By: Vivek Ganti (vg@hkw-law.com) (Reg. No. 71,368); and
`
`Sharad Bijanki (sb@hkw-law.com) (Reg. No. 73,400)
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_________________
`
`COMPLEX INNOVATIONS, LLC,
`Petitioner,
`
`v.
`
`AMGEN INCORPORATED
`
`Patent Owner
`
`_________________
`
`U.S. Patent 7,829,595
`
`_________________
`
`PETITION FOR INTER PARTES
`REVIEW OF U.S. PATENT NO. 7,829,595
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`TABLE OF CONTENTS
`TABLE OF AUTHORITIES ................................................................................... iv
`
`I.
`
`Introduction .......................................................................................................... 1
`
`II. Overview .......................................................................................................... 1
`
` Description of the 595 Patent ........................................................................ 1
`
`III. Mandatory Notices (37 C.F.R. § 42.8(a)(1)) .................................................... 4
`
` Notice of related matters (37 C.F.R. § 42.8(b)(2))........................................ 4
`
` Real party-in-interest (37 C.F.R. § 42.8(b)(1)) ............................................. 5
`
`IV. Notice of Counsel and Service Information (37 C.F.R. § 42.8(b)(3-4)) .......... 5
`
`V. Grounds for Standing ....................................................................................... 6
`
`VI. Statement of Relief Requested ......................................................................... 6
`
`VII. Claim Construction ........................................................................................ 6
`
` Applicable Principles of Claim Construction. .............................................. 6
`
`
`
`Level of Skill in the Art ................................................................................. 6
`
`VIII.
`
`Identification of Challenge (37 C.F.R. § 42.104(b)) ..................................... 7
`
`A. Ground 1: Claims Relating to the Formulation and Use of the Active
`
`Pharmaceutical Ingredient (1-25) .........................................................................10
`
`1. Independent Claim 1 ...................................................................................14
`
`
`
`i
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`2. Dependent Claim 2 ......................................................................................17
`
`3. Dependent Claim 3 ......................................................................................18
`
`4. Dependent Claim 4 ......................................................................................18
`
`5. Dependent Claim 5 ......................................................................................19
`
`6. Dependent Claim 6 ......................................................................................19
`
`7. Dependent Claim 7 ......................................................................................20
`
`8. Dependent Claim 8 ......................................................................................21
`
`9. Dependent Claim 9 ......................................................................................21
`
`10. Dependent Claim 10 .................................................................................22
`
`11. Dependent Claim 11 .................................................................................22
`
`12. Dependent Claim 12 .................................................................................23
`
`13. Dependent Claim 13 .................................................................................24
`
`14. Dependent Claim 14 .................................................................................25
`
`15. Dependent Claim 15 .................................................................................25
`
`16. Dependent Claim 16 .................................................................................26
`
`17. Dependent Claim 17 .................................................................................27
`
`18. Dependent Claim 18 .................................................................................27
`
`ii
`
`
`
`
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`19. Dependent Claim 19 .................................................................................28
`
`20. Dependent Claim 20 .................................................................................28
`
`21. Dependent Claim 21 .................................................................................29
`
`22. Dependent Claim 22 .................................................................................30
`
`23. Dependent Claim 23 .................................................................................30
`
`24. Dependent Claim 24 .................................................................................31
`
`25. Dependent Claim 25 .................................................................................32
`
`IX. No Secondary Conditions Exist .....................................................................32
`
`X.
`
`Fees (37 C.F.R. § 42.103) ...............................................................................32
`
`XI. Conclusion ......................................................................................................33
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`iii
`
`

`

`
`
`Case Law
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`TABLE OF AUTHORITIES
`
`Page
`
`Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 739 (Fed. Cir. 2013), cert.
`
`denied, 134 S. Ct. 2740 (2014) ............................................................................... 9
`
`Graham v. John Deere Co., 383 U.S. 1 (1966) ......................................................... 9
`
`In re Kahn, 441 F.3d 977, 987-88 (Fed. Cir. 2006) ................................................... 9
`
`KSR v. Teleflex, 550 U.S. 398 (2007) ................................................... 8-9, 13, 16-17
`
`Statutes
`
`35 U.S.C. § 102(a) ............................................................................................. 10-11
`
`35 U.S.C. § 103 .................................................................................... 1, 9, 13, 17-32
`
`35 U.S.C. § 103(a) ..................................................................................................... 8
`
`35 U.S.C. § 314(a) ...................................................................................................33
`
`37 C.F.R. § 42.6(d) .................................................................................................... 7
`
`37 C.F.R. § 42.8(a)(1) ................................................................................................ 4
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 5
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 4
`
`37 C.F.R. § 42.8(b)(3-4) ............................................................................................ 5
`
`37 C.F.R. § 42.10(b) .................................................................................................. 5
`
`37 C.F.R. § 42.15(a) .................................................................................................33
`
`37 C.F.R. § 42.100(b) ................................................................................................ 6
`iv
`
`
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`37 C.F.R. § 42.103 ...................................................................................................32
`
`37 C.F.R. § 42.104(b) ................................................................................................ 7
`
`
`
`
`
`
`
`v
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`EXHIBIT LIST
`Ex. 1001 U.S. Patent No. 7,829,595 to Lawrence, et al. (“595 Patent” or “Ex.
`
`1001”)
`
`Ex. 1002
`
`File History to the 595 Patent (“File History” or “Ex. 1002”)
`
`Ex. 1003 U.S. Patent No. 6,211,244 to Van Wagenen, et al. (“Van Wagenen” or
`
`“Ex. 1003”)
`
`Ex. 1004 U.S. Patent No. 5,162,117 to Stupak, et al. (“Stupak” or “Ex. 1004”)
`
`Ex. 1005
`
`European Patent Application No. 1 321 142 A1 by Vitzling, et al.
`
`(“Vitzling” or “Ex. 1005”)
`
`Ex. 1006 U.S. Patent No. 5,879,706 to Carter, et al. (“Carter” or “Ex. 1006”)
`
`Ex. 1007 Canadian Patent Application No. 2,004,565 by Chang, et al. (“Chang”
`
`or “Ex. 1007”)
`
`Ex. 1008 U.S. Patent No. 8,703,196 to Babcock, et al. (“Babcock” or “Ex.
`
`1008”)
`
`Ex. 1009 U.S. Patent No. 6,733,780 to Tyler, et al. (“Tyler” or “Ex. 1009”)
`
`Ex. 1010 U.S. Patent No. 4,931,286 to Johnson, et al. (“Johnson” or “Ex.
`
`1010”)
`
`Ex. 1011
`
`Excerpts from The Pharmaceutical Codex: Principles and Practice of
`
`Pharmaceutics (12th ed.) (1994) (“Pharmaceutical Codex” or “Ex.
`
`1011”)
`
`
`
`vi
`
`

`

`
`Ex. 1012
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`Excerpts from the Handbook of Pharmaceutical Excipients (3rd ed.)
`
`(2000) (“HPE” or “Ex. 1012”)
`
`Ex. 1013
`
`Excerpts from Howard C. Ansel, et al., Pharmaceutical Dosage Forms
`
`and Drug Delivery Systems (7th ed.) (1999) (“Ansel” or “Ex. 1013”)
`
`Ex. 1014
`
`Excerpts from Herbert A. Lieberman, Leon Lachman, Joseph B.
`
`Schwartz (eds.), Pharmaceutical Dosage Forms: Tablets (2nd ed.)
`
`(1989) Vol. 1 (“Lieberman I” or “Ex. 1014”)
`
`Ex. 1015
`
`Excerpts from Herbert A. Lieberman, Leon Lachman, Joseph B.
`
`Schwartz (eds.), Pharmaceutical Dosage Forms: Tablets (2nd ed.)
`
`(1989) Vol. 2 (“Lieberman II” or “Ex. 1015”)
`
`Ex. 1016
`
`Particle Size – U.S. Sieve Series and Tyler Mesh Series Equivalents
`
`(2002; updated 2013), found at
`
`www.azom.com/article.aspx?ArticleID=1417, last accessed August 7,
`
`2015 (“Particle Size” or “Ex. 1016”)
`
`Ex. 1017 New Agent Reduces PTH Levels in Hemodialysis Patients With
`
`Secondary Hyperparathyroidism, FORMULARY (April 2003) Vol. 38,
`
`p. 197 (“Formulary” or “Ex. 1017”)
`
`Ex. 1018
`
`J.C. Chaumeil, Micronization: A Method of Improving the
`
`Bioavailability of Poorly Soluble Drugs, METH. FIND. EXP. CLIN.
`
`PHARMACOL. (1998), pp. 211-215 (“Chaumeil” or “Ex. 1018”)
`
`
`
`vii
`
`

`

`
`Ex. 1019
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`Excerpt from Sir Colin Dollery (ed.), Therapeutic Drugs, (1991) Vol.
`
`2 (“Dollery” or “Ex. 1019”)
`
`Ex. 1020 Gordon T. McInnes, et al., Effect of Micronization on the
`
`Bioavailability and Pharmacologic Activity of Spironolactone, J.
`
`CLIN. PHARMACOL. 22 (1982), pp. 410-417 (“McInnes” or “Ex.
`
`1020”)
`
`Ex. 1021 Declaration of Walter G. Chambliss, Ph.D. (“Ex. 1021”)
`
`Ex. 1022 Decision Granting Inter Partes Review as to U.S. Patent No.
`
`6,821,975 (“Ex. 1022”)
`
`Ex. 1023 Declaration of Jennifer L. Calvert (“Ex. 1023”)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`viii
`
`

`

`
`I.
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`Introduction
`Complex Innovations, LLC (“Petitioner”) petitions for inter partes review
`
`seeking cancellation of claims 1-25 of U.S. Pat. No. 7,829,595 (“the 595 Patent,”
`
`Ex. 1001), which is assigned to Amgen Incorporated (“Amgen”). Amgen is referred
`
`to as “Patent Owner” in this Petition.
`
`II. Overview
`This Petition furthers the purpose of inter partes review – the cancellation of
`
`unpatentable claims. The challenged claims 1-25 of the 595 Patent never should have
`
`issued. This Petition establishes a reasonable likelihood that Petitioner will prevail
`
`regarding at least one of the claims challenged and that the challenged claims are
`
`unpatentable under pre-AIA 35 U.S.C. § 103. Thus, Petitioner respectfully requests
`
`that the Board grant the Petition and institute trial on all of the challenged claims.
`
` Description of the 595 Patent
`The 595 Patent issued on November 9, 2010, and appears to claim priority to
`
`September 12, 2003. (Ex. 1001, p.1). The Abstract of the patent describes the
`
`invention as a “pharmaceutical composition comprising a therapeutically effective
`
`amount of a calcium receptor-active compound and at least one pharmaceutically
`
`acceptable excipient, wherein the composition has a controlled dissolution profile.”
`
`(Id., abstract). The 595 Patent also includes method claims for treating diseases in
`
`humans, including hyperparathyroidism, using the disclosed pharmaceutical
`
`composition. (Id., abstract & claims 24-25).
`1
`
`
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`More specifically, the 595 Patent describes a pharmaceutical composition
`
`comprising cinacalcet hydrochloride in combination with excipients commonly used
`
`in pharmaceutical formulations. (Id., claim 1 & Examples at col. 11-13).
`
`The Patent Office rejected the claims in the 595 Patent application on several
`
`occasions for various reasons, including that many were anticipated by or
`
`unpatentable over certain prior art, ultimately requiring the Applicants to amend the
`
`claims multiple times. (Ex. 1002 – Non-Final Rejection, July 23, 2007 (pp.1315-
`
`1325); Amendment, December 21, 2007 (pp. 1333-1346); Final Rejection, April 14,
`
`2008 (pp.1374-1385); Amendment, July 14, 2008 (pp. 1412-1423); Amendment,
`
`December 23, 2008 (pp. 1434-1442); Non-Final Rejection, April 30, 2009 (pp. 1444-
`
`1452); Amendment, July 24, 2009 (pp. 1470-1478).
`
`Notably, the Applicants repeatedly argued non-obviousness based on the
`
`unique dissolution profile disclosed in the 595 Patent application. (See generally id.)
`
`The 595 Patent Applicants also argued that the claims were patentable over prior art
`
`because a Person of Ordinary Skill in the Art (POSITA) would not have the
`
`expectation of formulating cinacalcet hydrochloride as taught by the 595 Patent
`
`application in light of the poor water solubility of cinacalcet hydrochloride, which
`
`“limits options for formulations and can adversely impact the bioavailability...” (Ex.
`
`1002, p. 1441 – Amendment, December 23, 2008).
`
`
`
`2
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`The Patent Office ultimately allowed certain claims; however, all of the claims
`
`are taught by prior art and the general knowledge of a person of ordinary skill in the
`
`art (“POSITA”). (See generally Ex. 1021). In particular, the 595 Patent admits that
`
`cinacalcet hydrochloride was known in the art. (Ex. 1001, col. 1, lines 7-10 &
`
`Certificate of Correction at p.10) (“Calcium receptor-active compounds are known
`
`in the art. One example of a calcium receptor-active compound is cinacalcet HCl,
`
`which is described, for example, in U.S. Pat. No. 6,211,244 [Ex. 1003 or “Van
`
`Wagenen”]”). Van Wagenen also teaches pharmaceutical compositions containing
`
`an active pharmaceutical ingredient (“API”), such as cinacalcet hydrochloride, and
`
`acceptable carriers (otherwise known as excipients). (See Ex. 1003, col. 5, lines 26-
`
`35). Van Wagenen states:
`
`Suitable dosage ranges, formulations, and dosage forms for other
`compounds described herein can also be determined by one skilled in
`the art based on the teachings provided in the application.
`
`(Id., col. 44, lines 42-45). Further, it was known to treat hyperparathyroidism with
`
`such a pharmaceutical composition comprising a therapeutically effective amount of
`
`an inorganic ion receptor-modulating agent such as cinacalcet hydrochloride. (Id.,
`
`col. 5, line 48 – col. 6, line 18).
`
`Finally, none of the 595 Patent claims reference a “dissolution profile” that
`
`the Applicants so heavily stressed during prosecution (see Ex. 1001, claims 1-25;
`
`see generally Ex. 1002), and, contrary to the 595 Patent Applicants’ assertions, it
`
`
`
`3
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`was well known in the art to develop successful pharmaceutical formulations
`
`containing APIs with poor water solubility. (Ex. 1021 at ¶ 40-42).
`
`This Petition shows that the challenged claims of the 595 Patent are rendered
`
`obvious by various combinations of Van Wagenen (Ex. 1003), the Handbook of
`
`Pharmaceutical Excipients (the “HPE”) (Ex. 1012), and the knowledge of a
`
`POSITA, as further supported by representative prior art references including:
`
`Stupak (Ex. 1004); Vitzling (Ex. 1005); Carter (Ex. 1006); Chang (Ex. 1007);
`
`Babcock (Ex. 1008); Tyler (Ex. 1009); Johnson (Ex. 1010); the Pharmaceutical
`
`Codex (Ex. 1011); Ansel (Ex. 1013); Lieberman I (Ex. 1014); and Lieberman II (Ex.
`
`1015).
`
`Walter Chambliss, Ph.D., a formulations expert in the pharmaceutical field
`
`for over thirty-five years, explains how Van Wagenen, the HPE and the general
`
`knowledge of a POSITA, as represented in various prior art references, disclose,
`
`teach and otherwise suggest every feature of the challenged claims and how each of
`
`the challenged claims was obvious to a POSITA as of September 12, 2003. (Ex.
`
`1021). As Dr. Chambliss explains, the challenged claims of the 595 are unpatentable.
`
`(Id.). In view of the evidence, the Board should cancel all of the challenged claims.
`
`III. Mandatory Notices (37 C.F.R. § 42.8(a)(1))
` Notice of related matters (37 C.F.R. § 42.8(b)(2))
`None.
`
`
`
`4
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
` Real party-in-interest (37 C.F.R. § 42.8(b)(1))
`The real parties in interest are:
`
`• Complex Innovations, LLC (California limited liability company,
`
`principal place of business at 101 First Street, Suite 711, Los Altos,
`
`California 94022).
`
`IV. Notice of Counsel and Service Information (37 C.F.R. § 42.8(b)(3-4))
`Lead Counsel: Vivek Ganti (Reg. No. 71,368)
`
`
`
`Address: HILL, KERTSCHER & WHARTON, LLP, 3350 Riverwood
`
`Parkway, Suite 800, Atlanta, GA 30339. Tel. 678.384.7453. Fax. 770.953.1358.
`
`Backup Counsel: Sharad Bijanki (Reg. No. 73,400)
`
`
`
`Address: HILL, KERTSCHER & WHARTON, LLP, 3350 Riverwood
`
`Parkway, Suite 800, Atlanta, GA 30339. Tel. 678.384.7448. Fax. 770.953.1358.
`
`
`
`Please address all correspondence to the lead counsel at the address shown
`
`above. Petitioner consents to electronic service of papers by email at: vg@hkw-
`
`law.com and sb@hkw-law.com.
`
`Pursuant to 37 C.F.R. § 42.10(b), a Power of Attorney by Petitioner
`
`appointing each of the above designated counsel and additional counsel is
`
`concurrently filed.
`
`
`
`5
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`V. Grounds for Standing
`Petitioner certifies that the 595 Patent is eligible for inter partes review and
`
`that the Petitioner is not estopped or barred from requesting inter partes review
`
`challenging the claims identified in the Petition. The required fee is paid via online
`
`using Deposit Account No. 506541 (Customer ID No. 87296). The Office is
`
`authorized to charge fee deficiencies and credit overpayments to this Deposit
`
`Account No. 506541.
`
`VI.
`
`Statement of Relief Requested
`Petitioner requests inter partes review and cancellation of claims 1-25 of the
`
`595 Patent based on the detailed statements presented in Sections VII and VIII.
`
`VII. Claim Construction
` Applicable Principles of Claim Construction.
`All claim terms employ their plain and ordinary meanings. The Board should
`
`construe these claims using the broadest reasonable interpretation (“BRI”). See 37
`
`C.F.R. § 42.100(b). A POSITA for the challenged claims would appreciate that the
`
`claim terms in the 595 Patent should be given their plain and ordinary meaning (Ex.
`
`1021, ¶ 14).
`
`Level of Skill in the Art
`
`
`With respect to the 595 Patent, the claims generally implicate issues relating
`
`to pharmaceutics (i.e., the formulation of the API). The POSITA is therefore a person
`
`holding a Bachelor of Science degree (or an equivalent) in chemistry, pharmacy or
`
`
`
`6
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
` related field with at least two years of relevant experience in pharmaceutical drug
`
` a
`
`development, including formulation work. (Id., ¶ 13).
`
`VIII.
`
`Identification of Challenge (37 C.F.R. § 42.104(b))
`
`Petitioner requests IPR on the one Ground of Unpatentability noted below. In
`
`accordance with 37 C.F.R. § 42.6(d), copies of the references listed in the table of
`
`the claims of the 595 Patent below are filed with this Petition. Additional references
`
`serving as further proof of unpatentability are also filed with this Petition. (Exs.
`
`1004-1011 & 1013-1015).
`
`GROUND
`
`
`
`Claims of the
`595 Patent
`1-25
`
`Prior Art & The General Knowledge of POSITA That
`Renders the Claims Obvious
`Van Wagenen (Ex. 1003), the HPE (Ex. 1012), & the general
`knowledge of a POSITA
`
`
`As further support for the Ground of Unpatentability, Petitioner submits the
`
`accompanying declaration of technical expert Walter Chambliss, Ph.D. (Ex. 1021),
`
`which explains how a POSITA would understand the art and the general knowledge
`
`a POSITA possesses.
`
`Dr. Chambliss is highly qualified to analyze the knowledge of a POSITA and
`
`the pertinent prior art relating to the cinacalcet hydrochloride composition, and how
`
`the POSITA’s general knowledge together with the prior art renders claims 1-25
`
`unpatentable. As set forth in his declaration, Dr. Chambliss holds a Ph.D. in
`
`Pharmaceutics from the University of Mississippi (1982), as well as a Master of
`7
`
`
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`Science in Pharmaceutics (1980) and Bachelor of Science in Pharmacy (1977) from
`
`the University of Mississippi. Dr. Chambliss is currently the Director of Technology
`
`Management, a Research Professor with the Research Institute of Pharmaceutical
`
`Sciences, and a Pharmaceutics Professor at the University of Mississippi, where he
`
`has been a faculty member since 1999. In addition, Dr. Chambliss has industry
`
`experience, helping launch approximately thirty (30) new or improved drugs per
`
`year over eleven (11) years with Schering-Plough Healthcare Products. After
`
`reviewing the 595 Patent as well the prior art referenced in this Petition, Dr.
`
`Chambliss opines that challenged claims 1-25 are unpatentable because they were
`
`obvious to a POSITA at the time of invention.
`
`The ground upon which this Petition is based is summarized as follows:
`
`Ground 1: The combination of a POSITA’s general knowledge, Van
`
`Wagenen (Ex. 1003), and the HPE (Ex. 1012) render obvious claims 1 – 25 under
`
`35 U.S.C. § 103(a).
`
`Dr. Chambliss independently has considered and validated the elements of the
`
`prior art at issue in this ground in order to ensure that the prior art was within the
`
`knowledge of a POSITA at the time of invention.
`
`A POSITA is presumed to be aware of all pertinent art, thinks in accordance
`
`with the conventional wisdom of the art, and is a person of ordinary creativity. (KSR
`
`v. Teleflex, 550 U.S. 398, 420 (2007)).
`
`
`
`8
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`“The combination of familiar elements according to known methods is likely
`
`to be obvious when it does no more than yield predictable results.” (KSR, 550 U.S.
`
`at 416). In Graham v. John Deere Co., 383 U.S. 1 (1966), the United States Supreme
`
`Court clarified the nonobviousness requirement in United States patent law, set forth
`
`in 35 U.S.C. § 103. The Court held that Section 103 requires a determination of the
`
`scope and content of the prior art, the differences between the claimed invention and
`
`the prior art, and the level of ordinary skill in the prior art. (Graham, 383 U.S. at 17-
`
`18). In addition, “secondary considerations” may, in appropriate cases, serve as
`
`evidence of nonobviousness. (Id.) A basis to combine teachings from the references
`
`need not be stated expressly in any prior art reference. (In re Kahn, 441 F.3d 977,
`
`987-88 (Fed. Cir. 2006)). There need only be an articulated reasoning with rational
`
`underpinnings to support a motivation to combine teachings. (Id. at 988).
`
`With respect to claim terms referring to ranges, where a range is disclosed in
`
`prior art, and the claimed invention falls within that range, the burden falls upon the
`
`applicant to establish non-obviousness. (Galderma Labs., L.P. v. Tolmar, Inc., 737
`
`F.3d 731, 739 (Fed. Cir. 2013), cert denied, 134 S. Ct. 2740 (2014)). Further,
`
`“[u]nexpected results that are probative of nonobviousness are those that are
`
`‘different in kind and not merely in degree from the results of the prior art.’ Results
`
`which differ by percentage are differences in degree rather than kind, where the
`
`
`
`9
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`modification of the percentage is within the capabilities of [a POSITA].” (Id.
`
`(citation omitted)).
`
`A. Ground 1: Claims Relating to the Formulation and Use of the
`Active Pharmaceutical Ingredient (1-25)
`
`The 595 Patent claims the formulation of a known drug (cinacalcet
`
`hydrochloride) with excipients and within standard ranges and ratios well known to
`
`a formulator. There is a total absence of grounds to support patentability. Petitioner
`
`cites to only a representative sample of the many prior art references that support
`
`this petition.
`
`Van Wagenen is a U.S. Patent filed on October 23, 1995 and issued on April
`
`3, 2001 (Ex. 1003). Van Wagenen is prior art under at least 35 U.S.C. § 102(a) and
`
`102(b). HPE refers to a third edition of the Handbook of Pharmaceutical Excipients,
`
`a printed publication that constitutes prior art under 35 U.S.C. § 102(b) for being
`
`publically available as of the year 2000.
`
`The PTAB has held that “[w]hen determining the threshold issue of whether
`
`a document is a printed publication for purposes of a decision on institution, a
`
`copyright notice has been accepted a prima facie evidence of publication. See Ford
`
`Motor Co. v. Cruise Control Techs. LLC, Case IPR2014-00291, slip op. at 7–8
`
`(PTAB June 29, 2015) (Paper 44) (citing FLIR Sys., Inc. v. Leak Surveys, Inc., Case
`
`IPR2014-00411, slip op. at 18–19 (PTAB Sept. 5, 2014) (Paper 9)).” (LG
`
`Electronics, INC. v. Advanced Micro Devices, Inc., IPR2015-00329, paper 13, p.12
`
`
`
`10
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`(PTAB July 10, 2015)). Here, the HPE bears a copyright notice of the year 2000
`
`and is thus, publically available as of 2000. (Ex. 1012, p. 2).
`
`Even further, the HPE is a book that was publically available in the British
`
`Library. (Id.). The HPE is labeled with two Internal Standard Book Numbers
`
`(ISBNs): one for the U.S. (0-85369-381-1) and one for the United Kingdom (0-
`
`917330-96-X). “An ISBN number uniquely identifies your book, and facilitates the
`
`sale of your book to bookstores (physical and digital) and libraries.” (See
`
`http://www.isbn.org/.) These facts establish a prima facie case that the HPE is a
`
`printed book that was made publically available as of 2000 in at least in the United
`
`States and the United Kingdom.
`
`While Van Wagenen was considered by the examiner, it was not considered
`
`in combination with the HPE during prosecution of the 595 Patent. Indeed, the HPE
`
`was not considered by the examiner at all. Further, none of the additional supporting
`
`references (Stupak, Vitzling, Carter, Chang, Babcock, Tyler, Johnson, the
`
`Pharmaceutical Codex, Ansel, Lieberman I, and Lieberman II) were considered by
`
`the examiner during prosecution.
`
`Stupak, Vitzling, Carter, Chang, Babcock, Tyler, Johnson, the Pharmaceutical
`
`Codex, Ansel, Lieberman I and Lieberman II are all prior art under at least 35 U.S.C.
`
`§ 102(a). Given the legal standard noted above, the 595 Patent represents obvious
`
`ways to combine the general knowledge of a POSITA, Van Wagenen, and the HPE.
`
`
`
`11
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`As detailed in the Chambliss Declaration (Ex. 1021), at the time of the
`
`invention (and currently) development of pharmaceutical compositions involved
`
`combining a promising therapeutic chemical compound (or “API”) with one or more
`
`inactive ingredients (or “excipients”) to create a dosage form, such as a tablet or
`
`capsule for oral administration. (Ex. 1021, ¶ 19). The goal in developing oral dosages
`
`is to create a stable formulation that will release the API in the patients’
`
`gastrointestinal tract at the desired rate that can be manufactured and sold on a
`
`commercial level, and also can be self-administered by patients. (Id., ¶ 20). APIs are
`
`mixed with excipients and tested under accelerated conditions. (Id., ¶ 26). A
`
`formulator can choose excipients to test based on results of prior excipient-
`
`compatibility studies, as well as her own general knowledge of the functions of
`
`excipients commonly used in oral dosages. (Id.). Further, a formulator will optimize
`
`the particle size range for the API during preformulation studies and routine
`
`optimization. (Id., ¶ 28). Indeed, as previously recognized by the Patent Trial and
`
`Appeals Board, reducing particle size to improve dissolution rate was and is a
`
`conventional method known in the art. (Ex. 1022 at p. 18.)
`
`The various excipients, formulations of the API and excipient(s) (and ranges
`
`thereof), and methods for treatment using the formulations in challenged claims 1-
`
`25 were well known at the time of the invention as demonstrated by their disclosure
`
`in the prior art references listed in the immediately preceding paragraph. (See, e.g.,
`
`
`
`12
`
`

`

`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`
`Ex. 1021, ¶ 73). “Suitable dosage ranges, formulations, and dosage forms” can be
`
`“determined by one skilled in art…” (Ex. 1003, col. 44, lines 42-45). A POSITA
`
`would have been motivated by his/her general knowledge, Van Wagenen, and the
`
`HPE to formulate cinacalcet hydrochloride with well-known excipients in a manner
`
`that would yield an expected result. (Ex. 1021, ¶¶ 75-77, 94-96).
`
`Further, the Applicants cannot meet their burden to show that the claimed sub-
`
`ranges and sub-ratios disclosed in the 595 Patent are non-obvious. Neither the 595
`
`Patent specification nor file history discloses or teaches anything special or
`
`advantageous relating to the sub-ranges and sub-ratios taught by the claims.
`
`Accordingly, because these sub-ranges and sub-ratios only differ by percentage, they
`
`are only differences in degree, rather than kind, and are thus unpatentable.
`
`Applying the combination of the general knowledge of a POSITA, Van
`
`Wagenen, and the HPE (as further supported by, Stupak, Vitzling, Carter, Chang,
`
`Babcock, Tyler, Johnson, Ansel, the Pharmaceutical Codex, Lieberman I and/or
`
`Lieberman II) to the challenged claims 1-25 renders the claims unpatentable under
`
`35 U.S.C. § 103 (obviousness). (Ex. 1021, ¶ 73). This ground of unpatentability
`
`demonstrates that the challenged claims of the 595 Patent simply state what already
`
`was known in the field; these claims, if allowed to stand, merely diminish the
`
`resources available to skillful men. (KSR, 550 U.S. at 415-16).
`
`
`
`13
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Pat. No. 7,829,595
`
`Independent Claim 1
`1.
`Independent claim 1 states: “A pharmaceutical composition comprising (a)
`
`from about 10% to about 40% by weight of cinacalcet HCl; (b) from about 40% to
`
`about 75% by weight of microcrystalline cellulose; (c) from about 1% to about 5%
`
`by weight of povidone; (d) from about 5% to about 35% by weight of starch; (e)
`
`from about 1% to about 10% by weight of crospovidone; (f) from about 0.05% to
`
`about 1.5% by weight of colloidal silicon dioxide; and (g) from about 0.05% to about
`
`1.5% by weight of magnesium stearate; wherein the percentage by weight is relative
`
`to the total weight by composition.” (Ex. 1001, col. 14, lines 17-31).
`
`Van Wagenen discloses pharmaceutical compositions containing cinacalcet
`
`hydrochloride. (Ex. 1001, col. 2, lines 18-28). Of note, the 595 Patent admits that
`
`cinacalcet hydrochloride was known in the art and described in Van Wagenen. (Id.,
`
`col. 1, lines 7-10 & Certificate of Correction at p.10). Further, the ranges of the
`
`cinacalcet hydrochloride and excipients disclosed in Claim 1 are common ranges
`
`known to a POSITA. (General Knowledge of POSITA).1 Thus, a POSITA would
`
`
`1 Many of the claim elements in the 595 Patent are within the general knowledge of
`
`a POSITA. Where such claim elements are present, Petitioner cites to “General
`
`Knowledge of POSITA” for support. Dr. Chambliss’ declaration (Ex. 1021) is
`
`based on his own substantial experi