Maximum

Asp9-bivalirudin (%)

87

0.5 / - 0.4

3.6

Total Impurities (%)

63

1.4 / - 0.5

3.0

Largest unknown impurity (%)

86

0.3 / - 0.1

0.5

Reconstitution Time (seconds)

85

30 / - 12

72

(See PTX 1, col. 22:10-20.)

TABLE 7

Characteristics of the batches generated by the compounding

process that features addition of a

pH-adjusting solution at a constant rate with efficient mixing

No. of batches

Mean / - SD

Maximum

Asp9-bivalirudin (%)

24

0.3 / - 0.1

0.6

Total Impurities (%)

24

1.0 / - 0.4

2.0

Largest unknown impurity (%)

24

0.2 / - 0.1

0.3

Reconstitution Time (seconds)

24

18 / - 6

42

(See id. at col. 23:1-13.) In addition to the 24 reported batches of Improved Angiomax® , the patent specification discloses that Table 7 did not include the results for one batch because " the method used to generate the batch was not compliant with the protocol established for this study." ( See id. at col. 23:14-16.)

II. The Present Litigation

TMC is the owner of New Drug Application (" NDA" ) No. 20-873, which was approved by the U.S. Food and Drug Administration (" FDA" ), on December 15, 2000, for the manufacture and sale of a bivalirudin drug product for intravenous injection. (PTX 397, ¶ 19.) TMC's bivalirudin dug product is marketed in the United States under the tradename Angiomax® . ( Id., ¶ 20.) Bivalirudin is the active ingredient in TMC's Angiomax® drug, which is indicated for use as an anticoagulant during coronary angioplasty and stenting procedures. ( Id., ¶ ¶ 20-24.)

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Mylan submitted Abbreviated New Drug Application (" ANDA" ) No. 202471 to the FDA, seeking approval to engage in the commercial manufacture, use, sale, offer for sale, and/or importation of a generic equivalent to Angiomax® prior to the expiration of the '727 patent. ( See PTX 133; PTX 397, ¶ ¶ 30-31, 34.) The product specification for Mylan's proposed bivalirudin product seeks approval for a bivalirudin drug with Asp9 impurities of up to 2.0% (1.0% a-Asp9 and 1.0% β -Asp9). Mylan submitted an exhibit batch of its proposed bivalirudin product to the FDA in support of its ANDA. Mylan's exhibit batch, CMB10001, had total Asp9 impurities of 0.194%. In November 2011, the FDA sent a deficiency letter to Mylan regarding, among other things, the Asp9 impurity levels provided in Mylan's specification. Specifically, the FDA wrote, " [y]our drug product impurity release specification is wide, and not supported by the exhibit batch test results." ( See PTX 162.) To date, Mylan has not submitted a response to the FDA's deficiency letter. An internal draft response prepared in January 2012, however, proposed changing the maximum Asp9 impurity level to 1.0% (0.5% a-Asp9 and 0.5% β -Asp9). ( See PTX 164.8.)

On February 23, 2011, TMC filed this patent infringement action under the Hatch-Waxman Act, alleging that the manufacture, sale, and offer for sale of Mylan's proposed bivalirudin drug will infringe the '727 patent and United States Patent No. 7,598,343 (the " '343 patent" ). (R.1.) Before trial, the Court granted summary judgment of non-infringement in favor of Mylan with respect to the '343 patent. ( See R.309.) The Court also granted Mylan summary judgment on TMC's willfull infringement claim. ( Id.) The parties proceeded to trial on TMC's infringement claims and Mylan's counterclaims regarding the '727 patent.

The bench trial on the parties' claims regarding the '727 patent lasted approximately six full days. During the trial, the parties admitted numerous exhibits, including the '727 patent file, Mylan's ANDA, and various e-mails and batch testing documents. Additionally, the following witnesses testified at trial:

o Anthony Flammia, Vice President of New Business Ventures for TMC
o Gary Musso, Co-inventor of the '727 patent
o Julie Simon, formerly the Senior Director of Business Development for Mylan
o Daniel Hoch, an employee of Protocol Link, Inc., a consulting firm that assisted Mylan in preparing its bivalirudin ANDA
o Martina O'Sullivan (via videotaped deposition), Director of Regulatory Affairs for Mylan and Bioniche
o Leena Selvaraj (via videotaped deposition), formerly the Director of External Research and Development and Project Management for Bioniche and Mylan
o Malini Sen (via videotaped deposition), Senior Manager of Quality Assurance at Biocon, the drug manufacturer Mylan contracted with to produce Mylan's ANDA exhibit batch.
o Alexander Klibanov, TMC's expert in the fields of chemistry and in pharmaceutical formulations containing peptides, including their stability
o Wayne Talton, Vice President of Global Regulatory Affairs for Mylan
o Ian McKeague, Mylan's expert in statistics

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o David Auslander, Mylan's expert in the field of pharmaceutical formulation and process development
o Rajeshwar Motheram, formerly TMC's Manager of Technical Operations
o Gopal Krishna, Co-inventor of the '727 patent
o Alan Salzberg, TMC's expert in statistics
o Nancy Linck, Mylan's expert in patent prosecution and PTO procedures
o Sandra Kuzmich, TMC's patent prosecution attorney

The parties also submitted deposition designations and videotape clips for the following witnesses: Angela Green; Daniel Robins; James Leary; Lisa-Sue Wood; Pamela Savoy; Russell Garman; Steve McKinnon; and Timothy Smith. During the course of the trial, the Court carefully evaluated the demeanor and credibility of each witness including, where applicable, the witnesses' body language, tone of voice, facial expressions, mannerisms, and other indicative factors. Based on the evidence presented at trial, the Court makes the detailed findings of fact and conclusions of law set forth below.

DISCUSSION

I. Development of the Invention

A. Original Angiomax®

TMC is the owner of NDA No. 20-873, which the FDA approved on December 15, 2000 for the manufacture and sale of a bivalirudin drug product for intravenous injection. (PTX 397, ¶ 19.) TMC's bivalirudin product is marketed under the trade name Angiomax® and among other things, is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. ( Id. ¶ 20.) Anticoagulants are substances that prevent blood from clotting and are commonly used during coronary procedures. ( Id. ¶ ¶ 23-24.)

Bivalirudin is the API in TMC's Angiomax® product that exhibits anticoagulant activity. ( Id. ¶ ¶ 21, 22.) Bivalirudin is a synthetic peptide made up of twenty amino acid residues that are linked in a specific sequence to form a peptide. ( Id. ¶ ¶ 22, 25.) The bivalirudin peptide sequence in Angiomax® is: D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly- Asn -Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu. (PTX 397, ¶ 26 (emphasis added).) The ninth amino acid of the chain, shown above in italics, is asparagine (abbreviated as Asn9 or Asn9). ( Id. ¶ 27.) Under certain conditions, an asparagine (Asn) may decompose (undergo deamidation) to form an aspartic acid (Asp). ( Id. ¶ 28) The impurity " Asp9-bivalirudin," may form in Angiomax® (or a generic equivalent) when the Asn9 residue deamidates to an Asp9 residue. ( Id. ¶ 29.)

Before the inventions of the '727 and '343 patents, the compounding process used to manufacture TMC's Angiomax® drug resulted in variable and sometimes high levels of Asp9 impurities in the final drug product. At least two batches of Angiomax® manufactured using the original compounding process (" Original Angiomax® " ) failed to meet the specification requiring a 1.5% maximum Asp9 impurity level applicable to Original Angiomax® batches. Lot 716184, which TMC's drug manufacturer Ben Venue Laboratories (" Ben Venue" or " BVL" ) produced on June 8, 2005, had an Asp9 impurity level of 3.6%. ( See PTX 223.) Ben Venue investigated the failure of Lot 716184 and determined that laboratory error did not cause the failure. In an attempt to avoid future lot failures, Ben Venue and TMC reviewed and implemented changes to its manufacturing instructions, e.g., instructions for adding the pH-adjusting solution to the bivalirudin

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solution in aliquots. (Tr. 61:22-62:12 (Flammia); Tr. 207:9-208:3 (Musso); PTX 223.15; DTX 1211; DTX 1207; PTX 218 at MEDMYL4399135-36.) Less than a year later, however, Ben Venue produced a second lot with Asp9 impurity levels that again exceeded the 1.5% specification. ( See PTX 218; Tr. 1399:23-1402:22 (Klibanov); Tr. 207:9-2008:25 (Musso); Tr. 62:17-64:22 (Flammia).) The second failed lot, Lot 896002, had an Asp9 impurity level of 2.3%. ( See id.) Ben Venue could not definitively determine the root cause of either lot failure.

Following this second lot failure, TMC decided to become involved with Ben Venue's investigation into the underlying cause of the high Asp9 impurity levels for the failed lot. The co-inventors of the '727 patent, Dr. Gopal Krishna and Dr. Gary Musso, led the investigation for TMC. Dr. Krishna was a TMC employee at the time, and TMC hired Dr. Musso as a consultant to assist in the investigation.

On July 14, 2006, Dr. Musso and two TMC employees, Anthony Flammia and Angie Green, met with several Ben Venue employees involved in the production of Original Angiomax® to discuss the lot failures. Dr. Krishna was on vacation and did not attend the July 14, 2006 meeting. Discussions at the meeting addressed the taffy or marshmallow-like precipitate formed during the compounding process and suggestions on how to improve the process were made. First, variations in the heights of the two stirrers in the tank were proposed so that one stirrer mixes the upper part of the solution and the other mixes the lower part of the solution. ( See PTX 7.) The second proposal involved increasing the stirring speed prior to the addition of the base. ( See id.) Finally, a proposal regarding addition of the base through a dip tube was made, so that the base dispersed at the bottom of the tank where mixing is still possible. ( See id.)

After the operators left the meeting, senior Ben Venue staff and TMC discounted the suggestions. The first suggestion--to vary the stirrer heights--was already part of the Original Angiomax® manufacturing instructions, and Ben Venue had used the third suggestion--adding the base through a dip tube--in manufacturing the first failed lot in 2005. With respect to the second suggestion--increasing the stirring speed before addition of the base--Dr. Musso testified that Ben Venue staff expressed concern that this may lead to foaming.[4]

B. Improved Angiomax®

Following the July 14, 2006 meeting, Dr. Musso and Dr. Krishna observed the compounding process used to manufacture Original Angiomax® and developed a set of experiments designed to identify improvements to reduce the formation of Asp9 impurities during the compounding process. Dr. Musso and Dr. Krishna then supervised and directed the Ben Venue employees who performed the experiments. Ultimately, through these experiments, Dr. Musso and Dr. Krishna developed an " efficient mixing" process that resulted in lower and more consistent Asp9 impurity levels in the bivalirudin final drug product.

Under the direction of Dr. Musso and Dr. Krishna, Ben Venue manufactured 26 batches of Angiomax® using the improved compounding process (" Improved Angiomax® " ). Twenty-four of those batches

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had a maximum Asp9 impurity level of about 0.6% or less, but the remaining two batches had an Asp9 impurity level of 12.4% (Lot 116050) and 1.5% (Lot 1344985). Ben Venue conducted investigations into both failed lots. With respect to Lot 116050, Ben Venue concluded after its investigation that operator error had caused the batch failure. With respect to Lot 1344985, however, Ben Venue found no operator error in the manufacturing process and closed its investigation without identifying the root cause of the failure. TMC and the co-inventors challenged Ben Venue's conclusion that the high Asp9 impurity level in Lot 1344985 was not due to operator error. Ultimately, Ben Venue agreed to destroy the lot and provide a credit to TMC's account for the batch failure. To date, however, neither TMC nor Ben Venue has definitively identified the root cause of the failure.

II. Invalidity

The Court first turns to Mylan's counterclaims that the '727 patent is invalid due to anticipation, obviousness, and non-enablement. Because patents are presumed valid, the party seeking to invalidate a patent--in this case, Mylan--bears the burden of proving the patent's invalidity by clear and convincing evidence. See Microsoft Corp. v. i4i Ltd. P'ship, __ U.S. __, 131 S.Ct. 2238, 2242, 180 L.Ed.2d 131 (2011) (citing 35 U.S.C. § 282). The presumption of validity creates " 'a heavy burden of persuasion,' requiring proof of the defense by clear and convincing evidence.... [T]he presumption encompassed not only an allocation of the burden of proof but also an imposition of a heightened standard of proof." Id., 131 S.Ct. at 2246; see also AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1297-98 (Fed. Cir. 2014) (" [P]atents are presumed to be valid, and overcoming this presumption requires clear and convincing evidence." ). New evidence supporting an invalidity defense that the PTO did not consider before issuing the patent-in-suit may " carry more weight" in an infringement action than evidence that the PTO previously considered. See Microsoft Corp., 131 S.Ct. at 2251. The introduction of new evidence not previously considered by the PTO, however, does not lessen the burden of the party seeking invalidity to prove that the patent is invalid by clear and convincing evidence. Id. at 2250-51.

A. Anticipation Under 35 U.S.C. § 102

Mylan alleges that claims 1-3, 7-10, and 17 of the '727 patent are invalid as anticipated under 35 U.S.C. § 102(b).[5] ( See R.553, Mylan's Post-Trial Brief, at 2-11.)

1. Legal Standard

Section 102(b) provides in relevant part: " A person shall be entitled to a patent unless ... the invention was ... in public use or on sale in this country, more than one year prior to the date of the application for patent in the United States ...." 35 U.S.C. § 102(b); see also ResQNet.com, Inc. v. Lansa, Inc., 594 F.3d 860, 866 (Fed. Cir. 2010) (" An offer for sale, sale, or public use, if more than one year before the patent application was filed, will bar patenting of the product." ). " The on-sale bar applies when two conditions are satisfied before the critical date [i.e. more than one year before the patent was filed]: (1) the claimed invention must be the subject of a commercial offer for sale; and (2)

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the invention must be ready for patenting." Hamilton Beach Brands, Inc. v. Sunbeam Prods., Inc., 726 F.3d 1370, 1374 (Fed. Cir. 2013) (citing Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 67, 119 S.Ct. 304, 142 L.Ed.2d 261 (1998)).

In determining whether claims are invalid due to an on-sale bar, courts should determine " whether the subject of the barring activity met each of the limitations of the claim, and thus was an embodiment of the claimed invention." Netscape Commc'ns Corp. v. Konrad, 295 F.3d 1315, 1323 (Fed. Cir. 2002) (citations omitted). In addition, " [o]nly an offer which rises to the level of a commercial offer for sale, one which the other party could make into a binding contract by simple acceptance (assuming consideration), constitutes an offer for sale under [section] 102(b)." Id (citations omitted). " To determine if the offer is sufficiently definite, one must examine the language of the proposal in accordance with the principles of general contract law." Id. at 1323-24.

2. Analysis

The critical date for the '727 patent is July 27, 2007. ( See PTX 1.) Mylan relies on five Original Angiomax® batches sold in the United States between 2002 and 2004, prior to the critical date, for its § 102(b) argument. Mylan, for example, submitted evidence alleging TMC sold Lot No. 273786 in the United States to Amerisource Bergen Drug Corp. in Louisville, Kentucky (sold on 12/17/02), and to Morris & Dickson Co., LLC in Shreveport, Louisiana (sold on 12/17/02).[6] ( See DTX 1658 at MEDMYL4580643-44; see also JTX 3028 (McKinnon Dep. 126:13-127:10).) Mylan argues that the sales of these batches satisfy the requirements for an on-sale bar, namely, that TMC made the sales before the critical date, and: (1) the sales constitute the claimed invention as a subject of the commercial offer for sale; and (2) the claimed invention was ready for patenting as of that date. TMC argues that the batches to which Mylan refers represent only a subset of the multiple batches of Original Angiomax® and that the Court would have to consider all the batches in its analysis of whether the subject of the commercial offer for sale was in fact the claimed invention.

a. TMC Sold Original Angiomax® Batches Prior to the Critical Date

As an initial matter, TMC does not dispute that the sale of Original Angiomax® batches constitutes a commercial offer for sale and the evidence at trial established the same. During prosecution of Application No. 12/180,553, which issued as the '727 patent, TMC admitted the Original Angiomax® batches referenced in Table 6 were sold, stating " [t]he drug products generated from the old compounding process, which were sold/marketed/offered for sale for more than one (1) year prior to the filing date of the accompanying application, comprised a maximum Asp9-bivalirudin level of about 3.6%, a maximum reconstitution time of about 72 seconds, and a maximum amount of total impurities of about 3.0%." (PTX 3.145 (emphasis added); PTX 3.708-709; see also R.560, TMC's Responsive Post-Trial Br., at 17 (" [T]he file history demonstrates that the PTO was made aware that these Original Angiomax® batches were sold . . . ." ); see also R.418, Pretrial Order, Exhibit M, Mylan's Proposed Findings of Fact and Conclusions

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of Law on Invalidity and Unenforceability and TMC's Responses, TMC's Response to FF.9, stating " [i]n 2001, TMC only sold pharmaceutical batches of Original Angiomax® ." ) The evidence at trial also demonstrated that TMC sold Original Angiomax® , through its distributor--Integrated Commercialization Solutions (" ICS" )--to various customers in the United States prior to July 27, 2007. ( See DTX 1658; DTX 1775; Tr. 150:24-154:9 (Flammia); JTX3028 (McKinnon Dep. 126:13:5-14:17.). The Court, therefore, finds that the Original Angiomax® batches constitute a commercial offer for sale.

b. Original Angiomax® Batches Sold Are Not the Claimed Invention

The Court now turns to whether the commercial offers for sale were of the claimed invention. At their core, Mylan's and TMC's arguments regarding the batches of Original Angiomax® focus on whether a single batch can be used to meet the " pharmaceutical batches" requirement of the '727 patent claims.

During claim construction, the Court construed the term " pharmaceutical batches" as follows:

" Pharmaceutical batches" may include a single batch, wherein the single batch is representative of all commercial batches (see generally, Manual of Policies and Procedures, Center for Drug Evaluation and Research, MAPP 5225.1, Guidance on the Packaging of Test Batches at 1) made by a compounding process, and wherein the levels of, for example, Asp9-bivalirudin, total impurities, and largest unknown impurity, and the reconstitution time represent levels for all potential batches made by said process. " Batches" may also include all batches prepared by a same compounding process.

( See R.119.) Although the parties agreed to this construction during the claim construction hearing, they now disagree on its meaning. TMC argues that the Court's construction consists of two parts: (1) the first part, regarding a " single batch," refers only to an ANDA test batch, as evidenced by the parenthetical citation to MAPP 5225.1 regarding the packaging of test batches, and (2) the second part, regarding " all batches," refers to prior art like Original Angiomax® in which TMC produced multiple batches. Mylan, on the other hand, argues that the first part of the Court's construction regarding a " single batch" may apply to single batches other than ANDA test batches and that the Court should consider whether individual batches of Original Angiomax® on sale before July 27, 2007 anticipate the asserted claims.

The Court need not resolve this dispute, however, because even if the Court accepts Mylan's interpretation, Mylan failed to establish that the individual Original Angiomax® batches on which it relies meet " each of the limitations of the claim, and thus [are] an embodiment of the claimed invention." See Netscape Commc'ns, 295 F.3d at 1323 (citations omitted). Namely, Mylan failed to prove that any of the cited Original Angiomax® batches are " representative" as required by the claim. Namely, that the cited Original Angiomax® batches are: (1) " representative of all commercial batches . . . made by a compounding process," and (2) " wherein the levels of . . . Asp9-bivalirudin ... represent levels for all potential batches made by said process." (PTX 1, claim 1; see also R.119.)

i. TMC Batches 339257 and 515495 Are Not " Representative" of All Commercial Batches

Mylan contends that two of its five cited batches--batches 339257 and 515495--satisfy the " single batch" prong of the Court's

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" pharmaceutical batches" construction because the batches are " representative." Specifically, Mylan argues that TMC's selection of batches 339257 and 515495 as " stability batches" for use in FDA-required testing on the stability, or shelf-life, of its Original Angiomax® drug product demonstrates their " representative" nature. While TMC does not dispute that the batches are from " a compounding process" , it argues that the batches are not " representative" as required by the '727 patent claims. TMC contends that any " representative" nature of the single stability batches identified by Mylan pertains only to their stability, not to the general nature of the batch (which would include being representative of properties other than stability, such as level of impurities.) Both parties, ...


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