Paper Date: 5 March 2013 UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD

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1 Paper Date: 5 March 2013 UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD RANBAXY LABORATORIES, LTD. AND RANBAXY, INC. Petitioner v. VERTEX PHARMACEUTICALS, INC. Patent Owner Case IPR (SGL) Before SALLY GARDNER LANE, RAE LYNN P. GUEST, and DEBORAH KATZ Administrative Patent Judges. GUEST, Administrative Patent Judge. DECISION Institution of Inter Partes Review 37 C.F.R

2 BACKGROUND Petitioner Ranbaxy Laboratories, Ltd. and Ranbaxy, Inc. (hereinafter Petitioner ) requests inter partes review of claims 1-12 of U.S. (hereafter 989 Patent ) pursuant to 35 U.S.C. 311 et seq. (Paper 1 (hereinafter Pet. ).) The Patent Owner, Vertex Pharmaceuticals, Inc. (hereinafter Patent Owner ), filed a preliminary response under 37 C.F.R (a). (Paper 23 (hereinafter Prelim. Resp. ).) We have jurisdiction under 35 U.S.C The standard for instituting inter partes review is set forth in 35 U.S.C. 314(a), which provides: THRESHOLD -- The Director may not authorize an inter partes review to be instituted unless the Director determines that the information presented in the petition filed under section 311 and any response filed under section 313 shows that there is a reasonable likelihood that the petitioner would prevail with respect to at least 1 of the claims challenged in the petition. We determine that the Petition demonstrates that there is a reasonable likelihood that Petitioner would prevail with respect to claims Therefore, we authorize an inter partes review to be instituted as to claims 1-12 of the 989 patent. Related Proceeding Petitioner indicates that the 989 patent is asserted in a co-pending litigation styled ViiV Heathcare Co. v. Mylan, Inc., Case No RGA (D. Del.). (Pet. 2). It is asserted that Petitioner is not party to the ongoing litigation. (Id.) DISCUSSION The Invention of the 989 Patent The 989 Patent is directed to prodrugs of HIV aspartyl protease inhibitors, pharmaceutical compositions thereof, and methods of treating mammals therewith. 2

3 ( 989 Patent, col. 1, ll ) Prodrugs are generally inactive compound that converts to an active drug in the body. Usually, a prodrug has some improved pharmacological property over the active drug, such as improved stability or solubility. (See 989 Patent, col. 2, ll. 7-16, col. 33, ll ) The prodrugs of the 989 Patent are said to have favorable aqueous solubility, to have high oral bioavailability and facile in vivo generation of the active ingredient, and to be particularly well suited for decreasing pill burdenn and increasing patient compliance. ( 9899 Patent, col. 1, ll ) The relevant compound of the 989 Patentt is a prodrug of a known HIV aspartyl protease inhibitor commonly referred too as VX-478. ( 989 Patent, col. 1, ll ; col. 30, l. 29- col. 34, l. 67.) VX-478 has the following structure ( 989 Patent, col. 30, l. 32; col. 31, l. 5). Examples 27 to 30 detail the process for forming phosphate ester derivedd prodrugs of VX-478. ( 989 Patent, col. 57, l. 1 col. 60, l.. 14.) Example 30, in particular, describes a disodium phosphate ester salt prodrug of VX-478. ( 9899 Patent, col. 59, ll and col. 60, ll ) Claims 1-4 and 9 are reproduced d below: 1. A compound of the formula: 3

4 wherein: R 7 is selected from -PO 2-3 Na 2+, -PO 2-3 K 2+, -PO 2-3 Mg 2+ 2-, PO 3 Ca 2+,,, or. 2. The compound according to claim 1, wherein: R7 is selected 2- from -PO 3 Na 2+, -PO3 2- K 2+, or -PO 2-3 Ca The compound according to claim 2, wherein R7 is -PO 2-3 Ca A pharmaceutical compositio on, comprising a compound according to any one of claims 1 to 3 in an amount effective to treat infection by a virus that is characterized by a virally-encoded aspartyl protease; and a pharmaceutically acceptable carrier,, adjuvant or vehicle. 9. A method for inhibiting aspartyl protease activity in a mammal, comprising the step of administering to said mammal a pharmaceut tical composition according to claim 4. Claim Construction The Board interprets claims by applying the broadest reasonable construction in the light of the specification in which it appears. 37 C.F.R (b); see, 77 Fed. Reg. 157 (August 14, 2012) at The terms recited in the claims of the 9899 Patent do not appear to be in dispute. Claims 1-3 are directed to a compound having a particularly recited 4

5 structure. Petitioner and Patent Owner appear to agree that the formula of claim 1 is a derivative of the HIV protease inhibitor known as VX-478. Claims 4-8 are directed to a pharmaceutical composition comprising an amount of the compound of claims 1-3 that is effective to treat infection by a virus that is characterized by a virally encoded aspartyl protease. The meaning of an amount effective to treat infection... does not appear to be in dispute. Claims 9-12 are directed to a method of inhibiting aspartyl protease activity in a mammal that includes the step of administering the pharmaceutical compositions of claim 4. THE PROPOSED GROUNDS OF UNPATENTABILITY Petitioner challenges the patentability of claims 1-12 of the 989 Patent on the following four grounds (Pet. 8-9): 1. Claims 1 and 2 under 35 U.S.C. 103(a) are unpatentable over Roy 1 in view of Grobelny 2 ; 2. Claims 3-12 under 35 U.S.C. 103(a) are unpatentable over Roy in view of Grobelny and Bighley; 3 1 Ex. 1021, US Patent 6,730,679 B1, issued May 4, 2004 to Roy et al. (hereinafter Roy or the 679 Patent ). 2 Ex. 1022, International Patent Publication WO 95/07269, published March 16, 1995, and naming Damian Grobelny as the sole inventor (hereinafter Grobelny or the 269 Publication ). 3 Ex. 1027, Bighley, et al., Salt Forms of Drugs and Absorption, Encyclopedia of Pharmaceutical Technology, Vol. 13, eds. Swarbrick, et al., Marcel Dekker Inc., New York, pp (1996) (hereinafter Bighley ). 5

6 3. Claims 1 and 2 under 35 U.S.C. 103(a) are unpatentable over Roy II 4 in view of Grobelny; and 4. Claims 3-12 under 35 U.S.C. 103(a) are unpatentable over Roy II in view of Grobelny and Bighley. Petitioner relies on the Declaration of Jed Fisher, 5 in support of the proposed grounds of unpatentability. Dr. Fisher is a faculty member of the Department of Chemistry and Biology at the University of Notre Dame with 35 years of medicinal chemistry experience, in particular, 7 years of experience researching and developing aspartyl protease inhibitors, including extensive research and development of HIV protease inhibitors. (Fisher Decl. 1, 2, and 7.) Dr. Fisher has several publications directed to HIV protease inhibitors and aspartyl protease inhibitors. (Fisher Decl. 4-5.) Patent Owner had not directed us to any reason to doubt Dr. Fisher s qualifications to testify as an expert in the field of HIV aspartyl protease inhibitors. We find Dr. Fisher to be qualified to testify concerning issues raised in this proceeding. Roy and Grobelny As set forth by Petitioner, Roy discloses that VX-478 was a known and effective HIV protease inhibitor with poor solubility. (Pet. 29; Roy, col. 1, ll ) Grobelny discloses a water-soluble disodium phosphate ester salt prodrug derived from a similar HIV aspartyl protease inhibitor with similar solubility 4 Ex. 1031, International Patent Publication WO 97/35587, published October 2, 1997, and naming Roy, et al. as inventors (hereinafter Roy II or the 587 Publication ). 5 Ex. 1002, Declaration of Jed Fisher, executed October 15, 2012 (hereinafter Fisher Declaration or Fisher Decl. ). 6

7 problems to that of VX-478. (Pet., p. 24 and 35; Grobelny, p. 86, l. 12.) Petitioner argues that one of ordinary skill in the art would have looked to the Grobelny publication to overcome VX-478 s solubility-related problems, described in Roy, in the same manner for improving solubility of another known HIV protease inhibitor, as described in the working examples of Grobelny (Pet ; Fisher Decl. 87.) In other words, the known solubility problem described in Roy would have been a sufficient reason for the skilled artisan to derivatize VX-478 with a phosphate ester salt in the manner taught by Grobelny. In determining whether a chemical compound would have been obvious, the correct inquiry is whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound [here VX-478] to make the claimed compound with a reasonable expectation of success. Otsuka Pharma. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1292 (Fed. Cir. 2012). Reason to modify VX-478 Patent Owner does not challenge that VX-478 was a known protease inhibitor and a reasonable subject for improved solubility. Rather, Patent Owner contends that Petitioner s characterization of the problem to be solved as merely increasing VX-478 s solubility ignores the complexity of the issues facing the skilled artisan in producing an effective HIV protease inhibitor pharmaceutical agent. (Prelim. Resp. 4.) A different characterization of the problem facing the 989 Patent s inventors is not persuasive. [T]he motivation in the prior art to combine the references does not have to be identical to that of the applicant to establish obviousness. In re Kemps, 97 F.3d 1427, 1430 (Fed. Cir. 1996). As long as some motivation or suggestion to combine the references is provided by the prior art taken as a whole, the law does not require that the references be combined for 7

8 the reasons contemplated by the inventor. In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007) ( [A]ny need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed. ). At the time of the invention, the evidence shows that a well-known problem for HIV protease inhibitors, including VX-478, was low solubility, which is said to be attributed to phenylalanine-like and/or proline-like portions common to HIV protease inhibitors. (See Roy, col. 2, ll ; Grobelny, p. 74, ll. 6-10; Fisher Decl. 44 and 47 (citing Ex at and Ex at 235).) Roy discloses that an objective at the time was lower quantities of drug administered to achieve the same therapeutic effect and fewer dosages required at less frequent intervals thereby improving patient compliance. (Roy, col. 2, ll ). Grobelny teaches that the inclusion of a solubilizing group Px as defined herein in a substance having low to very low water solubility results in enhancement of the water solubility of the substance, and that such substances exhibit superior bioavailability, including superior oral bioavailability, compared to compounds in accordance with the invention which do not include a solubilizing group Px. (Grobelny, p. 74, ll ; Pet. 23.) Further, Grobelny defines the expression solubilizing group Px as a group which may be used to derivatise a functional group so as to enhance solubility of the compound... in water or aqueous media. (Grobelny, p. 36, ll ). Grobelny discloses a number of exemplary solubilizing groups including phosphate esters or salts thereof, namely a salt of an alkali metal or ammonia, such as Na +, K + or NH 4 +. (Grobelny, p. 36, l. 22 to p. 37, l. 20.) 8

9 Grobelny s teaching of using a phosphate ester salt as a solubilizing agent was not specific to the HIV protease of its invention, but suggested the improvement to any low solubility compound. Accordingly, Petitioner has shown that the addition of a solubilizing group known to improve solubility of a low solubility compound is a sufficient reason to modify VX-478. See KSR, 550 U.S. at 417 (The question to be asked is whether the improvement is more than the predictable use of prior art elements according to their established functions. ). Patent Owner argues that, of the myriad means for addressing the solubility problems of VX-478, there was no roadmap to the solution to solubility chosen in the 989 Patent in the prior art (Prelim. Resp ). For example, Patent Owner argues that the skilled artisan would have considered improving the solubility of VX-478 by reformulating the known compound, the use of prodrug moieties other than the phosphate ester salt, or derivatizing a functional sites other than VX-478 s free hydroxyl. (Id.) Petitioner points out that Patent Owner relies on similar arguments made during prosecution of the 989 Patent based on a disclosure in Banker 6 of a number of prodrug moieties that could have been used to improve solubility. (Pet ) Petitioner also points out that, the Declaration of Pravin Chaturvedi 7 supported Patent Owner s position during prosecution that Banker failed to direct the skilled artisan to phosphate ester salts over any other potential prodrug moiety. (Pet ; Ex. 1029, p. 287, 11. See also Ex. 1029, pp and 344; Prelim. Resp. 39.) 6 Ex. 1030, Banker et al., Modern Pharmaceutics, Marcel Dekker, pp (1996) (hereinafter Banker ). 7 Ex. 1029, p , Declaration of Pravin Chaturvedi, executed December 8, 2000 (hereinafter Chaturvedi Decl. or Chaturvedi Decl. ). 9

10 Patent Owner is correct that Banker and Grobelny disclose a number of prodrug moieties in addition to phosphate ester salts. (Grobelny, p. 36, l. 22 to p. 37, l. 20; Banker, p. 628, Table 5). However, as pointed out by Petitioner, Grobelny describes a process specific to forming a phosphate ester salt in Examples 4, 5, and 8 by derivatizing a free hydroxyl positioned similarly to that of the free hydroxyl of VX-478. (Grobelny, p. 86, l. 8 to 15, see p. 76, ll. 4-7; Pet ; Fisher Dec. 65.) Thus, it appears that Grobelny provides an exemplary roadmap for using a phosphate ester salt derivative at the free hydroxyl of VX-478 for solving the solubility problem of VX-478 that was missing in the teaching of Banker during prosecution of the 989 Patent. Reasonable Expectation of Success Patent Owner further contends that there was no reasonable expectation of success that a phosphate ester salt derivative of VX-478 would have been successful either (a) in solving the solubility problem of VX-478 or (b) as a bioavailable alternative to VX-478. As pointed out by Petitioner, Grobelny discloses a prodrug similar in structure to the compound claimed in the 989 Patent, namely a disodium phosphate ester salt of t-butyl 3-isopropyl-3-[(2S,3S)-2-hydroxy-3-(N-quinaldoyl- L-asparaginyl)amino-4-phenylbutyl carbazate purported to have the following structure prior to the conversion to a salt (Pet., p. 24 and 35; Grobelny, p. 86, ll. 11). 10

11 The above is a chemical structure of Example 5 of Grobelny purported to be t-butyl 3-isopropy yl-3-[(2s,3s)-2-hydroxy-3-(n-quinaldoyl-l-asparaginyl)amino-4- s in structure between VX-478 and phenylbutyl carbazate. Petitioner further describes the similarities the exemplary compound of Grobelny, namely the presence of a free hydroxyl group between a phenylalan nine mimetic and an N-alkyl group, as exemplified in the comparative structures from the Petition reproduced below. (Pet. 35; Fisher Decl. 65.) 11

12 This figure is purported to be a comparison of the structures of VX-478 and the structure of Example 4 of Grobelny. (Pet. 35; Fisher Decl. 65.) The figure depicts similar structures said to be a hydroxyl group positioned between a phenylalanine mimetic and an N-alkyl circled with the remaining portions of the structures in phantom lines. Petitioner further tracks the process described in Examples 4, 5, and 8 of Grobelny against that described in the 989 Patent, suggesting that the only distinction in the process is that the 989 Patent describes converting to the corresponding sodium salt under specific conditions not disclosed in Grobelny. (Pet. 33; Fisher Decl. 88; see 989 Patent col. 57, l. 1 to col. 59, l. 6; Grobelny, p. 86, l. 8 to p. 87, l. 19 and p. 89, ll ) Given the similarities between structures of the HIV protease inhibitor of Grobelny and VX-478 and disclosure of a precise method for modifying the similar structure, Petitioner argues that there was a reasonable likelihood that one of ordinary skill in the art would have been successful in preparing a derivative of VX-478 having the claimed structure with similar improvement in solubility and bioavailability as found for the HIV protease inhibitor of Grobelny, using the teachings of Grobelny. (Pet ) [I]t is sufficient to show that the claimed and prior art compounds possess a sufficiently close relationship... to create an expectation, in light of the totality of the prior art, that the new compound will have similar properties to the old. Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301 (Fed. Cir. 2007) (quoting In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990)); see also In re Wilder, 563 F.2d 457, 460 (CCPA 1977) ( [O]ne who claims a compound, per se, which is structurally similar to a prior art compound must rebut the presumed expectation that the structurally similar compounds have similar properties. ). We 12

13 agree that the similar structure and disclosure of similar solubility problems associated with that structure would have provided a reasonable expectation of success in improving solubility using the methods taught by Grobelny. Patent Owner argues that Grobelny s examples do not show an improvement in solubility because there is no comparison between the measured solubility of the derived HIV protease inhibitor and the HIV protease inhibitor from which it was derived. (Prelim. Resp ) However, Grobelny states expressly that the inclusion of a solubilizing group Px as defined herein in a substance having low to very low water solubility results in enhancement of the water solubility of the substance. (Grobelny, p. 74, ll (emphasis added).) Patent Owner has provided no persuasive evidence to challenge the veracity of this statement in the prior art. Dr. Fisher testifies for Petitioner that the water solubility of the phosphate ester salt prodrug measured in Example 8 of Grobelny, namely 30 mg/ml solution, is orders of magnitude greater than the typical solubility for HIV protease inhibitors. (Ex. 1002, 66.) We credit Dr. Fisher with having knowledge of the solubility of HIV protease inhibitors generally and find his testimony consistent with the teaching of Roy that VX-478 has a solubility of only mg/ml. (Roy, col. 2, ll ) Although Patent Owner is correct that Dr. Fisher s testimony does not prove that, in fact, there was improvement in water solubility of the compound of Example 8 (Prelim. Resp. 30), Dr. Fisher s testimony evinces that Grobelny s express statement of improvement is reasonable. Thus, it is likely that one skilled in the art would have had a reasonable expectation of success in improving solubility for a phosphate ester prodrug of VX-478 at the time the invention was made, and merely had to verify that expectation. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007) 13

14 (simply because the properties of a compound must be verified through testing does not mean that the compound lack an expection for success since the expectation of success need only be reasonable, not absolute ). Accordingly, we are not persuaded that the skilled artisan would not have expected some degree of improvement in solubility with the free hydroxyl group of VX-478 derivatized with a phosphate ester salt, as exemplified in Grobelny. Patent Owner further argues that structural similarity is not evidence of similar properties. (Prelim. Resp ) To refute Petitioner s evidence of other non-protease inhibitor drugs that were improved by a phosphate ester prodrug moiety (see e.g., Pet. 17), 8 Patent Owner puts forth evidence of derivatives of other HIV protease inhibitors, 9 and derivatives of other non-protease inhibitor drugs with secondary alcohols, 10 which demonstrated no or a slow rate of bioavailability even with improved solubility. (Id. at ) Patent Owner also showed structural 8 See Ex. 1018, Physicians Desk Reference, Medical Economics Data Production Co., Montvale, NJ, pp (1995). 9 See Ex. 2008, DeGoey, et al. Water-Soluble Prodrugs of the Human Immunodeficiency Virus Protease Inhibitors Lopinavir and Rotinavir, J. Med. Chem., Vol. 52, pp (2009) (hereinafter DeGoey ). 10 Ex. 2006, Nicolaou et al., Phosphate Prodrugs for Amines Utilizing a Fast Intramolecular Hydroxy Amide Lactonization, J. Org. Chem., Vol. 61, pp (1996) (hereinafter Nicolaou ); Ex. 2007, Safadi, et al., Phosphoryloxymethyl Carbamates and Crabonates Novel Water-Soluble Prodrugs for Amines and Hindered Alcohols, Pharma. Res., Vol. 10 (pp ) (1993) (hereinafter Safadi ). 14

15 isomers having different rates of hydrolysis by alkaline phosphatase. 11 In the words of Patent Owner, [s]ome worked. Some did not. (Id. at 33.) Patent Owner further argues that solubility is not an indication of bioavailability or usefulness in reducing pill burden, and accordingly, the skilled artisan would not have had expected success in producing a useful prodrug. (Id. at 27 and 38-42). With respect to bioavailability and reduction in pill burden, we note that claims 1 and 2 are directed to a compound of a particular structure. The claims do not require any degree of bioavailability or therapeutic effect. 12 Accordingly, for obvious analysis, there need only be an expectation that the purpose for the proposed modification (i.e., improvement in solubility) be expected to succeed. Otsuka, 678 F.3d at Moreover, the examples provided by Patent Owner of poor bioavailability, many of which were tested after the invention date and have structures lacking the similar characteristics of VX-478 and Grobelny s HIV protease inhibitor, are not sufficient evidence that the skilled artisan at the time would not have had a reasonable expectation of successful bioavailability. To the extent that Patent 11 See Ex. 2005, Kearney, et al., The in Vitro Enzymatic Labilities of Chemically Distinct Phosphomonester Prodrugs, Pharma. Res., Vol. 9, No. 4, pp (April 1992) (hereinafter Kearney ). 12 We note that claims 4-12 are directed to a pharmaceutical composition... in an amount effective to treat infection by a virus... that may be interpreted as requiring some degree of bioavailability in the VX-478 derivative claimed. However, Patent Owner s arguments are not directed to claims In fact, with respect to claims 4-12, Patent Owner merely states that [f]or the same reasons discuss above..., the 679 patent and the 269 publication do not render claims 4-12 obvious. Nothing in Bighley addresses or cures the deficiencies of the 679 patent and 269 publication. (PO Prelim. Resp. 43.) 15

16 Owner suggests Petitioner s evidence represents outlying examples of successful phosphate ester derivatives, so too might Patent Owner s examples represent unsuccessful outlying examples. When we evaluate the evidence before us as a whole, we conclude that one skilled in the art would have reasonably expected increased bioavailability. Petitioner has produced sufficient evidence that prodrugs and the process by which naturally present alkaline phosphatase converts prodrugs in vivo were well known at the time of the invention. (Pet (citing Exs and 1020); Fisher Decl. 55). Further, Grobelny exhibits that such conversion took place in dog studies. (Grobelny, p. 90, ll ) Thus, we are persuaded that the skilled artisan would have also had an expectation of success in using a phosphate ester salt prodrug derived from VX-478 as a useful prodrug, to the same extent that the structure of Grobelny was a useful prodrug, because of the similarity in structure. Aventis, 499 F.3d at 1301; Dillon, 919 F.2d at 692; Wilder, 563 F.2d at 460. As discussed above, the expectation of success need only be reasonable, not absolute. Pfizer, 480 F.3d at Petitioner further argues that Patent Owner would unlikely be successful in proving secondary considerations because (a) Grobelny would render any success achieved to be expected, (b) Grobelny fully addresses any long-felt need in the art, and (c) Patent Owner s grant of a patent suggests that any evidence of commercial success would be outweighed by a lack of competition in the market. (Pet ) Patent Owner argues that it will be able to show evidence of secondary considerations of non-obviousness. (Prelim. Resp ) However, no such persuasive evidence has yet been presented. We note that Roy is prior art under 35 U.S.C. 102(e), in that it is a patent granted on an application filed March 20, 1997 (with a priority claimed to March 16

17 22, 1996), that is before the filing date of the 989 patent, December 24, Patent Owner does not argue that Roy is not prior art or the ability to demonstrate an invention date prior to the appropriate filing date of Roy. We are persuaded by the analysis set forth in the Petition and accompanying Fisher Declaration that there is a reasonable likelihood that Petitioner will prevail on its assertion that claims 1 and 2 are obvious over Roy and Grobelny under 35 U.S.C. 103(a). Roy, Grobelny and Bighley Claim 3 Petitioner argues that the decision tree and disclosure of the four most common salts of Bighley evinces that calcium salts were known alternative salts to the sodium, potassium, and magnesium salts disclosed by Grobelny (Pet ) Patent Owner does not dispute Petitioner s position and, instead, relies on arguments presented with respect to claims 1 and 2. (Prelim. Resp ) We are persuaded by the analysis set forth in the Petition and accompanying Fisher Declaration. (Fischer Decl at ) Accordingly, there is a reasonable likelihood that Petitioner would prevail on its assertion that claim 3 is obvious under 35 U.S.C. 103(a) over Roy in view of Grobelny and Bighley. Claims 4-12 Regarding claims 4-12, Petitioner s position is that the claims recite elements that would naturally follow using an HIV protease as indicated by the teachings of Roy and Grobelny. (Pet ) Indeed, Roy discloses that VX-478 may be provided in an oral dosage form for the treatment or prophylaxis of HIV infections. (Roy, col. 6, ll and 59-17

18 65.) Roy discloses that a pharmaceutically effective amount of VX-478 is a dose of about 8 to 50 mg/kg of body weight per day and may be provided in one to four subdoses of 25 to 500mg per unit dosage. (Roy, col. 6, ll ) Formulations thereof may include other therapeutic agents, such as ritonavir and other HIV protease inhibitors. (Roy col. 6, l. 66-col. 7, l. 11.) Patent Owner does not dispute Petitioner s position and, instead, relies on arguments presented with respect to claims 1 and 2. (Prelim. Resp. 43.) We are persuaded by the analysis set forth in the Petition and accompanying Fisher Declaration. (Fischer Decl at ) Accordingly, there is a reasonable likelihood that Petitioner would prevail on its assertion that claims 4-12 are obvious under 35 U.S.C. 103(a) over Roy in view of Grobelny and Bighley. Identical Grounds based on Roy II as an alternative to Roy Petitioner asserts that the disclosure in Roy II is almost identical to that of Roy discussed above, and there is no distinction in Petitioner s arguments with respect to Roy II over that of Roy (Pet. 54.) Patent Owner agrees that the disclosures are substantially identical, and there is no distinction in Patent Owner s arguments with respect to Roy II over that of Roy (Prelim. Resp. 44). Accordingly, for the same reasons discussed above with respect to Roy, there is a reasonable likelihood that Petitioner would prevail on its assertion that claims 1 and 2 are obvious under 35 U.S.C. 103(a) over Roy II in view of Grobelny. Likewise, there is a reasonable likelihood that Petitioner would prevail on its assertion that claims 3-12 are obvious under 35 U.S.C. 103(a) over Roy II in view of Grobelny and Bighley. We note that Roy II is prior art under 35 U.S.C. 102(a), in that it was published on October 2, 1997, which is less than one year before the filing date of 18

19 the 989 patent, December 24, Patent Owner does not argue that Roy II is not prior art or the ability to demonstrate an invention date prior to the publication date of Roy II. We determine that it is not necessary to proceed on grounds based on both Roy and Roy II. The substantive arguments are cumulative as the disclosures of Roy and Roy II are identical. Moreover, Roy and Roy II assert the same priority. Thus, should Patent Owner opt to establish an earlier invention date so as to remove Roy as 102(e) prior art, the earlier invention date would likewise remove Roy II as 102(a) prior art. Proceeding based on Roy II would thus be redundant. See Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co., CBM (Paper No. 7), at *2 (PTAB Oct. 25, 2012) (not proceeding on redundant grounds in absence of meaningful distinction); see also 37 C.F.R. 42.1(b) ( This part [i.e., Part 42 of Title 37, Code of Federal Regulations] shall be construed to secure the just, speedy, and inexpensive resolution of every proceeding. ); 37 C.F.R (a) ( When instituting inter partes review, the Board may authorize the review to proceed on all or some of the challenged claims and on all or some of the grounds of unpatentability asserted for each claim. ). CONCLUSION Petitioner has demonstrated a reasonable likelihood of prevailing on its challenge of claims 1 and 2 of the 989 Patent under 35 U.S.C. 103 as unpatentable over Roy in view of Grobelny. Petitioner has demonstrated a reasonable likelihood of prevailing on its challenge of claims 3-12 of the 989 Patent under 35 U.S.C. 103 as unpatentable over Roy in view of Grobelny and Bighley. 19

20 It is Order ORDERED that the Petition is granted as to claims 1 and 2 of the 989 Patent on the proposed ground of unpatenability under 35 U.S.C. 103(a) over Roy in view of Grobelny; FURTHER ORDERED that the Petition is granted as to claims 3-12 of the 989 Patent on the alleged ground of unpatentability under 35 U.S.C. 103(a) over Roy in view of Grobelny and Bighley; FURTHER ORDERED that the Petition is denied as to claims 1 and 2 of the 989 Patent on the proposed ground of unpatentability under 35 U.S.C. 103(a) based on Roy II in view Grobelny; FURTHER ORDERED that the Petition is denied as to claims 3-12 of the 989 Patent on the alleged ground of unpatentability under 35 U.S.C. 103(a) over Roy II in view of Grobelny and Bighley; FURTHER ORDERED that pursuant to 35 U.S.C. 314(a), a trial for inter partes review of the 989 patent is hereby instituted, commencing on the entry date of this Order, and pursuant to 35 U.S.C. 314(c) and 37 C.F.R. 42.4, notice is hereby given of the institution of trial; FURTHER ORDERED that the trial is limited to the above-granted proposed grounds of unpatentability directed to claims 1-12, and that no other ground for any claim is authorized for trial; and FURTHER ORDERED that an initial conference call with the Board is scheduled for 2:00 pm EDT on April 4, 2013; the parties are directed to the Office Trial Practice Guide, 77 Fed. Reg , (Aug. 14, 2012) for guidance in preparing for the initial conference call, and should come prepared to 20

21 discuss any proposed changes to the Scheduling Order entered herewith and any motions the parties anticipate filing during the trial. For PETITIONER: Brenton R. Babcock KNOBBE, MARTENS, OLSON & BEAR, LLP For PATENT OWNER James F. Haley, Jr. Karen Mangasarian ROPES & GRAY 21