Vanda Pharm. Inc. v. Roxane Labs., Inc.

203 F.Supp.3d 412

VANDA PHARMACEUTICALS INC. and Aventisub LLC, Plaintiffs,

v.ROXANE LABORATORIES, INC., Defendant.

Civil Action No. 13-1973-GMS

Civil Action No. 14-757-GMS

United States District Court, D. Delaware.

Signed August 25, 2016

Jack B. Blumenfeld, Karen Jacobs, Morris, Nichols, Arsht & Tunnell LLP, Wilmington, DE, Eric A. Stone, Josephine Young, Kira A. Davis, Nicholas Groombridge, Pro Hac Vice, for Plaintiffs.

Richard L. Horwitz, Bindu Ann George Palapura, David Ellis Moore, Potter Anderson & Corroon, LLP, Wilmington, DE, Emily C. Melvin, Kenneth G. Schuler, Michael R. Seringhaus, Timothy J. O'Brien, Pro Hac Vice, for Defendant.

MEMORANDUM

GREGORY M. SLEET, UNITED STATES DISTRICT JUDGE

I. INTRODUCTION

In this consolidated patent infringement action, plaintiffs Vanda Pharmaceuticals Inc. ("Vanda") and Aventisub LLC ("Aventisub") (collectively "the Plaintiffs") allege infringement by Roxane of U.S. Reissue Patent No. 39,198 ("the '198 Patent") and U.S. Patent No. 8,586,610 ("the '610 Patent"). The two actions were consolidated for purposes of trial on April 13, 2015. The court held a five-day bench trial in this matter on February 29, 2016 to March 4, 2016. (D.I. 171–176.) Presently before the court are the parties' post-trial proposed findings of fact and post-trial briefs concerning the validity of the patents-in-suit and whether Roxane's proposed products infringe the '610 Patent. (D.I. 178, 179, 184, 185.)

Pursuant to Federal Rule of Civil Procedure 52(a), and after having considered the entire record in this case and the applicable law, the court concludes that: (1) all asserted claims of the patents-in-suit are valid; (2) Roxane's proposed products induce infringement of the asserted claims of the '610 Patent ; (3) Roxane's proposed products do not contributorily infringe the asserted claims of the '610 Patent ; and (4) each of the parties' Rule 52(c) motions are granted in part and denied in part. These findings of fact and conclusions of law are set forth in further detail below.¹

II. FINDINGS OF FACT²

A. The Parties

1. Plaintiff Vanda is a Delaware corporation with its principal place of business at 2200 Pennsylvania Ave NW, Washington, DC 20037.

2. Plaintiff Aventisub is a Delaware corporation with its principal place of business at 3711 Kennett Pike, Suite 200, Greenville, DE 19807.

3. Defendant Roxane is a Nevada corporation with its principal place of business at 1809 Wilson Road, Columbus, OH 43228.

4. The court has subject matter jurisdiction as well as personal jurisdiction over all parties.

B. Background

5. Genotyping assays are currently commercially available to identify CYP2D6 poor metabolizers.

6. Genotyping assays are laboratory tests.

7. The generic iloperidone described in the Roxane AND A is literally within the scope of claim 3 of the '198 Patent and infringes claim 3 of the '198 Patent provided that the claim is not proved invalid.

8. Extrapyramidal side effects ("EPS") are undesired side effects of antipsychotic medications.

9. Atypical antipsychotics have fewer extrapyramidal side effects than typical antipsychotics.

C. The Patents-in-Suit

10. The '198 Patent, entitled "Heteroarylpiperidines, Pyrrolidines and Piperazines and Their Use as Antipsychotics and Analgesics," issued on July 18, 2006, and names Joseph T. Strupczewski, Grover C. Helsley, Yulin Chiang, Kenneth J. Bordeau, and Edward J. Glamkowski as the inventors.

11. The '198 Patent was filed on November 15, 2000, and is a reissued patent of U.S. patent no. 5,364,866, filed on October 30, 1992.

12. The '198 Patent claims priority to U.S. Patent Application No. 07/354,411, filed on May 19, 1989.

13. The '198 Patent expires on November 15, 2016.

14. Aventisub is the owner by assignment of the '198 Patent.

15. Vanda holds an exclusive worldwide license to the '198 Patent.

16. The '610 Patent, entitled "Methods for the Administration of Iloperidone," issued on November 19, 2013, and names Curt D. Wolfgang and Mihael H. Polymeropoulos as the inventors.

17. The '610 Patent claims priority to U.S. Provisional Application No. 60/614,798, filed on September 30, 2004.

18. The '610 Patent expires on November 2, 2027.

19. Vanda is the owner by assignment of the '610 Patent.

20. Vanda has standing to sue for infringement of the '610 Patent.

1. The Asserted Claims

a. '198 Patent, Claim 3

Claim 3 of the '198 Patent reads:

A compound as claimed in claim 1, which is 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]ethanone or a pharmaceutically acceptable acid addition salt thereof. The nonproprietary name for l-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]ethanone is "iloperidone."

b. '610 Patent, Claims 1-9, 11-13, and 16

Claims 1-9, 11-13, and 16 of the '610 Patent read:

A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of: determining whether the patient is a CYP2D6 poor metabolizer by: obtaining or having obtained a biological sample from the patient; and performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day, wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.

2. The method of claim 1, wherein the performing or having performed the genotyping assay step comprises: extracting or having extracted genomic DNA or mRNA from the biological sample, and sequencing or having sequenced CYP2D6 DNA derived from the extracted genomic DNA or from the extracted mRNA, wherein the sequencing or having sequenced step further comprises: amplifying or having amplified a CYP2D6 region in the extracted genomic B-2 DNA or mRNA to prepare a DNA sample enriched in DNA from the CYP2D6 gene region; and sequencing or having sequenced the DNA sample by hybridizing the DNA sample to nucleic acid probes to determine if the patient has a CYP2D6 poor metabolizer genotype; and wherein the CYP2D6 poor metabolizer genotype is one of the CYP2D6G1846A genotype or the CYP2D6C100T genotype.

3. The method of claim 2, wherein the CYP2D6 poor metabolizer genotype is one of the CYP2D6G1846A (AA) genotype or the CYP2D6G1846A (AG) genotype.

4. The method of claim 3, wherein the CYP2D6 poor metabolizer genotype is the CYP2D6G1846A (AA) genotype.

5. The method of claim 2, wherein the CYP2D6 poor metabolizer genotype is one of the CYP2D6C100T (TT) genotype or the CYP2D6C100T (CT) genotype.

6. The method of claim 5, wherein the CYP2D6 poor metabolizer genotype is the CYP2D6C100T (TT) genotype.

7. The method of claim 1, wherein the step of internally administering iloperidone to the patient in an amount of 12 mg/day or less comprises internally administering iloperidone to the patient in an amount of 6 mg or less b.i.d.

8. The method of claim 2, wherein, if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 6 mg b.i.d.

9. A method of treating a patient who is suffering from a schizoaffective disorder, depression, Tourette's syndrome, a psychotic disorder or a delusional disorder, the method comprising: determining if the patient is a CYP2D6 poor metabolizer by obtaining or having obtained a biological sample from the patient, and performing or having performed a genotyping assay on the biological sample to determine whether the patient has a CYP2D6 poor metabolizer genotype, and if the patient is a CYP2D6 poor metabolizer, then internally administering iloperidone to the patient in an amount of up to 12 mg/day, and if the patient is not a CYP2D6 poor metabolizer, then internally administering iloperidone to the patient in an amount of greater than 12 mg/day, up to 24 mg/day.

11. The method of claim 9, wherein the CYP2D6 poor metabolizer genotype is one of: B-3 CYP2D6G1846A (AA), CYP2D6G1846A (AG), CYP2D6C100T (TT), or CYP2D6C100T (CT).

12. The method of claim 9, wherein the method comprises: if the patient is a CYP2D6 poor metabolizer, then internally administering the iloperidone to the patient in an amount of 6 mg b.i.d.

13. A method of treating a patient who is suffering from a schizoaffective disorder, depression, Tourette's syndrome, a psychotic disorder or a delusional disorder, the method comprising: determining if the patient is at risk for iloperidone-induced QTc prolongation by obtaining or having obtained a biological sample from the patient, and performing or having performed a genotyping assay on the biological sample to determine whether the patient has a CYP2D6 poor metabolizer genotype, wherein the presence of a CYP2D6 poor metabolizer genotype indicates risk for iloperidone-induced QTc prolongation, and if the patient is at risk for iloperidone-induced QTc prolongation, then internally administering iloperidone to the patient in an amount of up to 12 mg/day, and if the patient is not at risk for iloperidone-induced QTc prolongation, then internally administering iloperidone to the patient in an amount of greater than 12 mg/day, up to 24 mg/day.

16. The method of claim 13, wherein the method comprises: if the patient is at risk for iloperidone-induced QTc prolongation, then internally administering the iloperidone to the patient in an amount of 6 mg b.i.d. claims 1-9, 11-13, and 16 of the '610 Patent.

D. FANAPT® and Roxane's ANDA

20. FANAPT® (iloperidone) is an atypical antipsychotic approved for the treatment of patients with schizophrenia. Vanda...