Trials@uspto.gov
`571-272-7822
`
`
` Paper 8
`
`Entered: April 29, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`____________
`
`Case IPR2016-00084
`Patent 5,665,772
`____________
`
`
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`CRUMBLEY, Administrative Patent Judge.
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`35 U.S.C. § 314(a) and 37 C.F.R. § 42.108
`
`
`
`
`
`
`
`571-272-7822
`
`
` Paper 8
`
`Entered: April 29, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`____________
`
`Case IPR2016-00084
`Patent 5,665,772
`____________
`
`
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`CRUMBLEY, Administrative Patent Judge.
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`35 U.S.C. § 314(a) and 37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`I. INTRODUCTION
`
`Par Pharmaceutical Inc. (“Par”) filed a Petition requesting an inter
`partes review of claims 1–3 and 8–10 of U.S. Patent No. 5,665,772 (Ex.
`1001, “the ’772 patent”). Paper 2 (“Pet.”). Novartis AG, the assignee of the
`’772 patent, filed a Preliminary Response to the Petition. Paper 7 (“Prelim.
`Resp.”).
`Pursuant to 35 U.S.C. § 314(a), an inter partes review may not be
`instituted unless the information presented in the Petition and any
`Preliminary Response shows “there is a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in
`the petition.” Taking into account the information presented, we conclude
`that the record establishes that there is a reasonable likelihood that Par will
`prevail with respect to at least one of the challenged claims of the ’772
`patent. Accordingly, we institute trial as set forth below.
`
`A. Related Matters
`
`We are informed that the ’772 patent has been asserted in several
`actions captioned Novartis Pharm. Corp. et al. v. Breckenridge Pharm., Inc.,
`No. 14-1043-RGA (D. Del.); Novartis Pharm. Corp. et al. v. Roxane Labs.,
`Inc., No. 14-1196-RGA (D. Del.); Novartis Pharm. Corp. et al. v. Par
`Pharm., Inc., No. 14-1289-RGA (D. Del.); Novartis Pharm. Corp. et al. v.
`Par Pharm., Inc., No. 14-1494-RGA (D. Del.); Novartis Pharm. Corp. et al.
`v. Roxane Labs., Inc., No. 14-1508-RGA (D. Del.); Novartis Pharm. Corp.
`et al. v. Par Pharm., Inc., No. 15-78-RGA (D. Del.); and Novartis Pharm.
`Corp. et al. v. Roxane Labs., Inc., No. 15-128-RGA (D. Del.). Pet. 3; Paper
`
`
`
`2
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`5, 1. Related U.S. Patent No. 6,455,518 has been challenged in IPR2016-
`00078, currently pending before the Board.
`
`B. The ’772 Patent
`
`The ’772 patent, titled “O-alkylated Rapamycin Derivatives and Their
`Use, Particularly as Immunosuppressants,” issued September 9, 1997, from
`U.S. Patent Application No. 08/416,673, filed on September 24, 1993.
`Ex. 1001, (54), (45), (21), (22). The patent is directed to derivatives of
`rapamycin, which are said to have pharmaceutical utility, particularly as
`immunosuppressants. Ex. 1001, Abstract.
`Rapamycin is a known immunosuppressant having the following
`chemical structure:
`
`
`Id. at 1:15. The ’772 patent discloses various derivatives of rapamycin, in
`particular alkylated derivatives having substitutions at the 9, 26, 28, 39, or
`40 carbon. Id. at 1:50–2:19 (Formula I). Of these derivatives, the “preferred
`novel compounds” are the 40-O-substituted rapamycins. Id. at 2:55–56.
`
`According to the ’772 patent, the disclosed rapamycin derivatives are
`particularly useful for treatment and prevention of a range of conditions,
`3
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`including: organ or tissue transplant rejection; autoimmune disease and
`inflammatory conditions; asthma; multi-drug resistance; tumors; fungal
`infections; inflammation; infection; and overdoses of other
`immunosuppressants. Id. at 3:22–4:10. The preferred 40-O-substituted
`derivatives are said to be highly immunosuppressive and are particularly
`useful in treating transplant rejection or autoimmune disease. Id. at 4:21–25.
`
`C. Illustrative Claims
`
`Of the challenged claims, claim 1 is independent, and is reproduced
`
`below:
`
`1. A compound of the formula:
`
`
`wherein R1 is hydroxy(C1–6)alkyl or
`hydroxy(C1–3)alkoxy(C1–3)alkyl.
`Ex. 1001, 21:13–22:2.1
`
`
`
`
`1 The chemical formula of claim 1 was corrected in a Certificate of
`Correction dated February 9, 2016.
`
`4
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`Claims 2 and 3 depend from claim 1 and further restrict the
`substitutions that may be made at R1. Id. at 22:4–7. Claim 10 depends from
`claim 1 and recites a particular species within the genera of claims 1–3:
`namely, 40-O-(2-hydroxyethyl)-rapamycin (“everolimus”2). Id. at 22:28–
`29.3 Finally, claims 8 and 9 recite methods of using the compounds of claim
`1, to induce an immunosuppressant effect or to prevent allograft rejection,
`respectively. Id. at 22:19–27.
`
`D. Asserted Grounds of Unpatentability
`
`Par challenges claims 1–3 and 8–10 of the ’772 patent on the
`
`following grounds of unpatentability:
`
`
`2 Novartis refers to 40-O-(2-hydroxyethyl)-rapamycin as “everolimus,”
`terminology we adopt for the purposes of this Decision.
`3 Claim 10, as issued, recited “40-O-(3-hydroxyethyl)-rapamycin.” In a
`Certificate of Correction dated June 30, 1998, this was corrected to “40-O-
`(2-hydroxyethyl)-rapamycin.”
`
`5
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`References
`Morris,5 Van Duyne,6 Rossmann,7
`Yalkowski,8 and Lemke9
`Morris, Van Duyne, Rossmann,
`Yalkowski, Lemke, and Hughes10
`Morris, Van Duyne, Yalkowski, Lemke,
`and “routine use of computer-aided
`design”
`Morris, Van Duyne, Yalkowski, Lemke,
`“routine use of computer-aided design,”
`and Hughes
`
`Basis4 Challenged Claim(s)
`§ 103(a) 1–3, 10
`
`§ 103(a) 8, 9
`
`§ 103(a) 1–3, 10
`
`§ 103(a) 8, 9
`
`
`4 The relevant sections of the Leahy-Smith America Invents Act (“AIA”),
`Pub. L. No. 112–29, took effect on March 16, 2013. Because the application
`from which the ’264 patent issued was filed before that date, our citations to
`Title 35 are to its pre-AIA version.
`5 Randall Ellis Morris, Rapamycins: Antifungal, Antitumor,
`Antiproliferative, and Immunosuppressive Macrolides, 6 TRANSPLANTATION
`REVIEWS 39-87 (1992) (Ex. 1005).
`6 Gregory D. Van Duyne et al., Atomic Structure of the Rapamycin Human
`Immunophilin FKBP-12 Complex, 113 J. AM. CHEM. SOC’Y 7433–35 (1991)
`(Ex. 1006).
`7 Michael G. Rossmann et al., Three-Dimensional Coordinates from
`Stereodiagrams of Molecular Structures, B36 ACTA CRYST. 819–823 (1980)
`(Ex. 1024).
`8 Samuel H. Yalkowsky, Estimation of Entropies of Fusion of Organic
`Compounds, 18 INDUS. ENG’G CHEM. FUNDAM. 108–11 (1979) (Ex. 1007).
`9 Thomas L. Lemke, Chapter 16: Predicting Water Solubility, REVIEW OF
`ORGANIC FUNCTIONAL GROUPS 113–21 (2d ed. 1988) (Ex. 1008).
`10 U.S. Patent 5,233,036 (Aug. 3, 1993) (Ex. 1009).
`6
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`Par asserts that Morris is prior art to the ’772 patent under 35 U.S.C.
`
`§ 102(a); Rossmann, Van Duyne, Yalkowski, and Lemke are prior art under
`35 U.S.C. § 102(b); and Hughes is prior art under 35 U.S.C. § 102(e). Pet.
`26, 27, 32, 33, 34. Novartis does not, at this stage of the proceeding,
`challenge the prior art status of any reference.
`
`II. ANALYSIS
`
`A. Claim Construction
`
`Neither party asks that we construe any term used in the challenged
`claims. Upon review, we agree that no terms require an express construction
`at this stage of the proceeding.
`
`B. Obviousness Over Morris, Van Duyne, Rossmann,
`Yalkowski, and Lemke
`Par contends that claims 1–3 and 10 are unpatentable under 35 U.S.C.
`
`§ 103(a), as their subject matter would have been obvious over the combined
`disclosures of Morris, Van Duyne, Rossmann, Yalkowski, and Lemke. Pet.
`40–48. Par explains how the combined references teach the subject matter
`of each challenged claim and asserts that a person of ordinary skill in the art
`would have had reason to combine or modify the references. Id. Par also
`relies upon the Declaration of Dr. William Jorgensen (Ex. 1003) to support
`its positions.
`Morris is a review of the research into rapamycin, “written relatively
`early in the research life of [rapamycin].” Ex. 1005, 41. Rapamycin is said
`to be “particularly intriguing because it inhibits the activation of immune
`cells by unique, relatively selective, and extremely potent and highly
`effective mechanisms.” Id. at 39. Morris reports that while water soluble
`7
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`prodrugs of rapamycin have been synthesized, rapamycin itself is only
`minimally soluble in water, at 20 µg/mL. Id. at 46. Furthermore, Morris
`states that the toxicity of rapamycin is “not known,” but that mice and rats
`appear to be very resistant to acute toxic effects of the drug. Id. at 49. Large
`animals were found to be more susceptible to toxic effects. Id. at 50–51.
`Nevertheless, Morris concludes that rapamycin and other new
`immunosuppressants “enable combination immunosuppressive therapy to
`reach new levels of sophistication” and “offer the hope that rejection can be
`prevented and treated more effectively and safely than ever before.” Id. at
`82.
`
`Van Duyne is a study of the atomic structure of the complex of
`rapamycin and FKBP-12, the immunophilin to which rapamycin binds. Ex.
`1006, 7433. Van Duyne contains a stereodiagram of the alpha-carbon
`structure of the rapamycin/FKBP-12 complex, and discloses that rapamycin
`binds in a cavity in the FKBP-12 protein. Id. at 7433–34. The interface is
`said to involve atoms from rapamycin’s pyranose ring through the C28
`hydroxyl, but also involves two additional hydrogen bonds, one being at the
`C40 hydroxyl. Id. at 7434. Van Duyne states that coordinates of the bound
`rapamycin complex are available from its authors, and will be deposited in
`the Brookhaven Protein Databank. Id.
`Rossmann discloses a method of deriving three-dimensional
`coordinates from stereodiagrams of molecular architecture. Ex. 1024, 819.
`Rossmann notes that many publications provide stereodiagrams of proteins
`and nucleic acids, but do not provide coordinates for the structure which
`would permit quantitative use of the published structural data. Id.
`
`
`
`8
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`Yalkowski discusses the estimation of the entropy of fusion for drugs
`and molecules of intermediate size. Ex. 1007, 108. Longer chains are said
`to contribute to internal entropy by 2.5 (n – 5) eu, where n is the number of
`atoms in the chain. Id. at 111. Dr. Jorgensen testifies that this means that
`“each added rotatable bond is worth approximately 2.5 eu (cal/mol-K),
`which translates to a favorable contribution of (298 x 2.5 x 0.001) = 0.745
`kcal/mol to the free energy of fusion. Based on fundamental
`thermodynamics of equilibrium (ΔG = -2.3RT log K), each 1.3 kcal/mol
`provides a factor of 10 change in an equilibrium process such as solubility.”
`Ex. 1003 ¶ 79.
`Lemke provides a summary of the solubilizing potential of various
`functional groups in Table 16–1. Ex. 1008, 115–16. For example, in a
`polyfunctional molecule, an alcohol group is said to have the potential to
`solubilize 3–4 carbons, while an amine group may solubilize 3 carbons. Id.
`
`1. Par’s Lead Compound Analysis
`To support its contention of obviousness, Par sets forth a “lead
`compound analysis” explaining how a person of ordinary skill in the art
`would have modified rapamycin to arrive at everolimus, the compound
`recited in claim 10 of the ’772 patent. Pet. 40. A lead compound analysis
`follows a two-part inquiry. First, we “determine[] whether a chemist of
`ordinary skill would have selected the asserted prior art compounds as lead
`compounds, or starting points, for further development efforts.” Otsuka
`Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012). A
`compound may be considered a candidate “lead compound” if it is “most
`promising to modify in order to improve upon its . . . activity,” or “a natural
`9
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`choice for further development efforts.” Takeda Chem. Indus., Ltd. v.
`Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007); Altana
`Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009).
`The question of whether a person of ordinary skill in the art would have
`selected a compound as a lead compound is “guided by evidence of the
`compound’s pertinent properties.” Otsuka, 678 F.3d at 1292.
`Once it is determined that a person of ordinary skill in the art would
`have selected a particular lead compound, the second part of the analysis
`asks whether the artisan would have had reason to modify the lead
`compound to make the claimed compound, with a reasonable expectation of
`success. Id.
`Par’s proposed lead compound analysis may be summarized as
`follows. First, Par contends that a person of ordinary skill in the art would
`have selected rapamycin as a lead compound for developing improved
`immunosuppressants. Pet. 26. As support, Par cites Morris’ disclosure of
`rapamycin’s “potent immunosuppressant activities,” as well as its
`description of rapamycin as “particularly intriguing.” Id. (citing Ex. 1005,
`39–42). Dr. Jorgensen testifies in support of this contention, also citing Van
`Duyne’s disclosure of the structure of rapamycin bound to FKBP-12,
`contending that this would have given the person of ordinary skill in the art
`further reason to select rapamycin as lead compound. Ex. 1003 ¶¶ 132–137.
`Par notes, however, that rapamycin was known to have low solubility,
`and that this would have been understood to limit the bioavailability of the
`drug. Pet. 41 (citing Ex. 1005, 46; Ex. 1003 ¶¶ 138–140). Par contends that
`
`
`
`10
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`a person of ordinary skill in the art would have had reason to modify
`rapamycin’s solubility to increase its bioavailability. Id. at 41–42.
`Having selected rapamycin as a lead compound that might benefit
`from modification, Par alleges a person of ordinary skill in the art would
`have turned to Van Duyne’s disclosure of the structure of rapamycin bound
`to the FKBP-12 protein, to understand the interaction of the drug with its
`known biological targets. Id. at 42. Dr. Jorgensen testifies that the skilled
`artisan would have first looked to rapamycin’s hydroxyl groups located at
`C10, C28, and C40 as potential sites for substitution. Ex. 1003 ¶ 142. Van
`Duyne allegedly discloses that rapamycin’s C40 carbon is located on the
`periphery of the binding with FKBP-12, whereas C10 and C28 are part of
`the binding domain. Id.; Ex. 1006, 7434.
`Par contends the skilled artisan would have used the method of
`Rossmann to convert Van Duyne’s stereograms into the alpha-carbon
`structural coordinates of the rapamycin/FKBP-12 complex, which would
`have further confirmed the potential of C40 as a site for substitution. Pet.
`43–44. Dr. Jorgensen goes further, stating that the coordinates of the full
`structure of the rapamycin/FKBP-12 complex could have been obtained by
`contacting the authors of Van Duyne, and a person of ordinary skill in the art
`could have constructed a full three-dimensional model of the complex using
`known computer models. Ex. 1003 ¶¶ 113–14. From these models, Dr.
`Jorgensen concludes, the skilled artisan would have confirmed the suitability
`of C40 as a potential site for substitution. Id. ¶¶ 115–20.
`Finally, Par argues that a person of ordinary skill in the art would have
`looked to Yalkowski and Lemke to determine which substitutions to make at
`
`
`
`11
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`C40, and would have ultimately decided to attempt introduction of a flexible
`side chain containing an alcohol, amine, or carboxylic acid group. Pet. 44–
`47. Dr. Jorgensen testifies that small substituents would have been
`attempted first, therefore the skilled artisan would have selected three initial
`candidates: the 2-hydroxyethoxy group (OCH2CH2OH), the 2-aminoethoxy
`group (OCH2CH2NH2), and the carboxymethoxy group (OCH2COOH). Ex.
`1003 ¶¶ 150–53. Par notes that rapamycin modified to include a 2-
`hydroxyethoxy group at C40 is the particular derivative claimed in claim 10,
`40-O-(2-hydroxyethyl)-rapamycin (everolimus). Pet. 48. Because this
`compound falls within the scope of claims 1–3 as well, Par asserts that this
`lead compound analysis demonstrates the obviousness of claims 1–3 and 10.
`Id.
`
`2. Reliance on Rossmann as Prior Art
`Novartis asks that we deny institution of trial on this ground, because
`it relies on prior art that is not a patent or printed publication and thus is
`outside the scope of an inter partes review under 35 U.S.C. § 311(b).
`Prelim. Resp. 3. In particular, Novartis directs our attention to Par’s
`allegation that Rossmann discloses “software” that would have permitted a
`person of ordinary skill in the art to extract three-dimensional coordinates
`from Van Duyne’s two-dimensional stereogram. Id. Novartis argues that
`the alleged software of Rossmann has not been provided in the record as a
`printed publication, and, therefore, cannot be relied upon. Id. at 4.
`Upon review, we do not understand Par’s reliance on Rossmann to be
`improper for an inter partes review. Rossmann discloses a mathematical
`method for converting stereodiagrams into three-dimensional coordinates.
`12
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`Ex. 1024, 819. Par asserts that a person of ordinary skill in the art would
`have used this method as part of its lead compound analysis. To the extent
`that computer software was available at the time of the invention to aid in
`implementing Rossmann’s method, we consider this to be part of the
`background level of knowledge in the field, which can be relied upon given
`a sufficient evidentiary basis. We do not consider 35 U.S.C. § 311(b)’s
`restriction on the scope of prior art in inter partes reviews to restrict
`evidence of the background level of skill to only patents and printed
`publications.
`
`3. Selection of Lead Compound
`Novartis also challenges Par’s identification of rapamycin as a lead
`compound meriting further study and modification. Prelim. Resp. 5–12.
`Novartis cites Morris’ disclosure that in 1992, it was “relatively early in the
`research life” of rapamycin, and that little was known about the compound.
`Id. at 8 (citing Ex. 1005, 41). In addition, Novartis notes that there is no
`evidence of the use of rapamycin in humans at the time, and that the known
`toxicity of the compound would have led away from testing it in humans.
`Id. at 7. According to Novartis, there were a number of other
`immunosuppressants known at the time that would have been considered
`more promising for further investigation, and whose biological targets and
`mechanism of action were better understood. Id. at 6.
`Novartis appears to suggest that, in order for a compound to be
`selected as a lead compound, the law requires that it be considered the “most
`promising to modify.” Id. at 5 (quoting Otsuka, 678 F.3d at 1291) (emphasis
`Novartis’). Because there were other, more promising, candidates known at
`13
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`the time other than rapamycin, Novartis contends that Par has failed to
`demonstrate that rapamycin was the most promising and would have been
`selected as a lead compound. Id. at 6–7.
`We do not understand the lead compound analysis framework to be as
`rigid or absolute as Novartis contends. The Otsuka court did not state that
`only the “most promising” candidate compound may be considered a lead
`compound for further analysis. In fact, this interpretation is contradicted
`elsewhere in the decision. See Otsuka, 678 F.3d 1293 (“[T]he [District]
`court did not require, as the Defendants allege, that only ‘the most obvious
`choice’ could serve as the lead.”).
`At this stage of the proceeding, Par has set forth evidence that
`rapamycin was a promising immunosuppressant at the time of the invention,
`and Novartis has provided evidence that rapamycin had known drawbacks
`and that other immunosuppressants were also promising. This is not fatal to
`Par’s case at this time; rather, a genuine issue of material fact exists as to
`whether rapamycin would have been selected as a lead compound.
`
`4. Novartis’ Remaining Arguments
`Novartis raises numerous other arguments, indicating potential flaws
`in Par’s lead compound analysis or disputing Par’s interpretation of the
`disclosures of the cited references. For example, Norvartis notes Van
`Duyne’s disclosure that rapamycin’s C40 hydroxyl group is involved in
`hydrogen bonding in the rapamycin/FKBP-12 complex, and argues that a
`person of ordinary skill in the art would therefore have avoided substitutions
`at C40. Prelim. Resp. 30 (citing Ex. 1006, 7434). Similarly, Novartis notes
`that the prior art at the time of the invention contained numerous examples
`14
`
`
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`of modifications to rapamycin at sites other than the C10, C28, and C40
`hydroxyl groups, suggesting that Dr. Jorgensen’s testimony that a person of
`ordinary skill in the art would have looked only to those sites for
`modification is incorrect. Id. at 28–29. As a final example, Novartis argues
`that there is no reasonable expectation of success, as a person of ordinary
`skill in the art would not have expected everolimus to have the “unique
`combination of properties it possesses.” Id. at 36–40.
`In addition, Novartis provides evidence of objective indicia of non-
`obviousness. Novartis cites the commercial success and industry praise
`achieved by its Afinitor product, which incorporates everolimus as its active
`ingredient. Id. at 47–48. Afinitor is also said to have demonstrated
`unexpected results in anti-tumor effectiveness, especially for renal cell
`carcinoma. Id. at 46.
`We have considered these and other arguments raised by Novartis in
`the Preliminary Response, but do not consider them sufficient to persuade us
`that Par has not established a reasonable likelihood of prevailing in
`challenging claims 1–3 and 10. At most, Novartis’ arguments cast doubt on
`some elements of Par’s lead compound analysis, or create a genuine issue of
`material fact. The parties will have the opportunity to further develop these
`facts during trial, and the Board will evaluate the fully developed record at
`the close of the evidence.
`
`C. Obviousness Over Morris, Van Duyne, Rossmann,
`Yalkowski, Lemke, and Hughes
`Par contends that claims 8 and 9 are unpatentable under 35 U.S.C.
`§ 103(a), as their subject matter would have been obvious over the combined
`
`
`
`15
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`disclosures of Morris, Van Duyne, Rossmann, Yalkowski, Lemke, and
`Hughes. Pet. 48–51. Claim 8 recites a method of inducing an
`immunosuppressant effect using a compound of claim 1, while claim 9 is
`directed to a method of preventing allograft rejection using a compound of
`claim 1. Par alleges that these claims recite applications that were known to
`be associated with the activity of rapamycin; therefore, the derivatives
`obtained as part of the lead compound analysis described above would have
`been expected to have similar activity. Id. at 48–49. Par cites Hughes as
`teaching that rapamycin derivatives, and in particular C40-substituted
`rapamycin, were known to have immunosuppressant activity, including the
`ability to prevent allograft rejection. Id. at 50; Ex. 1009, 4:15–17 and 4:48–
`50. From this, Par concludes that a person of ordinary skill in the art would
`have had reason to use everolimus to provide an immunosuppressant effect
`or to prevent allograft rejection. Pet. 50–51.
`Novartis repeats its arguments regarding Par’s lead compound
`analysis, and contends that Hughes does not remedy any of these
`deficiencies. Prelim. Resp. 50–52. Novartis also contests Par’s
`interpretation of the disclosure of Hughes, arguing that, for example, the
`compound of Example 2 (which Par indicates has immunosuppressant
`activity) was not tested in any in vivo assay. Id. at 51. Again, we consider
`Novartis’ arguments to go to the weight of the evidence, but do not persuade
`us that Par has failed to establish a reasonable likelihood of success. The
`Petition and supporting evidence establish a reasonable likelihood that Par
`will be able to demonstrate that claims 8 and 9 of the ’772 patent would have
`been obvious.
`
`
`
`16
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`D. Remaining Grounds of Unpatentability
`
`Par articulates two additional grounds of unpatentability, which cover
`claims 1–3 and 10, and 8–9, respectively. Pet. 51–54. These grounds
`generally repeat Par’s lead compound analysis, but instead of relying on
`Rossmann, Par cites “the routine use of computer-aided drug design
`software.” Id. We fail to see how these grounds differ appreciably from the
`first two grounds proffered by Par, or how the lead compound analysis
`changes in any significant way by relying on the cited computer-aided drug
`design software. As we have already decided to institute trial on two
`grounds, institution of trial on these additional grounds would complicate the
`proceeding, reducing efficiency and using limited Board and party resources
`without achieving any discernable benefit. We, therefore, exercise our
`discretion to deny institution of these grounds.
`
`III. CONCLUSION
`
`For the foregoing reasons, we conclude that the information presented
`in the Petition and Preliminary Response establishes that there is a
`reasonable likelihood that Par will prevail in challenging at least one claim
`of the ’772 patent as unpatentable under § 103(a).
`
`
`IV. ORDER
`
`Accordingly, it is:
`ORDERED that, pursuant to 35 U.S.C. § 314(a), an inter partes
`review is instituted as to claims 1–3 and 8–10 of U.S. Patent No. 5,665,772
`on the following grounds of unpatentability:
`
`
`
`17
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`
`1. Whether claims 1–3 and 10 are unpatentable under 35 U.S.C.
`§ 103(a) as having been obvious over Morris, Van Duyne,
`Rossmann, Yalkowski, and Lemke; and
`
`2. Whether claims 8 and 9 are unpatentable under 35 U.S.C.
`§ 103(a) as having been obvious over Morris, Van Duyne,
`Rossmann, Yalkowski, Lemke, and Hughes;
`
`FURTHER ORDERED that no other ground of unpatentability, with
`respect to any claim, is instituted for trial; and
`FURTHER ORDERED that pursuant to 35 U.S.C. § 314(c) and 37 C.F.R.
`§ 42.4, notice is hereby given of the institution of a trial, which commences
`on the entry date of this Decision.
`
`
`
`18
`
`
`
`IPR2016-00084
`Patent 5,665,772
`
`FOR PETITIONER:
`Daniel Brown
`Daniel.Brown@lw.com
`Robert Steinberg
`Bob.Steinberg@lw.com
`LATHAM & WATKINS LLP
`
`
`FOR PATENT OWNER:
`Nicholas N. Kallas
`nkallas@fchs.com
`Raymond Mandra
`rmandra@fchs.com
`FITZPATRICK, CELLA, HARPER & SCINTO
`
`
`
`
`
`
`
`
`
`
`
`
`
`19
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
