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Depomed, Inc. v. Actavis Elizabeth LLC

United States District Court, D. New Jersey

August 25, 2014

DEPOMED, INC., Plaintiff(s),
v.
ACTAVIS ELIZABETH LLC, et al., Defendant(s)

OPINION

JOEL A. PISANO, District Judge.

This is a Hatch-Waxman patent infringement action brought by Plaintiff Depomed, Inc. ("Plaintiff" or "Depomed") against defendants, Actavis Elizabeth LLC and Actavis Inc. (together, "Defendant" or "Actavis") in connection with Defendant's filing of an Abbreviated New Drug Application ("ANDA") seeking approval to sell generic gabapentin once-daily tablets. A bench trial was held May 12, 2014 to May 20, 2014, and the parties presented evidence on the questions of whether Defendant infringes any of the asserted claims in the seven patents-in-suit and whether the asserted claims are obvious and/or indefinite. This Opinion constitutes the Court's findings of fact and conclusions of law. As set forth below, the Court finds that Plaintiff has shown by the preponderance of the evidence that Defendant infringes the asserted claims, and further finds that Defendants have not shown by clear and convincing evidence that the asserted claims are invalid.

A. THE PARTIES

Plaintiff Depomed Inc. is a corporation organized under the laws of California, with a principal place of business in Newark, CA. Final Pretrial Order ("FPO"), Stipulated Facts ("Stip. Facts") ¶1. Depomed, a specialty pharmaceutical company, is the holder of New Drug Application ("NDA") No. 22-544, by which the United States Food and Drug Administration ("FDA") granted approval for tablets containing the active ingredient 1-(aminomethyl) cyclohexaneacetic acid (known as "gabapentin"). Id. ¶ 2; Tr.[1] 373:8. These gabapentin tablets are sold by Depomed in the United States under the brand name Gralise in dosage sizes of 300 mg and 600 mg. Stip. Facts. ¶ 3. Gralise was approved by the FDA for treatment of post-herpetic neuralgia ("PHN"). Id. ¶ 106. Presently, Gralise is the only once-a-day gabapentin product indicated for PHN available in the marketplace that is approved for commercial sale by FDA. Id. ¶ 107. Depomed began selling Gralise in or about October of 2011. Id. ¶ 108.

Defendant Actavis LLC is a limited liability corporation organized and existing under the laws of the State of Delaware, having a place of business in Morristown, New Jersey. Id. ¶ 4. Defendant Actavis Elizabeth LLC is a limited liability company that is wholly owned by Actavis LLC. Id. ¶ 5. Actavis Elizabeth LLC is organized and exists under the laws of the State of State of Delaware, having a principal place of business in Elizabeth, New Jersey. Id. On October 31, 2011, Defendant submitted ANDA No. 203611 with the FDA seeking approval to market generic gabapentin extended-release oral tablets in dosage strengths of 300 mg and 600 mg (the "ANDA product") prior to the expiration of the patents-in-suit. Id. ¶ 14.

B. NATURE OF THE ACTION

The present action is for patent infringement under 35 U.S.C. § 271(e)(2)(A), 271(a), (b), and (c) and under the Hatch-Waxman Act, codified in part at 21 U.S.C. § 355(j). Defendant has counterclaimed for a declaration that it does not and will not infringe any valid claim of the patents-in-suit, and for a declaration that patents-in-suit are invalid.

C. THE PATENTS-IN-SUIT

As set forth below, Depomed asserts against Actavis a number of composition and method claims. These claims are directed to a type of extended-release gabapentin oral dosage form that releases gabapentin in the stomach over several hours and delivers the drug in such a way that an individual achieves certain blood concentrations of the drug and that the drug has a therapeutic effect:

1. Platform/Gastric Retention Patent

a. U.S. Patent No. 6, 635, 280

United States Patent No. 6, 635, 280 (the "280 Patent"), entitled "Extending the Duration of Drug Release Within the Stomach During the Fed Mode, " issued on October 21, 2003, to Depomed from a patent application filed on November 6, 2001, as a continuation from United States Patent No. 6, 340, 475 ("the 475 Patent"). Stip. Facts ¶¶ 8, 50. FDA's publication Approved Drug Products with Therapeutic Equivalence Evaluations (commonly referred to as the "Orange Book") identifies the expiration date of the 280 Patent as September 19, 2016. Id. at ¶ 8.

Depomed has asserted claims 1, 12, 14 and 45 of the 280 Patent in this case.[2] Stip. Facts ¶ 51.

Claim 1 of the 280 Patent is directed to:

A controlled release oral drug dosage form for releasing a drug whose solubility in water is greater than one part by weight of said drug in ten parts by weight of water, said dosage form comprising one or more polymers forming a solid polymeric matrix with said drug incorporated therein at a weight ratio of drug to polymer of from 15:85 to 80:20, said dosage form being one that when swollen in a dimensionally unrestricted manner as a result of imbibition of water is of a size exceeding the pyloric diameter in the fed mode to promote retention in the stomach during said fed mode, that releases said drug into gastric fluid by the dissolution and diffusion of said drug out of said matrix by said gastric fluid, that upon immersion in gastric fluid retains at least about 40% of said drug one hour after such immersion and releases substantially all of said drug after such immersion, and that remains substantially intact until substantially all of said drug is released.

Stip. Facts¶ 53, 280 Patent (JTX 2) at col. 17, ll. 45-61. Claims 12, 14, and 45 depend from claim 1. Claim 12 adds the limitation that the "polymeric matrix is formed of poly(ethylene oxide) at a molecular weight in the range of about 5, 000, 000 to about 8, 000, 000." Stip. Facts. ¶ 59. Claim 14 adds the limitation that the "polymeric matrix upon immersion in gastric fluid retains at least about 60% of said drug one hour after such immersion." Id. at ¶ 60. Claim 45 adds the limitation that the "dosage form releases substantially all of said drug within about ten hours after immersion in gastric fluid." Id. at ¶ 61.

2. Oval/Gastric Retention Patent

a. U.S. Patent No. 6, 488, 962

United States Patent No. 6, 488, 962 (the "962 Patent"), entitled "Tablet Shapes To Enhance Gastric Retention of Swellable Controlled-Release Oral Dosage Forms", issued to Depomed as assignee of the inventors on December 3, 2002, from a patent application filed on June 20, 2000. Stip. Facts ¶¶ 7, 40. The Orange Book identifies the expiration date of the 962 Patent as June 20, 2020. Id. ¶ 7. Plaintiff's product Gralise is an embodiment of the asserted claims of the 962 Patent. Id. ¶ 111.

None of the four asserted claims from this patent have been asserted against Defendant's 300 mg dosage form; claims 5, 8, 10, and 13, from the 962 Patent are being asserted against the 600 mg tablet only. Claims 5, 8, and 10 are dependent upon claim 1. Claim 13 depends from Claim 10.

Independent claim 1 of the 962 patent reads as follows:

A controlled-release oral drug dosage form for releasing a drug into at least a portion of a region defined by the stomach and the upper gastrointestinal tract, said dosage form consisting essentially of a solid monolithic matrix with said drug contained therein, said matrix being non-circular in shape and having first and second orthogonal axes of unequal length, said matrix being one that swells in an unrestricted manner along both such axes upon imbibition of water, the longer such axis having a maximum length of 3.0 cm when said matrix is unswollen, and the shorter such axis achieving a minimum length of 1.2 cm within one hour of immersion of said dosage form in water and wherein said matrix has a shape which when projected onto a plane, is either an oval or a parallelogram.

JTX 1 at col. 11, ll. 14-26, Stip. Facts ¶ 43. Claims 5, 8, and 10 add the following limitations, respectively: (i) the dosage form where the "shorter axis has a length of 0.7 cm to 1.5 cm when said matrix is unswollen"; (ii) the dosage form where the "longer axis has a maximum length of 2.5 cm when said matrix is unswollen"; and (iii) where the "matrix is a water-swellable polymer". JTX 1 at col. 11, ll. 38-39, 47-48 and 53-54; Stip. Facts¶¶ 42, 46-48. Claim 13 depends from claim 10, and adds the following limitation: the dosage form where the "water-swellable polymer is a member selected from the group consisting of poly(ethylene oxide), hydroxypropylmethyl cellulose, and hydroxyethyl cellulose". JTX 1 at col. 12, ll. 2-5; Stip. Facts ¶¶ 42, 49.

3. The Gabapentin Patents [3]

a. U.S. Patent No. 7, 438, 927

United States Patent No. 7, 438, 927 (the "927 Patent"), entitled "Methods of Treatment Using a Gastric Retained Gabapentin Dosage, " issued to Depomed on October 21, 2008, from a patent application filed on October 25, 2002. Stip. Facts ¶¶ 9, 62. The Orange Book identifies the expiration date of the 927 patent as February 26, 2024. Id. ¶ 9. The use of Gralise in treating post-herpetic neuralgia ("PHN") embodies the asserted claims of the '927 Patent. Id. at ¶ 112.

Depomed has asserted claims 18, 25, 26, 34, 61 and 62 of the 927 Patent in this action. Id. ¶ 63. Each of the asserted claims depend from either of two independent claims - claim 17 (claims 18, 25, 26, 61) or claim 33 (claims 26, 62). Neither claim 17 or 33 is asserted in this litigation.

Claim 17 of the 927 Patent is directed to:

A method of treating neuropathic pain in a mammal comprising administering a therapeutically effective amount of a daily dosage of about 100 mg to about 4800 mg of gabapentin or a pharmaceutically acceptable salt thereof, dispersed in a gastric retained dosage form to the mammal in which a fed mode has been induced, wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the mammal, and wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt% of the gabapentin is retained in the dosage form one hour after administration.

JTX 3 at col. 12, ll. 38-51; Stip. Facts ¶ 65.

Asserted claims 18, 25, 26, and 61 depend from claim 17 and, respectively, add the following limitations: (i) the dosage form is administered once daily; (ii) the gastric retained dosage form releases gabapentin to the stomach, duodenum and small intestine; (iii) dosage form provides administration of at least 85 wt % of the gabapentin to be delivered over a period of about 5-12 hours; and (iv) the mammal is a human.

Claim 33 of the 927 Patent reads as follows:

A method of administering a therapeutically effective amount of a daily dosage of about 100 mg to about 4800 mg of gabapentin to a mammal, comprising administering gabapentin or a pharmaceutically acceptable salt thereof, dispersed in a gastric retained dosage form to the mammal in which a fed mode has been induced, and wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the mammal, and wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt% of the gabapentin is retained in the dosage form one hour after administration.

JTX 3 at col. 12, l. 38; col. 13, ll. 25-39; Stip. Facts¶ 70.

Dependent claims 34 and 62, respectively, add the following limitations: (i) the dosage form is administered once daily; and (ii) the mammal is a human. JTX 3 at col. 13, ll. 40-41; col. 14, ll. 50-53; Stip. Facts ¶¶ 71, 72.

b. U.S. Patent No. 7, 731, 989

United States Patent No. 7, 731, 989 (the "989 Patent"), entitled "Gastric Retained Gabapentin Dosage Form, " issued on June 8, 2010, to Depomed from a patent application filed on September 26, 2008, as a continuation of the 927 Patent. Stip. Facts ¶¶ 10, 73. The Orange Book identifies the expiration date of the 989 patent as October 25, 2022. Stip. Facts¶ 10. Gralise is an embodiment of the asserted claims of the '989 Patent. Id. ¶ 113.

Depomed has asserted claim 10 of the 989 Patent in this action. Stip. Facts ¶ 74. Claim 10 depends from claim 1, which has not been asserted. Claim 1 of the 989 Patent reads as follows:

A dosage form, comprising between about 100 mg to about 4800 mg of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single polymer matrix comprising at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in a stomach in a fed mode, wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt % of the gabapentin is retained in the dosage form 1 hour after administration.

JTX 4 at col. 12, ll. 9-18; Stip. Facts¶¶ 75-76. Claim 10 of the 989 Patent contains the additional limitation that "the gabapentin has a bioavailability greater than or equal to 80% of an equal dose of gabapentin in an immediate release dosage form." JTX 4 at col. 12, ll. 37-39; Stip. Facts ¶ 77.

c. U.S. Patent No. 8, 192, 756

United States Patent No. 8, 192, 756 (the "756 Patent"), entitled "Gastric Retained Gabapentin Dosage Form, " issued on June 8, 2010, to Depomed from a patent application filed on May 19, 2011, as a continuation of the 927 Patent, Stip. Facts ¶¶ 11, 78, and claims the same priority date of October 25, 2001, JTX3 at 1. Depomed has asserted claims 1, 2, 5, 6, 7 and 11 of the 756 Patent in this action. Stip. Facts¶ 79. The Orange Book identifies the expiration date of the 756 patent as October 25, 2022. Gralise or its use in treating PHN embodies the asserted claims of the '756 Patent. Id. ¶ 114.

Claim 1 of the 756 Patent is directed to:

A dosage form, comprising:

comprising from 100 mg to 4800 mg of therapeutically effective amount of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single matrix
wherein the matrix comprises at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach in a fed mode,
wherein upon once-daily or twice-daily ingestion of the dosage form gabapentin is released from the matrix over a period of at least five hours wherein at least 40 wt% of the gabapentin is retained in the matrix one hour after administration, and
wherein the gabapentin is released at a rate sufficient to achieve a lower maximum plasma concentration (Cmax) compared to an equal dose of gabapentin provided by an immediate release dosage form, and without loss in bioavailability as measured by the area under the curve (AUCinfinity) as compared to the bioavailability which is achieved from an immediate release dosage form comprising the same dose of gabapentin.

JTX 5 at col. 12, l. 50-col. 13, l. 3; Stip. Facts¶ 81.

Claims 2 and 5 depend from claim 1, and add the following limitations: (i) the time to reach maximum plasma concentration is longer relative to the time to reach maximum plasma concentration from an immediate release dosage form comprising the dose of gabapentin; and (ii) the dosage form comprises a dose of gabapentin of between about 300-600 mg. JTX 5 at col. 13, ll. 4-7, 12-13; Stip. Facts¶¶ 83, 84.

Claim 6 of the 756 Patent is similar to claim 1, however it is directed to a method of treating a condition using the gabapentin-containing dosage form:

A method of treating a condition responsive to a therapeutic dose of gabapentin, comprising:
orally administering once-daily or twice daily a dosage form comprising between about 100 mg to about 4800 mg of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single matrix,
wherein the matrix comprises at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach in a fed mode, wherein upon once-daily or twice daily ingestion of the dosage form gabapentin is released from the matrix over a period of at least five hours wherein at least 40 wt% of the gabapentin is retained in the matrix one hour after administration, and
whereby the dosage form releases gabapentin at a rate sufficient to achieve a lower maximum plasma concentration (Cmax) compared to an equal dose of gabapentin provided by an immediate release dosage form, and without loss in bioavailability as measured by the area under the curve (AUCinfinity) as compared to the bioavailability which is achieved from an immediate release dosage form comprising the same dose of gabapentin.

JTX 5 at col. 13, ll. 14-38.

Claim 7 and 11 depend from claim 6, and add the following limitations: (i) the time to reach maximum plasma concentration is longer relative to the time to reach maximum plasma concentration from an immediate release dosage form comprising the dose of gabapentin; and (ii) the condition is neuropathic pain. JTX 5 at col. 14, ll. 1-4, 10-11.

d. U.S. Patent No. 8, 252, 332

United States Patent No. 8, 252, 332 (the "332 Patent"), entitled "Gastric Retained Gabapentin Dosage Form, " issued on August 28, 2012, to Depomed from a patent application filed on March 29, 2010, as a continuation of the 927 Patent. Stip. Facts ¶¶ 12, 88. Depomed has asserted claims 1, 6, 17, 22 and 24 of the 332 Patent. The Orange Book identifies the expiration date of the '332 Patent as October 25, 2022. Id. ¶ 12. Gralise or its use in treating PHN embodies the asserted claims of the 332 Patent. Id. ¶ 115.

Claim 1 of the '332 Patent reads as follows:

A dosage form, comprising a matrix comprising gabapentin, wherein upon ingestion of the dosage form gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a lower maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasma concentration-time curve, AUCinf·

JTX 6 at col. 12, ll. 12-22.

Claim 6 depends from claims 1, 4, and 5. Claim 4 is directed to "[t]he dosage form of claim 1, wherein the matrix is a polymer matrix." JTX 6 col 12, ll. 27-28. Claim 5 is directed to "[t]he dosage form of claim 4, wherein the polymer matrix is comprised of a swellable, hydrophilic polymer." Id. ll. 29-30. Claim 6 is directed to "[t]he dosage form of claim 5, wherein the gabapentin is released from the polymer matrix by diffusion." Id. ll. 31-32.

Asserted claim 17 is a method claim which depends from claim 12. Claim 12 of the 332 patent reads as follows:

A method of treating a condition responsive to a therapeutic dose of gabapentin, comprising: orally administering a dosage form, comprising a matrix comprising gabapentin, wherein upon ingestion of the dosage form gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a lower maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasmaconcentration-time curve, AUCinf.

JTX6 at col 12, ll. 53-65. Claim 17 adds the limitation that the "condition is neuropathic pain." Id. col. 13, ll. 6-7.

Claim 22 of the 332 Patent is directed to:

A dosage form, comprising a matrix comprising gabapentin, wherein upon ingestion of the dosage form gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a longer time to the maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasma concentration-time curve, AUCinf.

JTX 6 at col. 13, l. 21-col. 14, l. 2.

Claim 24 of the 332 Patent is directed to:

A method of treating a condition responsive to a therapeutic dose of gabapentin, comprising orally administering a dosage form comprising a matrix comprising gabapentin, wherein gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a longer time to the maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasma concentration-time curve, AUCinf.

JTX 6 at col. 14, ll. 16-29.

e. U.S. Patent No. 8, 333, 992

The 992 Patent, entitled "Gastric Retained Gabapentin Dosage Form, " issued on December 18, 2012, to Depomed from a patent application filed on July 27, 2012, as a continuation of the 927 Patent. Stip. Facts ¶¶ 13, 99. The Orange Book identifies the expiration date of the 992 Patent as October 25, 2022. Id. ¶ 13. Gralise or its use in treating PHN embodies the asserted claims is an embodiment of the '992 Patent. Id. ¶ 116.

Depomed has asserted claims 1, 5 and 22 of the 992 Patent in this action. Stip. Facts¶ 100.

Claim 1 of the 992 Patent is directed to:

A dosage form, comprising a matrix comprising gabapentin, wherein upon ingestion of the dosage form by a human subject gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a lower maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasma concentration-time curve, AUCinf.

JTX 7 at col. 12, ll. 40-51; Stip. Facts ¶ 102.

Claim 5 depends from claim 4, which in turn depends from claim 1. Claims 4 and 5, respectively, add the limitations "wherein the matrix is a polymer matrix" and "wherein the polymer matrix is comprised of a swellable, hydrophilic polymer." JTX 7 at col. 12, ll. 56-59.

Asserted Claim 22 of the 992 Patent reads as follows:

A method of treating a condition responsive to a therapeutic dose of gabapentin, comprising: orally administering to a human subject a dosage form comprising a matrix comprising gabapentin, wherein gabapentin is released from the matrix into the upper gastrointestinal tract over about 5-12 hours at a rate sufficient to achieve a longer time to the maximum plasma concentration than that provided by an immediate release dosage form comprising an equal amount of gabapentin, and bioavailability of gabapentin is at least 80% of that provided by the immediate release dosage form comprising an equal amount of gabapentin as measured by the area under the plasma concentration-time curve, AUCinf.

JTX 7 at col. 14, ll. 13-26.

D. WITNESSES AT TRIAL

The trial commenced with Plaintiff's infringement case. For its infringement case-in-chief, Depomed called five expert witnesses, Dr. Eden Tesfu, Dr. Gary Annunziata, Dr. Hartmut Derendorf, Dr. Robert O. Williams, and Dr. Howard Hopfenberg.

Dr. Eden Tesfu, a former laboratory manager at Evans Analytical Life Sciences, was accepted by the Court as an expert in analytical chemistry. Tr. 92:19-22. Dr. Tesfu testified regarding swelling and dissolution studies performed on the Defendants' proposed ANDA product and Plaintiff's Gralise tablet. Tr. 89-134.

Dr Gary Annunziata, a practicing gastroenterologist at the Eisenhower Medical Center, Palm Springs, California, was accepted by the Court as an expert in stomach physiology. Tr. 148:12-14. Dr. Annunziata testified with respect to the human pylorus and the process of stomach digestion and emptying. Tr. at 141-168, 207-260.

Dr. Hartmut Derendorf, a professor of pharmaceutics at the University of Florida, was accepted as an expert in the field of pharmacokinetics by the Court. Tr. at 336:5-8. Dr. Derendorf testified on the pharmacokinetic data from the Actavis ANDA and evidence for gastric retention. Tr. at 332-367. Dr. Derendorf also provided testimony with respect to the issue of obviousness. Tr. at 1022-1061.

Dr. Robert O. Williams, a professor at the University of Texas and a registered pharmacist in the State of Texas, was accepted by the Court as an expert in the field of formulation and pharmaceutical sciences. Tr. at 264:4-7. Dr. Williams testified as to the ingredients and swelling properties of the proposed ANDA product and Gralise tablets. Tr. at 260-309.

Dr. Harold Hopfenberg, a professor of chemical and biomolecular engineering at North Carolina State University, was accepted by the Court as an expert in polymer science and controlled release dosage forms. Tr. at 437:13-19. Dr. Hopfenberg testified as to the shape and swelling of the Actavis ANDA product. Tr. at 431-494. Dr. Hopfenberg also testified with respect the obviousness issues relating to the 962 Patent in Depomed's response case. Tr. at 931-955.

Plaintiff also presented the testimony of three fact witnesses with respect to the issue of infringement, Mr. Jack Lee Anders, VP of Finance for Depomed Inc., Dr. Radi Hejazi, Formulation Scientist at Actavis Elizabeth, and Dr. Meena Venugopal, former employee at Actavis.

In response to Plaintiff's infringement case, Defendant called one expert witness, Dr. David Friend, director of product development at the CONRAD Program and associate research professor of obstetrics and gynecology at Eastern Virginia Medical School. Dr. Friend was accepted as an expert in the design and development of controlled release dosage forms, design and development of gastric retained dosage forms, behavior of dosage forms in the stomach during fed mode and the sizes and shapes of oral dosage forms. Tr. 498:9-12, 502:3-504:10. Dr. Friend testified as to the shape and swelling of Defendant's ANDA tablets. Tr. 497-547.

The trial then proceeded to the issue of validity. Defendant's obviousness case-in-chief was presented through two expert witnesses, Dr. Douglas Flanagan and Dr. Michael Mayersohn, along with a fact witness by way of deposition testimony, inventor Dr. Sui Yuen Eddie Hou (by video), a former Depomed employee and one of the named inventors of the Gabapentin Patents.

Dr. Douglas R. Flanagan, a professor emeritus of pharmacy of the University of Iowa and the chief scientific officer for the University of Iowa's Pharmaceuticals Development Consortium, was accepted as an expert in pharmaceutical formulation, including the design and development of controlled release dosage forms. Tr. 549:20-22, 552:10-14. Dr. Flanagan provided testimony on the issue of obviousness with respect to all of the Gabapentin Patents (927, 989, 756, 332, 992 Patents). Tr. 549-578, 608-687.

Dr. Michael Mayersohn, a professor of pharmaceutical sciences at the University of Arizona, College of Pharmacy, was accepted as an expert on drug absorption and pharmacokinetics. Tr. 688:14-15, 692:6-10. Dr. Mayersohn testified on the issue of obviousness with respect to two of the Gabapentin Patents, the 332 and 992 Patents. Trial Tr. 688-742.

In its response to Defendant's obviousness case, Plaintiffs called experts Dr. Howard Bockbrader, Dr. Barry Gidal, Dr. Michelle Brown, Dr. Howard Hopfenberg, Dr. Linda Felton, Dr. Hartumut Derendorf, and Dr. Sean Nicholson. Plaintiff also presented testimony by deposition of Dr. Andrew Johnson, Analytical Scientist for Actavis, regarding his role in the development of the ANDA product. Tr. 1138:2-8.

Dr. Howard Bockbrader was accepted by the Court as an expert in the area of clinical pharmacokinetics and in particular the pharmacokinetics of gabapentin. Trial Tr. 748:8-13. Dr. Bockbrader testified with respect to Warner-Lambert efforts to develop an extended release gabapentin product and its opinion as to whether a gastric retained gabapentin product could be developed. Tr. at 743-777. His testimony related to the 927, 989, 756, 332 and 992 Patents.

Dr. Barry Gidal was accepted by the Court as an expert on gabapentin pharmacokinetics and pharmacodynamics. Trial Tr. 815:14-816:2. Dr. Gidal testified on issues related to whether it was possible to develop a controlled-release gabapentin tablet. Tr. at 811-865. His testimony related to the Gabapentin Patents.

Dr. Michelle Brown was accepted by the Court as an expert in the area of treating neuropathic pain. Tr. at 869:4-20. Dr. Brown testified on the issue of long felt need for a controlled-release gabapentin product and the manner in which Gralise is prescribed. Trial Tr. at 866-893. Her testimony related to the Gabapentin Patents.

Dr. Linda Felton was accepted by the Court as an expert in controlled-release dosage forms. Tr. at 959:1-4. Dr. Felton testified regarding non-obviousness of a controlled-release gabapentin tablet. Tr. at 955-1021. Her testimony related to the Gabapentin Patents.

Dr. Sean Nicholson was accepted by the Court as an expert in the field of economics in healthcare. Tr. at 1064:5-7. Dr. Nicholson testified as to his evaluation of the commercial success of the Gralise product, the 962 Patent and the Gabapentin Patents. Tr. at 1061-1099.

In rebuttal, Defendant called two expert witnesses, Dr. Raymond Sinatra and Dr. Ryan Michael Sullivan.

Dr. Raymond Sinatra was accepted by the Court as an expert in pain medicine and the prescribing practices of physicians in pain management. Tr. At 895:21-24. Dr. Sinatra testified as to clinical trials performed on Gralise. Tr. at 893-908.

Dr. Ryan Michael Sullivan was accepted by the Court as an expert in the economics of intellectual property as it pertains to pharmaceutical products. Tr. at 1165:25-1166:5. Dr. Sullivan testified as to his evaluation of the commercial success of Gralise. Tr. at 1164-1201.

E. INFRINGEMENT

1. Legal Standards

If an ANDA seeks approval for a drug that is claimed in a patent or the use of which is claimed in a patent, submission of the ANDA constitutes a statutory act of infringement pursuant to § 271(e)(2) of the Patent Act. This section provides:

It shall be an act of infringement to submit an application under [section 355(j) of title 21]... for a drug claimed in a patent or the use of which is claimed in a patent... if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use, or sale of a drug, veterinary biological product, or biological product claimed in a patent or the use of which is claimed in a patent before the expiration of such patent.

35 U.S.C. § 271(e)(2)(A). In order make the infringement determination, a court conducts a two-step infringement inquiry. First, the court construes the claims of the patent. Second, the court compares the construed claims to the accused product and makes a determination as to whether every claim limitation, or its equivalent, is found in the accused product. Roche Palo Alto LLC v. Apotex, Inc., 531 F.3d 1372, 1377 (Fed. Cir. 2008). In the ANDA context, the proper infringement inquiry focuses on the actual product that will enter the market upon FDA approval. Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 1569 (Fed. Cir. 1997) (court "must focus on what the ANDA applicant will likely market if its application is approved"); Ben Venue Labs. v. Novartis Pharm. Corp., 146 F.Supp.2d 572, 579 (D.N.J. 2001) ("the statute requires that an infringement inquiry be focused on what is likely to be sold following FDA approval").

To prove infringement, the patentee must show that an accused product or method is within the claim limitations of the patent-in-suit either literally or under the doctrine of equivalents. See Amgen Inc. v. F. Hoffmann-LaRoche Ltd., 580 F.3d 1340, 1374 (Fed. Cir. 2009); Warner Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 U.S. 17, 21 (1997).

Direct infringement requires a party to perform each and every step or element of a claimed method or product. Cheese Systems, Inc. v. Tetra Pak Cheese and Powder Systems, Inc., 725 F.3d 1341, 1348 (Fed. Cir. 2013). "If any claim limitation is absent from the accused device, there is no literal infringement as a matter of law." Bayer AG v. Elan Pharm. Research Corp., 212 F.3d 1241, 1247 (Fed. Cir. 2000). If an accused product does not infringe an independent claim, it also does not infringe any claim depending thereon. See Wahpeton Canvas Co. v. Frontier, Inc., 870 F.2d 1546, 1553 (Fed. Cir. 1989).

Induced infringement, on the other hand, "requires that the alleged infringer knowingly induced infringement and possessed specific intent to encourage another's infringement." DSU Med. Corp. v. JMS Co., 471 F.3d 1293, 1306 (Fed. Cir. 2006). The induced infringement provision of the Patent Act, 35 U.S.C. § 271(b), provides that "[w]hoever actively induces infringement of a patent shall be liable as an infringer." "[T]he sale of a product specifically labeled for use in a patented method constitutes inducement to infringe that patent, and usually is also contributory infringement." Eli Lilly & Co. v. Actavis Elizabeth LLC, 435 Fed.App'x 917, 926 (Fed. Cir. 2011) (citing Astrazeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed. Cir. 2010); DSU Med. Corp., 471 F.3d at 1305-06.

Thus, induced infringement under § 271(b) occurs where: (1) another party directly infringes a patent claim; (2) the inducing party intentionally encourages the acts that constitute such direct infringement; and (3) the inducing party knows that its actions will cause direct infringement. See Global-Tech Appliances, Inc. v. SEB S.A., 131 S.Ct. 2060, 2068 (2011); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1312 (Fed. Cir. 2005). To prove indirect infringement by the manufacturer of an allegedly infringing product, a patentee must show that the manufacturer's customers directly infringe the patent. See Glenayre Elecs., Inc. v. Jackson, 443 F.3d 851, 858 (Fed. Cir. 2006). Induced infringement under 35 U.S.C. § 271(b) requires knowledge that the induced acts constitute patent infringement. See Global-Tech, 131 S.Ct. at 2068.

Contributory infringement occurs if a party sells or offers to sell, a material or apparatus for use in practicing a patented process, and that "material or apparatus" is material to practicing the invention, has no substantial non-infringing uses, and is known by the party "to be especially made or especially adapted for use in an infringement of such patent." 35 U.S.C. § 271(c). Contributory infringement exists where "it may be presumed from distribution of an article in commerce that the distributor intended the article to be used to infringe another's patent, and so may justly be held liable for that infringement." Metro-Goldwyn-Mayer Studios Inc. v. Grokster, Ltd., 545 U.S. 913, 932 (2005).

To establish contributory infringement, the patent owner must prove that: "(1) there is direct infringement; (2) the accused infringer had knowledge of the patent at issue; (3) the component has no substantial noninfringing uses; and (4) "the component is a material part of the invention." See Fujitsu Ltd. v. Netgear Inc., 620 F.3d 1321, 1326 (Fed. Cir. 2010).

An accused infringer's knowledge of the patents may be demonstrated by an ANDA filer's certification and Notice Letter to the patent holder. Teva Pham. U.S.A., Inc. v. Sandoz, Inc., 876 F.Supp.2d 295, 349 (S.D.N.Y 2012).

In assessing whether an asserted noninfringing use is substantial, the factfinder considers not only the use's frequency, but also the use's practicality, the invention's intended purpose, and the intended market. i4i Ltd. P'ship v. Microsoft Corp., 598 F.3d 831, 851 (Fed. Cir. 2010) aff'd, 131 S.Ct. 2238 , 180 L.Ed.2d 131 (2011). A substantial non-infringing use is one that is "not unusual, farfetched, illusory, impractical, occasional, aberrant, or experimental." Vita-Mix Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1327 (Fed. Cir. 2009).

Plaintiff bears the burden of proving infringement and must meet its burden by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988).

2. Direct Infringement

a. The 927, 989, and 756 Patents

Plaintiff alleges direct, literal infringement of the 927, 989, and 756 Patents. With respect to infringement of these patents, there is a single claim element that is in dispute, specifically, "swells... to increase its size to promote gastric retention." The Court has construed this claim element, which appears in several of the asserted patents, to mean "such that when the dosage form is introduced into the stomach in the fed mode, the dosage form remains in the stomach for several hours." D.I. 251 at 6-11. Claims 18, 25, 26, 34, 61 and 62 of the 927 Patent, claims 1, 2, 5, 6, 7 and 11 of the 756 Patent and claim 10 of the 989 Patent each contain this claim element. Tr. 519:13-520:25. The Court finds that Plaintiff has established by the preponderance of the evidence that Defendant's ANDA product meets this limitation.

As an initial matter, the proposed ANDA products use hydrophilic polymers known to swell in gastric fluid. Indeed, the proposed ANDA labeling states that the gabapentin tablets swell in gastric fluid and gradually release gabapentin. Tr. 457:16-18; PTX000136. ACTGAB000321121. According to the label, the ANDA products contain [REDACTED/] Tr. 163:4-17; PTX000136, ACTGAB000321121. They [REDACTED/]Tr. 271:17-22; PTX000014, ACTGAB000000330. [REDACTED/]hydrophilic, i.e., "water loving", and are known to absorb water and swell. Tr. 458:5-23; see also Tr. 270:10-271:8; PTXO-136, ACTGAB000321121. Thus, the tablets swell in gastric fluid and contain ingredients that are swellable or imbibe water. Tr. 163:4-17; 238:18-239:3.

Second, the ANDA products use similar swellable polymers in similar amounts as Gralise tablets, which are embodiments of the asserted claims. See PTX000014 at ACTGAB000000330. [REDACTED/] according to Dr. Williams, are considered to be enabling of diffusion controlled release from a tablet dosage form. Tr. 271:17-22; 273:1-9. The higher the molecular weight of the polymer used in a ...


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