Trials@uspto.gov
`571.272.7822
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`
`
`
` Paper 10
`
` Date: April 27, 2020
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`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PROGENICS PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER
`WISSENSCHAFTEN E.V.
`AND
`UNIVERSITAT ZU KOLN,
`Patent Owners.
`____________
`
`PGR2019-00052
`Patent 10,112,974 B2
`____________
`
`
`Before GEORGIANNA W. BRADEN, J. JOHN LEE, and
`MICHAEL A. VALEK, Administrative Patent Judges.
`
`VALEK, Administrative Patent Judge.
`
`
`
`
`
`JUDGMENT
`Final Written Decision
`Determining No Challenged Claims Unpatentable
`35 U.S.C. § 328(a)
`
`
`
`
`
`
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
` INTRODUCTION
`
`This Final Written Decision is issued pursuant to 35 U.S.C. § 328(a)
`
`and 37 C.F.R. § 42.73. Progenics Pharmaceuticals, Inc., (“Petitioner”) bears
`
`the burden of providing the unpatentability of the challenged claims by a
`
`preponderance of the evidence. 35 U.S.C. § 326(e) (2018). For the reasons
`
`explained below, we determine Petitioner has failed to establish by a
`
`preponderance of the evidence that claims 6, 8, and 10–12 of U.S. Patent
`
`No. 10,112,974 B2 (Ex. 1001, “the ’974 patent”) are unpatentable. Max-
`
`Planck-Gesellschaft zur Foerderung der Wissenschaften e.V. and Universitat
`
`zu Koln (collectively “Patent Owner”) have disclaimed all of the other
`
`claims of the ’974 patent previously at issue in this proceeding.
`
`A.
`
`Procedural Background
`
`Petitioner filed a Petition seeking post-grant review of claims 1–15
`
`and 31 of the ’974 patent. Paper 2 (“Pet.”). Patent Owner did not file a
`
`preliminary response. Upon consideration of the information presented in
`
`the Petition, we determined Petitioner had shown it was more likely than not
`
`that claims 1–5, 7, 9, 13, 15, and 31 were unpatentable for one or more of
`
`the asserted grounds. Paper 7, 35 (“Institution Decision”). We also
`
`explained why we were not persuaded that Petitioner had met its burden
`
`with respect to the other challenged claims. Id. Nevertheless, following SAS
`
`Institute Inc. v. Iancu, 138 S. Ct. 1348 (2018) and USPTO guidance, we
`
`instituted review of all claims challenged under all grounds in the Petition.
`
`Id.
`
`After institution, Patent Owner notified the Board that it intended to
`
`file a statutory disclaimer of claims 1–5, 7, 9, 13, 15, and 31 and was
`
`waiving its opportunity to file a response and motion to amend. Paper 9, 2.
`
`Patent Owner further indicated that it would “not request adverse judgment
`
`2
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`as to Petitioner’s grounds for claims 6, 8, 10–12, and 14.” Id. Thus, we
`
`ordered that “the post grant review will continue as instituted, albeit without
`
`a response or other papers from Patent Owner.” Id.
`
`On March 13, 2020, Patent Owner filed a statutory disclaimer
`
`disclaiming claims 1–5, 7, 9, 13–15, and 31. Ex. 2001. Claims 1–5, 7, 9,
`
`13–15, and 31 are, therefore, no longer at issue in this proceeding. See
`
`35 U.S.C. § 253 (2018) (disclaimer of claims considered effective as if part
`
`of original patent); 37 C.F.R. § 42.207(e) (“No post-grant review will be
`
`instituted on disclaimed claims.”). Claims 6, 8, and 10–12 remain at issue.
`
`Both Petitioner and Patent Owner subsequently confirmed that they
`
`would not request oral argument and did not intend to file any other paper
`
`prior to entry of our Final Written Decision on the remaining claims. As
`
`such, the record is complete and consists of the Petition and accompanying
`
`exhibits Ex. 1001–1033, as well as Patent Owner’s statutory disclaimer (Ex.
`
`2001).
`
`B.
`
`The ’974 Patent
`
`The ’974 patent describes methods and chemical precursors for
`
`making “18F-labelled active esters via nucleophilic substitution of the
`
`corresponding onium precursors with 18F-. . . .” Ex. 1001, Abstr. The
`
`Specification indicates that such compounds are “useful for positron
`
`emission tomography (PET) imaging, especially imaging prostate tumor.”
`
`Id. at 1:14–18. According to the Specification,
`
`In recent years imaging of prostate carcinoma (PCa) with PET
`isotope labelled PSMA ligands has become of considerable
`importance in clinical diagnosis. This can mainly be attributed
`to the high expression of the extracellular localized prostate
`specific membrane antigen (PSMA) in PCa. Ligands bearing
`the syL-C(O)-Glu-binding motif exhibit high binding affinity to
`PSMA.
`
`3
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`Id. at 5:60–66.
`
`The 18F-labelled compounds taught in the Specification exhibit a
`
`“syL-C(O)-Glu” or glutamate-urea-lysine (“GUL”) motif and correspond to
`
`general formula (I), which is reproduced below.
`
`
`
`
`
`Id. at 7:40–55.1 The compounds in formula (II) and formula (III), shown
`
`below, are described in the Specification as precursors used to make
`
`compounds of formula (I) according to the methods therein.
`
`
`
`1 The Specification’s descriptions for the variables depicted in formulas (I),
`(II), and (III) are not reproduced here for sake of brevity.
`
`4
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`
`
`
`
`
`
`
`
`The Specification provides numerous examples of compounds
`
`corresponding to general formula (I) that may be made with the disclosed
`
`methods. See generally id. at 26:11–28:10; 45:45–59:60 (listing
`
`compounds). One of these examples, “[18F]DCFPyL” or compound 1-10 in
`
`the Specification, is shown below.
`
`
`
`5
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`The Specification acknowledges that a method for making [18F]DCFPyL
`
`was known in the prior art, but describes certain “disadvantages” to that
`
`method. See id. 5:66–7:20 (citing “Pomper et al. (WO2010/01493; Clin.
`
`Cancer Res. 2011, 17, 7645-7653) (“Pomper”)). According to the
`
`Specification, the methods described therein involve the use of compounds
`
`corresponding to formula (II) and formula (III) as precursors and provide
`
`advantages over the prior art method in Pomper. See id. at 62:54–64:8
`
`(describing “Scheme 6: The novel method for the preparation of
`
`[18F]DCFPyL 1–10” and comparing it to “the published radiosynthesis of
`
`[18F]DCFPyL 1–10 by Pomper et al.”).
`
`C.
`
`Illustrative Claim
`
`Claims 6, 8, and 10–12 depend from claim 1 and, therefore,
`
`incorporate the limitations of claim 1 as recited below:
`
`A compound of formula (II)
`
`1.
`
`
`
`
`wherein, E represents a covalent bond or
`
`
`
`
`
`
`
`
`
`6
`
`

`

`PGR2019-00052
`PGR2019-00052
`Patent 10,112,974 B2
`Patent 10,112,974 B2
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`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`
`
`
`
`
`
`
`wherein
`
`n is an integer selected from 0 to 10;
`
`n1 is an integer selected from 0 to 10;
`
`n2 is an integer selected from 0 to 10;
`
`m is an integer selected from 1 to 18;
`
`p is an integer selected from 0 to 10;
`
`q is an integer selected from 1 to 18;
`
`X, Y, W, and Z represent independently of each other
` ––CH2––, ––CH––, ––NH–– or ––N––;
`
`
` represents a single or double bond;
`and diastereomers, entantiomers, hydrates, and salts
`thereof.
`
`
`Ex. 1001, 101:25–103:25. Each of claims 6, 8, and 10–12 recite an
`
`additional limitation narrowing the range of integers for certain variables
`
`recited in claim 1. See id. at 108:38–55. The text of these claims, as they
`
`appear in the ’974 patent, is reproduced below.
`
`The compound according to claim 1, wherein either of n
`6.
`or n1 or n2 is an integer selected from 1 or 2.
`
`The compound according to claim 1, wherein either of m
`8.
`is an integer selected from 1 to 4.
`
`8
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`10. The compound according to claim 1, wherein either of p
`is an integer selected from 0, 2 to 4.
`
`11. The compound according to claim 1, wherein either of q
`is an integer selected from 1 to 10.
`
`12. The compound according to claim 1, wherein either of q
`is an integer selected from 1 to 3.
`
`Id.
`
`D.
`
`The Asserted Grounds of Unpatentability
`
`Petitioner asserted the following grounds in the Petition (Pet. 29–30):
`
`Claim(s) Challenged
`
`
`
`35 U.S.C. §
`
`Reference(s)/Basis
`
`1, 3–15, 31
`
`2
`
`3, 4, 15
`
`1–4, 9, 13, 15
`
`1–5, 7, 9, 11, 12, 15
`
`1–4, 9, 13, 15
`
`5–8, 10–12, 14
`
`31
`
`112(b)
`
`112(b)
`
`112(d)
`
`102
`
`102
`
`102
`
`103
`
`103
`
`Indefiniteness
`
`Indefiniteness
`
`
`
`’192 publication2
`
`Shallal3
`
`’529 publication4
`
`’529 publication
`
`’933 publication5
`
`
`
`2 WO2008/058192 A2, published May 15, 2008 (“’192 publication”)
`(Ex. 1004).
`3 Hassan M. Shallal et al., Heterobivalent Agents Targeting PSMA and
`Integrin-αvβ3, Bioconjugate Chem., Vol. 25, 393–405 (2014) (“Shallal”)
`(Ex. 1005).
`4 WO2009/002529 A2, published Dec. 31, 2008 (“’529 publication”)
`(Ex. 1006).
`5 WO2010/014933 A2, published Feb. 4, 2010 (“’933 publication”)
`(Ex. 1007).
`
`9
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`1–12, 14, 15
`
`112(a)
`
`Enablement
`
`Because claim 1–5, 7, 9, 13–15, and 31 have been disclaimed, Petitioner’s
`
`asserted grounds of unpatentability as applied to those claims are now moot.
`
`The following grounds remain at issue in this proceeding:
`
`Claim(s) Challenged
`
`
`
`35 U.S.C. §
`
`Reference(s)/Basis
`
`6, 8, 10–12
`
`112(b)
`
`11, 12
`
`6, 8, 10–12
`
`102
`
`103
`
`Indefiniteness
`
`Shallal
`
`’529 publication
`
`6, 8, 10–12
`
`112(a)
`
`Enablement
`
`Patent Owner has chosen to waive its response to Petitioner’s arguments and
`
`evidence concerning these grounds. Nevertheless, the burden of proof for
`
`each of the alleged grounds of unpatentability remains on Petitioner.
`
`35 U.S.C. § 326(e) (2018); see Dynamic Drinkware, LLC v. Nat’l Graphics,
`
`Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015).
`
`ANALYSIS
`
`A.
`
`Claim Construction
`
`In a post-grant review, the claims are construed “using the same claim
`
`construction standard that would be used to construe the claim in a civil
`
`action under 35 U.S.C. § 282(b).” 37 C.F.R. § 42.200(b)(2019). Therefore,
`
`we construe the challenged claims under the framework set forth in Phillips
`
`v. AWH Corp., 415 F.3d 1303, 1312–19 (Fed. Cir. 2005) (en banc). Under
`
`this framework, claim terms are given their ordinary and customary
`
`meaning, as would be understood by a person of ordinary skill in the art at
`
`10
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`the time of the invention, in light of the language of the claims, the
`
`specification, and the prosecution history of record. Id.
`
`1.
`
`Variable “p” (claims 1–15, 31)
`
`Petitioner asserts that the challenged claims are unpatentable under
`
`35 U.S.C. § 112(b) because the variable “p” as recited in claim 1 is
`
`indefinite. See Pet. 30–35. To the extent Petitioner’s argument raises a
`
`claim construction issue, we address that issue in our analysis of Petitioner’s
`
`indefiniteness ground.
`
`2.
`
`Remaining Claim Terms
`
`Petitioner does not seek a construction for any other term and
`
`contends that these “claim terms should be given their ordinary and
`
`customary meaning.” Pet. 28–29. We agree that it is unnecessary to
`
`expressly construe any of the remaining claim terms to resolve the asserted
`
`grounds of unpatentability. See Nidec Motor Corp. v. Zhongshan Broad
`
`Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (explaining that it is
`
`only necessary to “construe terms ‘that are in controversy, and only to the
`
`extent necessary to resolve the controversy’” (quoting Vivid Techs., Inc. v.
`
`Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999))).
`
`B.
`
`Level of Ordinary Skill in the Art
`
`Petitioner describes a person with ordinary skill in the art as having “a
`
`Ph.D. degree and training in organic chemistry, medicinal chemistry,
`
`radiopharmaceutical chemistry, or a related field with at least two years of
`
`post-doctoral experience.” Pet. 18–19.
`
`Petitioner’s description of the level of ordinary skill in the art is
`
`sufficiently supported by the record. Moreover, we note that the applied
`
`prior art reflects the appropriate level of skill at the time of the claimed
`
`invention, which is consistent with Petitioner’s description. See Okajima v.
`
`11
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001). Thus, we adopt
`
`Petitioner’s description of a person of ordinary skill.
`
`C.
`
`Indefiniteness (claims 6, 8, and 10–12)
`
`Petitioner asserts that claims 6, 8, and 10–12 are indefinite because
`
`“[v]ariable p . . . appears at multiple locations on compounds of formula
`
`(II)” as recited in independent claim 1 and it is unclear whether: (1) “p is the
`
`same at each instance it appears in formula (II),” or (2) “p is independently
`
`selected each time it appears in formula (II).” Pet. 31. Petitioner urges that
`
`it “is not evident from the face of the claims” which of these two
`
`interpretations applies and that nothing in the intrinsic record of the ’974
`
`patent “resolve[s] the ambiguity in the claim language.” Id. at 33. Thus,
`
`Petitioner argues claims 6, 8, and 10–12 by virtue of their dependency of
`
`claim 1 are indefinite under both the “reasonable certainty” standard set
`
`forth in Nautilus Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 901 (2014),
`
`and the “amenable to two or more plausible claim constructions” analysis
`
`employed in Ex parte Miyazaki, 89 USPQ 2d 1207, 1211 (BPAI 2008)
`
`(precedential). Id.
`
`We are not persuaded that the variable “p” in claim 1 is reasonably
`
`susceptible to Petitioner’s second interpretation. Phillips makes clear that
`
`the surrounding claim language should be considered in determining the
`
`proper construction of a claim term. See Phillips, 415 F.3d at 1314. Here,
`
`both the context provided by the surrounding claim language and well-
`
`established claim construction principles support interpreting “p” to be the
`
`same integer each time it appears in the claim.
`
`Claim 1 recites express definitions for the variables in the recited
`
`formula. See Ex. 1001, 103:15–25. According to that claim language, “p is
`
`an integer selected from 0 to 10.” Id. But p is not the only variable given
`
`12
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`that definition. Claim 1 also defines “n,” “n1,” and “n2” as “an integer
`
`selected from 0 to 10.” Id. If p were “independently selected each time it
`
`appears,” according to Petitioner’s second interpretation, the same variable
`
`“p” could be used throughout the recited formula. Pet. 31. Thus, the fact
`
`that claim 1 recites four different variables (i.e., p, n, n1, and n2) with the
`
`same definition cuts against interpreting p to be independently selected each
`
`time it appears in the recited formula because such an interpretation would
`
`render the other identically-defined variables redundant. See, e.g., Akzo
`
`Nobel Coatings, Inc. v. Dow Chem. Co., 811 F.3d 1334, 1340 (Fed.
`
`Cir. 2016) (quoting Power Mosfet Techs., L.L.C. v. Siemens AG, 378 F3d
`
`1396, 1410 (Fed. Cir. 2004) (“Interpretations that render some portion of the
`
`claim language superfluous are disfavored.”).
`
`In addition, claim 1 defines other variables in the recited formula as
`
`follows: “wherein . . . X, Y, W, and Z represent independently of each
`
`other . . . .” Ex. 1001, 103:15–22 (emphasis added). The fact that claim 1
`
`expressly recites the term “independently” to define the selection of some of
`
`the variables in the recited formula, but not “p,” evidences that independent
`
`selection is not within the plain meaning of “p” and must be separately
`
`recited. See, e.g., Phillips, 415 F.3d at 1314 (explaining, by way of
`
`example, that the claim’s reference to “‘steel baffles’ . . . strongly implies
`
`that the term ‘baffles’ does not inherently mean objects made of steel.”).
`
`In addition, as a matter of general claim construction principles, there
`
`is a “presumption that the same terms appearing in different portions of the
`
`claims should be given the same meaning unless it is clear from the
`
`specification and prosecution history that the terms have different meanings
`
`at different portions of the claims.” Paragon Sol., LLC v. Timex Corp, 566
`
`F.3d 1075, 1087 (Fed. Cir. 2009) (quoting PODS, Inc. v. Porta Stor, Inc.,
`
`13
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`484 F.3d 1359, 1366 (Fed. Cir. 2007)). Petitioner’s first interpretation is
`
`consistent with this presumption because it interprets “p” to be the same
`
`integer at each instance of “p” in recited formula. On the other hand,
`
`Petitioner’s second interpretation runs contrary to the presumption because,
`
`as Petitioner points out, that interpretation allows “p” to have different
`
`meanings at each instance of “p” in the recited formula. See Pet. 32–33
`
`(giving an example where “p is 1 on the lysine-like moiety” and p is “6 on
`
`the linker”). Petitioner acknowledges that “nothing within the specification
`
`provides context” for selecting one interpretation over the other and Patent
`
`Owner “did not comment on the interpretation of p during prosecution.” Id.
`
`at 33. Thus, there is nothing in the Specification or prosecution history that
`
`provides the clear evidence typically necessary to depart from the
`
`presumption that “p” has the same meaning each time it appears in Patent
`
`Owner’s claims. Moreover, as explained above, the surrounding claim
`
`language affirmatively supports that “p” should be construed to be the same
`
`integer throughout claim 1.
`
`For these reasons, we construe “p” to be limited to the same integer
`
`selected from 0 to 10 at each instance within the formula recited in claim 1
`
`(and by dependency claims 6, 8, and 10–12). We do not agree that variable
`
`“p” is reasonably amenable to Petitioner’s second interpretation. Thus, we
`
`do not agree with Petitioner that claims 6, 8, and 10–12 are indefinite
`
`according to the analysis in Miyazaki. For similar reasons, we also are
`
`unmoved by Petitioner’s argument that these claims fail to meet the
`
`“reasonable certainty” standard in Nautilus. Accordingly, we determine
`
`Petitioner has failed to show that claims 6, 8, and 10–12 are indefinite by a
`
`preponderance of the evidence.
`
`14
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`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`D.
`
`Anticipation by Shallal (claims 11 and 12)
`
`Petitioner contends that Shallal was published on January 11, 2014,
`
`and is, therefore, prior art to the ’974 patent under 35 U.S.C. § 102(a)(1).
`
`Pet. 13–14. Petitioner asserts that claims 11 and 12 are anticipated by the
`
`disclosure of the compound “EUKL-NH2” in Shallal. See id. 45–54.
`
`Shallal discloses the synthesis of a “PSMA Targeting Agent” in the
`
`synthetic pathway shown in scheme 1. Ex. 1005, 397. EUKL-NH2 is
`
`disclosed as an intermediate in that pathway with the chemical structure
`
`shown below.
`
`
`
`Id.; see also id. at 394 (explaining that EUKL-NH2 “was obtained from the
`
`corresponding protected NHS ester 1”).
`
`Claims 11 and 12 depend from claim 1 and further limit “q” to an
`
`integer selected from “1 to 10” and “1 to 3” respectively. Ex. 1001, 108:50–
`
`54. Petitioner contends EUKL-NH2 discloses these limitations because it
`
`corresponds to the formula recited in claim 1, wherein E has the structure
`
`shown below. Pet. 47–48.
`
`According to Petitioner, EUKL-NH2 is structurally identical to the formula
`
`recited in claim 1 where the p in the formula (II) backbone is 1, the p in the
`
`E group above is 6, and q is 3. Id. at 48.
`
`
`
`15
`
`

`

`PGR2019-00052
`Patent 10,112,974 B2
`
`
`
`We do not agree with Petitioner. Petitioner’s argument relies upon an
`
`interpretation of the variable “p” that allows “p” to be independently
`
`selected each time it appears in the recited formula. As explained in our
`
`analysis of the indefiniteness ground, Petitioner’s interpretation is not
`
`supported by the intrinsic record and runs contrary to established claim
`
`construction principles. Instead, we construe “p” such that it must be the
`
`same integer throughout the recited formula.
`
`
`
`Under that construction EUKL-NH2 does not anticipate claims 11 and
`
`12 because EUKL-NH2 does not disclose the recited composition wherein
`
`the “p” in the formula (II) backbone and the “p” in the selected E group are
`
`the same integer. Accordingly, Petitioner has not shown by a preponderance
`
`of the evidence that claims 11 and 12 are anticipated by Shallal.6
`
`E. Obvious over the ’529 Publication (claims 6, 8, 10–12)
`
`Petitioner contends that the ’529 publication, which was published on
`
`December 31, 2008, is prior art to the ’974 patent under 35 U.S.C.
`
`§ 102(a)(1). Pet. 14. Petitioner asserts that claims 6, 8, and 10–12 would
`
`have been obvious over the ’529 publication. See Id. at 59–77.
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`Petitioner’s obviousness theory for claims 6 and 10–12 is premised on
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`the ’529 publication’s disclosure of compound L4. Id. The structure of
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`compound L4, as depicted in the Petition, is shown below.
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`
`
`6 The only ground of unpatentability that Petitioner advances based on
`Shallal is anticipation under 35 U.S.C. § 102. See Pet. 45–51. We have not
`been asked to consider whether any of the claims of the ’974 patent would
`have been obvious over EUKL-NH2 or any other teaching in Shallal.
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`Id. at 62. According to Petitioner, such conjugates have a “modular Block
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`A- Block B-Block C structure comprising a “GUL [Block A]” shown in red
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`in the figure above, “a linker [Block B]” shown in blue, and a
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`“radiolabel/chelator [Block C]” shown in pink. Id. at 61. Using Petitioner’s
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`terminology, compounds of formula (II) of the ’974 patent are Block A-
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`
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`Block B intermediates.
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`
`
`Petitioner acknowledges that “the ’529 publication discloses
`
`producing L4 by coupling the GUL (Block A) to a linker-chelator
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`intermediate (Block B-Block C).” Id. at 63 (citing Ex. 1006, 33 (scheme 2)).
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`Thus, the ’529 publication does not teach the synthesis of L4 through a
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`pathway involving a Block A-Block B intermediate like that in formula (II).
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`But according to Petitioner, “a person of ordinary skill in the art would have
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`recognized that L4 could also be prepared, e.g., using a GUL-linker
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`intermediate (Block A-Block B).” Id. Petitioner contends this “example
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`intermediate” would comprise a GUL moiety wherein the nitrogen in the
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`lysine amine forms an amide with the carbonyl of a linker group composed
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`of a six carbon alkyl chain joined by a secondary amide to another six
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`carbon alkyl chain terminating in a primary amine as shown in the structure
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`below (reproduced from the Petition).
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`PGR2019-00052
`Patent 10,112,974 B2
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`Id. According to Petitioner this “example intermediate” of L4 is similar to
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`the formula of claims 6 and 10–12, where the linker group E is one of the
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`two structures shown below and, therefore, has a structure similar to that
`
`described above. See id. at 68–69, 75–77.
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`
`
`
`
`
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`Claims 6 and 10–12 differ from Petitioner’s “example intermediate” of L4
`
`with respect to the length of the linker group adjacent to the terminal amine.
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`Petitioner asserts that it would have been obvious to modify the linker of this
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`“example intermediate” by changing the number of carbons in the linker to
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`arrive at the compounds in claims 6 and 10–12 because the linkers in those
`
`claims are all within the “range of lysine-linker lengths taught by the ’529
`
`publication (i.e., of between 7.7 and 33 Å).” Id. at 68 (citing Ex. 1006,
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`31:11–16, 38:29–39:2).
`
`We do not agree with Petitioner’s argument that claims 6 and 10–12
`
`would have been obvious over the ’529 publication. A patent claim is
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`unpatentable under 35 U.S.C. § 103 if the differences between the claimed
`
`subject matter and the prior art are such that the subject matter, as a whole,
`
`“would have been obvious at the time the invention was made to a person
`
`having ordinary skill in the art to which said subject matter pertains.” KSR
`
`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). Here, there are two
`
`modifications that would have had to be made to teachings in the ’529
`
`publications teachings to arrive at a compound within the scope of claims 6
`
`and 10–12. First, one of skill in the art would have had to use a different
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`synthetic scheme than the one taught in the ’529 publication so as to arrive
`
`at Petitioner’s “example intermediate of L4.” Second, one would have
`
`needed to vary the length of the linker so that the variables “m,” “n,” “p,”
`
`and “q” in the E group were within the range of integers recited in those
`
`claims.
`
`Regarding the first difference, Petitioner has not explained sufficiently
`
`why one of ordinary skill in the art would have been motivated to depart
`
`from the synthetic scheme taught in the ’529 publication and instead adopt a
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`different scheme involving the preparation of Petitioner’s “example
`
`intermediate.” Petitioner relies on the testimony of its expert, Dr. Stephen
`
`G. DiMagno, that “[d]espite the fact that the ’529 publication reports
`
`preparing L4 by coupling GUL (Block A) to a linker-chelator intermediate
`
`(Block B-Block C), a person of ordinary skill in the art would also recognize
`
`that L4 could easily be prepared using” a Block A-Block B intermediate,
`
`i.e., the “Example Intermediate of L4.” Ex. 1002 ¶ 70. But evidence that L4
`
`could have been prepared according to an alternative pathway involving
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`Petitioner’s “example intermediate” does not demonstrate that it would have
`
`been obvious to make such a modification to the teachings in the ’529
`
`publication. “In cases involving new chemical compounds, it remains
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`necessary to identify some reason that would have led a chemist to modify a
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`known compound in a particular manner to establish prima facie
`
`obviousness of a new claimed compound.” Sanofi-Aventis U.S., LLC v. Dr.
`
`Reddy’s Labs., Inc., 933 F.3d 1367, 1375 (Fed. Cir. 2019) (quoting Takeda
`
`Chem. Indus. Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir.
`
`2007)). Here, neither Petitioner, nor its expert, have sufficiently identified a
`
`reason why one of skill in the art would have modified the synthetic pathway
`
`taught for making L4 in the ’529 publication (i.e., scheme 2) so as to arrive
`
`at Petitioner’s “example intermediate.”
`
`We also do not agree with Petitioner’s reliance on scheme 7 of the
`
`’529 publication. The ’529 publication teaches that scheme 7 (reproduced
`
`below) is the synthetic pathway used for “Synthesis of DOTA analogs.”
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`
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`Ex. 1006, 35–36. According to Petitioner, scheme 7 depicts a reaction
`
`involving the coupling of a Block A-Block B intermediate (16, 17) to a
`
`Block C chelator. See Pet. 61–62. But again, the Petition fails to identify a
`
`reason why one of skill in the art would have modified the teachings in the
`
`’529 publication so as to use such a reaction to make L4. Indeed, the ’529
`
`publication teaches the pathway and intermediates shown in scheme 7 to
`
`make “DOTA analogs,” not L4. Ex. 1006, 35. The synthesis of L4 is
`
`described in a separate section of the ’529 publication titled “Synthesis of
`
`Urea-linked Chelators” that describes the synthesis of compounds L1–L7
`
`according to different synthetic schemes. Id. at 31–33. Petitioner has not
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`identified anything in the ’529 publication that suggests scheme 7 should be
`
`used to make L4 or any other non-DOTA compound.
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`For these reasons, Petitioner has not shown its “example intermediate
`
`of L4” would have been an obvious modification of the teachings in the ’529
`
`publication. Since Petitioner’s obviousness argument for claims 6 and 10–
`
`12 is premised on first modifying the synthetic pathway taught in the ’529
`
`publication so as to make this “example intermediate” before making further
`
`modifications to change the length of the linker, Petitioner has not shown by
`
`a preponderance of the evidence that the compositions recited in claims 6
`
`and 10–12 would have been obvious over the ’529 publication.
`
`
`
`Petitioner’s obviousness theory for claim 8 is similar to that for the
`
`other claims, but premised upon an “example intermediate” for a different
`
`compound, i.e., compound L7, of the ’529 publication. See Pet. 74–75. The
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`’529 publication teaches that L7 is prepared according to the same reaction
`
`scheme as L4. Ex. 1006, 33 (scheme 2). This scheme does not involve
`
`formation of a Block A-Block B intermediate like that in formula (II) of the
`
`’974 patent. Accordingly, Petitioner’s obviousness argument for claim 8 is
`
`likewise premised on modifying the synthetic pathway taught in the prior art
`
`to produce an “example intermediate” that is not explicitly taught in the ’529
`
`publication. As explained above, Petitioner has not sufficiently identified a
`
`reason why one of skill in the art would have been motivated to make such a
`
`modification. Thus, we determine Petitioner has not shown by a
`
`preponderance of the evidence that claim 8 would have been obvious over
`
`the ’529 publication.
`
`F.
`
`Enablement (claims 6, 8, and 10–12)
`
`Petitioner asserts that claims 6, 8, and 10–12 are unpatentable for lack
`
`of enablement under 35 U.S.C. § 112(a). See Pet. 84–93 (analyzing factors
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`articulated in In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988)). Petitioner
`
`argues that the Specification exemplifies preparation of “only 5 compounds
`
`of formula (II) (compounds 2b, 2d, 2k, 2p, and 2n).” Id. at 88. Thus,
`
`according to Petitioner, many of the “E values” recited in claim 1 (and by
`
`dependency claims 6, 8, and 10–12) are not exemplified, nor does the
`
`Specification otherwise “provide the requisite description of how to prepare
`
`the full scope of the claimed linker moieties.” Id. at 89–92. In sum,
`
`Petitioner argues,
`
`because the ’974 patent fails to provide any illustration as to
`how to prepare the claimed compounds, including the recited
`linker moieties highlighted above (i.e., benzyl-substituted linker
`moieties), and because there is no known correlation between
`these compounds and the exemplified compounds, claims 1–12,
`14, and 15 (i.e., claims related to formula (II) that encompass
`these E values) are unpatentable for lack of enablement.
`
`Id. at 93.
`
`
`
`We do not agree with Petitioner’s lack of enablement argument. As
`
`Petitioner acknowledges, the Specification provides working examples for a
`
`number of the recited E groups and teaches a general method “using urea-
`
`glutamate based compounds . . . as building blocks” to make such
`
`compounds. See Id. at 88–91 (citing Ex. 1001, 21:3–21 and Examples 13–
`
`18). Petitioner has not, however, presented persuasive evidence or argument
`
`to explain why one of ordinary skill in the art could not or would not readily
`
`adapt these techniques to make compounds embodying the full scope of
`
`recited E groups.
`
`The Specification provides a number of teachings regarding the
`
`synthesis of formula (II) compounds that are not addressed in Petitioner’s
`
`enablement analysis. For example, the Specification explains, “[t]ypically,
`
`the synthesis of the compounds is started by the preparation of urea
`
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`pharmacophore units . . . as described by Maresca et al. (J. Med. Chem.,
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`2009, 52 (2), pp 347–357).” Ex. 1001, 20:66–21:3. But the Petition does
`
`not address whether such prior art synthetic techniques could be used to
`
`make the claimed compounds. Moreover, the Specification teaches that
`
`formula (II) compounds “may be readily prepared by reactions between
`
`amines and activated carboxylic acids or active esters” and provides specific
`
`examples of reagents for these techniques. See id. at 21:4–13. In addition,
`
`the Specification teaches that “protecting groups” may be used to allow
`
`“amines, carboxylic acids, and amino acids” to be used as “building blocks”
`
`to make such compounds. Id. at 21:15–21.
`
`Petitioner does not sufficiently account for these teachings in its
`
`Wands factor analysis. See Pet. 88–92. For instance, the Specification states
`
`that “amino acids” can be used as “building blocks” for formula (II)
`
`compounds and cites Examples 15–18 as ev