`Tel: 571-272-7822
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`Paper 52
`Entered: March 26, 2020
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`GRÜNENTHAL GMBH,
`Petitioner,
`
`v.
`
`ANTECIP BIOVENTURES II LLC,
`Patent Owner.
`____________
`
`Case PGR2018-00001
`Patent 9,539,268 B2
`____________
`
`
`
`Before TONI S. SCHEINER, GRACE KARAFFA OBERMANN, and
`SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`OBERMANN, Administrative Patent Judge.
`
`
`REHEARING DECISION
`Denying Patent Owner’s Request for Rehearing
`37 C.F.R. § 42.71(d)
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`PGR2018-00001
`Patent 9,539,268 B2
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`I. INTRODUCTION
`Patent Owner filed a Request for Rehearing (Paper 49, “Req. Reh’g”)
`seeking review of the Board’s Final Written Decision (Paper 48, “Dec.”), in
`which we held unpatentable claims 3–30 of U.S. Patent No. 9,539,268 B2
`(Ex. 1001, “the ’268 Patent”). With Board pre-authorization (Paper 50),
`Petitioner filed a Response to the Request for Rehearing. Paper 51 (“Reh’g
`Resp.”). This Decision also refers to the Petition (Paper 2, “Pet.”), the Patent
`Owner’s Response (Paper 22, “Resp.”), Petitioner’s Reply (Paper 36,
`“Reply”), and Patent Owner’s Sur-Reply (Paper 39, “Sur-Reply”).
` Upon request for rehearing, we review our decision for an abuse of
`discretion. 37 C.F.R. § 42.71(c). “The burden of showing a decision should
`be modified lies with the party challenging the decision.” 37 C.F.R.
`§ 42.71(d). “The request must specifically identify all matters the party
`believes the Board misapprehended or overlooked, and the place where each
`matter was previously addressed in a motion, an opposition, or a reply.” Id.
`Based on an application of those principles, we deny the Request for
`Rehearing.
`
`II. DISCUSSION
`The claimed invention relates to unenhanced dosage forms of
`zolendronic acid that achieve a bioavailability in humans “from about 1.1%
`to about 4%.” Dec. 6 (quoting claim 1). In a nutshell, we found that the
`written description of the ’268 Patent lacks guideposts sufficient to enable an
`ordinarily skilled artisan to practice the claimed invention, because the
`description does not explain how to differentiate dosage forms that achieve
`the required bioavailability from those that do not. Id. at 12–21.
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`Patent Owner requests modification of the Final Written Decision on
`four grounds. First, Patent Owner submits, the Board misattributed a
`statement made by Petitioner’s witness to Patent Owner’s witness. Req.
`Reh’g 2–3. Second, Patent Owner contends that the Board overlooked or
`misapprehended information bearing on the issue of enablement. Id. at 3–11.
`Third, Patent Owner argues that the Board overlooked or misapprehended an
`alleged admission by Petitioner that an ordinarily skilled artisan “could
`achieve a bioavailability above 1% for zoledronic acid without using a
`bioavailability enhancing agent.” Id. at 12. Fourth, Patent Owner argues that
`the Board misapplied or misunderstood principles governing the evidentiary
`showing applicable to enablement. Id. at 13. We address in turn each of
`those asserted grounds for modification.
`
`A. Alleged Misattribution of Testimonial Evidence
`We agree with Patent Owner that, in one instance, the Board
`misattributed testimony of Petitioner’s witness, Dr. Clive G. Wilson, to
`Patent Owner’s witness, Dr. William Wargin. Req. Reh’g 2 (citing Dec. 14).
`That circumstance does not persuade us of reversible error, however, or
`otherwise compel modification of the Final Written Decision.
`Dr. Wilson, not Dr. Wargin, likened the belief that unenhanced
`zolendronic acid dosage forms could achieve bioavailabilities as high
`as 1.1% to “a belie[f] in ‘fairies.’” Req. Reh’g 2 (quoting Dec. 14; Ex. 2014,
`137:21–138:8). That testimony represents a small fraction of the totality of
`evidence that undergirds our finding that an ordinarily skilled artisan
`generally would have expected that attaining a human bioavailability for
`zolendronic acid above 1% required an enhancer. See Dec. 12–21 (citing
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`Patent 9,539,268 B2
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`substantial evidence for that proposition). Even if we set aside the testimony
`misattributed to Dr. Wargin, substantial evidence supports that finding.
`Patent Owner unequivocally admitted as much, stating that an
`ordinarily skilled artisan at the time of the invention would have “believed
`that the oral bioavailability in humans of all forms for zoledronic acid could
`not be above 1% without an enhancer.” Resp. 1 (emphasis in original). That
`admission is consistent with other persuasive evidence on point, including
`the Specification of the ’268 Patent, which indicates that the bioavailability
`of unenhanced zolendronic acid forms is low, with some forms having a
`bioavailability as low as 0.01%. Dec. 13 (citing Ex. 1001, 13:57‒59), 14
`(citing Ex. 1001, 14:8–11).
`The Final Written Decision turns on the lack of guideposts in the
`Specification (for example, the absence of any pharmacokinetic data or
`disclosure of even one example of a dosage form that meets the challenged
`claims). Id. at 13–14 (citing Ex. 1005 ¶¶ 64–65, 69). The lack of a working
`example, however, is just one fact contributing to the totality of
`circumstances that support our holding of non-enablement. At its core, this
`case turns on the lack of disclosure in the Specification combined with the
`unpredictable nature of the field of invention of pharmaceutical formulation.
`Id. at 12. Substantial evidence of record points in one direction; that an
`ordinarily skilled artisan generally would have expected unenhanced
`zoledronic acid dosage forms to exhibit a bioavailability in humans of 1% or
`lower. Id. at 12–13. Neither the Specification, nor any general understanding
`in the art, would have equipped an ordinarily skilled artisan to distinguish
`unenhanced dosage forms that achieve the bioavailability required by the
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`challenged claims from those that do not, absent undue experimentation. Id.
`at 13–21.
`Alternatively, the testimony at issue carries some weight even when
`properly attributed to Dr. Wilson. Significantly, on that point, Dr. Wargin’s
`testimony aligns with Dr. Wilson’s testimony. Dr. Wargin similarly testifies
`that an ordinarily skilled artisan “would not have expected that the oral
`bioavailability of zolendronic acid could be above 1% in human beings
`without using an enhancer.” Reh’g Resp. 1–2 (quoting Ex. 2017 ¶ 98). The
`witnesses, in essence, agree on the underlying technical fact at hand. Patent
`Owner does not show reversible error based on the isolated instance in
`which the Board misattributed Dr. Wilson’s testimony to Dr. Wargin.
`In sum, substantial evidence supports our determination that the
`disclosure of the ’268 Patent lacks guideposts sufficient to illuminate a path
`toward unenhanced dosage forms that fall within the scope of the challenged
`claims. See Dec. 15–20 (citing evidence on point). Accordingly, as
`Petitioner points out, the misattribution of testimony was inconsequential.
`Sur-Reply 1 (heading).
`
`B. Alleged Failure to Comprehend Evidence of Enablement
`Patent Owner asserts that the Board, in four instances, reversibly erred
`by overlooking or misapprehending arguments and evidence pertaining to
`enablement. Req. Reh’g 3–4. All four instances generally relate to our
`finding that an ordinarily skilled artisan would have expected unenhanced
`zoledronic acid “to have an oral bioavailability of less than 1%” and that
`the ’268 Patent lacks guidance sufficient to explain how to identify
`unenhanced dosage forms that meet the claim limitation requiring a
`bioavailability in humans from about 1.1% to about 4%. Req. Reh’g 3
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`(citing Dec. 17–18); see Ex. 1001, claims 1 and 3 (independent claim
`specifying that bioavailability range); see also id. at claim 23 (independent
`claim specifying an unenhanced dosage form of zolendronic acid that
`exhibits a human bioavailability from “about 1.2% to about 4%”).
`First, Patent Owner directs us to testimony of Dr. Wargin pertaining
`to “a human clinical trial using a dosage form” of zolendronic acid that
`included “no bioavailability enhancing agents,” but nonetheless achieved “a
`bioavailability occupying a significant portion of the” ranges required by the
`challenged claims. Req. Reh’g 4 (citing Ex. 2017 ¶¶ 54–78 (discussing
`Ex. 2026)). That evidence is an undated, four-page summary document
`bearing the legend “CONFIDENTIAL.” Ex. 2026. Patent Owner first
`introduced that evidence in the Response in connection with a dosage form
`denoted as “AZS-02.” Resp. 23 (citing Ex. 2026); see id. at 1, 8, 10 (for
`additional argument pertaining to that undated summary document).
`Patent Owner made no showing in the Response (or any other brief of
`record) that Exhibit 2026 would have been publicly accessible or otherwise
`available to inform the understanding of an ordinarily skilled artisan at the
`time of the invention. See generally Resp.; see also Reply 8–10 (Petitioner,
`explaining that the data in Exhibit 2026, which Patent Owner advances in
`the Response to establish the bioavailability achieved in Aronhime
`(Ex. 1035), was not available at the time of filing of the Petition).
`After Patent Owner filed Exhibit 2026 in support of the Response, the
`parties argued at some length about its evidentiary impact. See, e.g.,
`Reply 8–10; Sur-Reply 4–6. Petitioner asserted that, if Dr. Wargin is correct
`that the summary document (Ex. 2026) demonstrates that an unenhanced
`dosage form of zolendronic acid disclosed in another document (identified
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`by the parties as Aronhime (Ex. 1035)) inherently meets the bioavailability
`range required by the challenged claims, then Aronhime (Ex. 1035)
`represents an anticipatory reference. Reply 8–11. Relevant to enablement,
`however, Patent Owner nowhere asserted, much less established, that an
`ordinarily skilled artisan would have been privy to the summary results
`(Ex. 2026) or otherwise would have been aware of the bioavailability
`achieved by Aronhime (Ex. 1035). Sur-Reply 5 (referring to an unenhanced
`dosage form of zoledronic disodium tetrahydrate that could achieve with
`“95% confidence” a bioavailability of up to “3.06%” (as disclosed in Exhibit
`2026) but arguing that “Aronhime does not expressly disclose an oral dosage
`form containing” the same “excipients” as the form discussed in Exhibit
`2026 “and there is no way of knowing that an oral dosage form containing
`other excipients would have the same bioavailability”).
`In any event, the critical question is not whether one particular
`unenhanced dosage form of zoledronic acid disclosed in Aronhime or
`Exhibit 2026 would have attained a bioavailability that falls within the scope
`of the challenged claims. The key is whether an ordinarily skilled artisan,
`reading the disclosure of the ’268 Patent, would have been equipped to
`practice the full scope of the claimed invention. We did not overlook or
`misapprehend Exhibit 2026. We correctly determined that, in this
`unpredictable field of pharmaceutical formulation, an ordinarily skilled
`artisan would have required direction (lacking in the Specification or the
`prior art) explaining how to prepare dosage forms that meet the full range of
`bioavailabilities embraced by the challenged claims, including the specified
`high endpoint human bioavailability of about 4%. See, e.g., Dec. 11–12
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`(citing undisputed evidence of unpredictable nature of the field of invention
`(Ex. 1005 ¶ 60)).
`Significantly, on that point, Dr. Wargin states he was privy to
`information regarding Exhibit 2026 as part of this proceeding but does not
`suggest that this information would have been publicly available at the time
`of the invention. See, e.g., Ex. 2017 ¶ 54 (Dr. Wargin’s testimony that his
`opinions were formed based on information, which was made available to
`him in connection with this proceeding, including “access to individuals”
`having personal knowledge of the clinical trial). Exhibit 2026 includes, on
`every page, a notation that the document was, at least at some point, treated
`as confidential. Ex. 2026 (summary of results from the clinical trial, marked
`on every page as “CONFIDENTIAL”). Patent Owner directs us to no
`persuasive evidence that an ordinarily skilled artisan, seeking to practice the
`claimed invention, could or would have turned to the summary document of
`the clinical trial (Ex. 2026) for direction at the time of the invention.
`Alternatively, even if we accept that the summary document
`(Exhibit 2026) would have been publicly accessible at the time of the
`invention, Patent Owner directs us to no persuasive evidence that the
`document enables the full scope of the challenged claims. Exhibit 2026
`discloses a dosage form that may have exhibited a bioavailability
`of “3.06%” – which falls well short of the 4% endpoint specified in the
`challenged claims. Ex. 2026, 2. Patent Owner does not explain how or why
`an ordinarily skilled artisan, privy to that result, would have been equipped
`to prepare an unenhanced dosage form with a reasonable expectation of
`attaining a bioavailability in humans of “about 4%” –– that is, the high
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`endpoint of the specified bioavailability ranges. Ex. 1001, claims 1, 3,
`and 23; Req. Reh’g 4.
`Multiple variables, including the form of the active ingredient, its
`degree of solubility, and the process by which it is manufactured, would
`have been understood to “have unpredictable effects on bioavailability.’”
`Dec. 12. Given that unpredictability, we correctly found the Specification
`lacking in disclosure sufficient to guide one to dosage forms that attain the
`full range of human bioavailabilities specified in the challenged claims
`(including the high endpoint of 4%). A preponderance of evidence supports
`our finding that the identification of workable dosage forms would have
`required more than an exercise of ordinary skill in this particular field of
`endeavor. Id. at 11–20 (including citations to evidence that the ’268 Patent
`lacks sufficient guidance in view of the unpredictable nature of the technical
`field of the invention).
`Second, Patent Owner avers that the Board erroneously held “that
`unenhanced zoledronic acid in oral dosage forms cannot have a
`bioavailability over 1%.” Req. Reh’g 5. On the contrary, we held that the
`Specification lacks information that “would have guided the artisan to a
`selection of zolendronic acid dosage forms” that meet “the full range of
`claimed bioavailabilities.” Dec. 13. On that point, even Patent Owner
`acknowledges, “an ordinarily skilled artisan would have ‘believed that the
`oral bioavailability in humans of all forms for zolendronic acid could not be
`above 1% without an enhancer.’” Id. at 13 (quoting Resp. 1). Even if, as
`Patent Owner now asserts, that artisan would have expected some
`unenhanced dosage forms to exhibit a bioavailability above 1%, no showing
`is made that one would have understood how to formulate a dosage form
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`that achieves the high endpoint of human bioavailability (of about 4%)
`encompassed by the challenged claims.
`Petitioner did not argue, and the Board did not find, “that all
`unenhanced zoledronic acid dosage forms had a bioavailability of less
`than 1%, nor did Petitioner claim that the prior art asserted that
`bioavailabilities greater than 1% were impossible to achieve with zoledronic
`acid in the absence of an enhancer.” Reh’g Resp. 3. The crucial distinction is
`that, at the time of the invention, “[t]he prior art would have suggested” the
`difficulty of identifying, without guidance, dosage forms of unenhanced
`zoledronic acid that attain a bioavailability of 1% or more in humans. Id.
`at 3–4 (citing Pet. 20) (emphasis in original). Although the claims broadly
`embrace unenhanced dosage forms that attain a bioavailability in humans of
`up to about 4%, neither the written description nor the prior art of record
`explains how to identify those dosage forms.
`Patent Owner contends that the Board erroneously credited “four
`sources” of evidence advanced by Petitioner to demonstrate that unenhanced
`forms of zolendronic acid would have been understood at the time of the
`invention to have an oral bioavailability of less than 1%. Id. at 4–5. That
`assertion relates to Patent Owner’s erroneous assumption that the Decision
`rests on a finding that no unenhanced oral dosage forms of zoledronic acid
`could, in fact, exhibit a bioavailability over 1%. Id. The rationale that
`undergirds our Decision, however, is that distinguishing dosage forms that
`fall within the scope of the claims, from those that do not, would have
`required more than an exercise of ordinary skill in the art; such an endeavor
`would have required undue experimentation. Dec. 12–20.
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`Third, according to Patent Owner, the Board failed to comprehend
`evidence that the ’268 Patent does, in fact, provide guidance adequate “to
`prepare a dosage form having a bioavailability” that falls within the
`challenged claims. Req. Reh’g 7. Here again, however, the relevant question
`is not whether the disclosure provides guidance sufficient to practice a single
`embodiment of the invention. The question is whether the disclosure enables
`the full scope of the challenged claims. As we stated in the Decision, the
`Specification includes no “instructions or guidance as to how to achieve the
`recited range” of human bioavailability “without the use of enhancers.”
`Reh’g Resp. 7 (citing Dec. 16). “Even if,” as Patent Owner submits, the ’268
`Patent discloses “one embodiment of the claims, this is insufficient to”
`establish enablement with respect “to the full scope of the claims,” including
`the high endpoint human bioavailability of about 4%. Id. (footnote omitted).
`Fourth, Patent Owner submits, “clinical trials are routine
`experimentation and therefore not undue experimentation”—a position
`allegedly overlooked or misapprehended by the Board. Req. Reh’g 9. Patent
`Owner argues that both parties’ witnesses described as routine
`experimentation “the one year of work and one million dollars” that would
`have been required to demonstrate that even one dosage form exhibits the
`human bioavailability required by the challenged claims. Id. at 11. Patent
`Owner reargues that issue without identifying with any particularity
`reversible error in our reasoning. Id. Simple disagreement with the result
`does not show reversible error in our rationale. See Dec. 15–20 (including
`citations to substantial evidence undercutting Patent Owner’s view that the
`identification of workable dosage forms would have required no more than
`an exercise of ordinary skill in the art). Further, as Petitioner points out, this
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`is not a case in which the patent disclosure “gives instructions as to how to
`vary the parameters of interest.” Reh’g Resp. 7. “The fact that clinical trials
`might be considered ‘routine’ experimentation in certain circumstances
`misses the point.” Id. at 6. Here, given the broad range of human
`bioavailabilities encompassed by the challenged claims (ranging from about
`1.1% up to about 4%), “it would require multiple, extensive clinical trials to
`enable the practice of the full scope of the claims.” Id. Under the
`circumstances, Patent Owner does not show reversible error.
`
`C. Alleged Failure to Comprehend Admission
`Patent Owner asserts that the Board overlooked or misapprehended
`“the fact that Petitioner admitted that a” person of ordinary skill in the art
`“could achieve a bioavailability above 1% for zoledronic acid without using
`a bioavailability enhancing agent.” Req. Reh’g 12 (emphasis omitted). For
`support, Patent Owner directs us to a statement from Petitioner’s Reply:
`“Patent Owner does not explain why a bioavailability of 1.59-2.08% for a
`disodium salt form of zoledronate is unexpected in light of higher reported
`bioavailabilities for other similar bisphosphonates.” Id. (quoting Reply 16).
`In Patent Owner’s view, that statement amounts to an admission “that a
`bioavailability over 1% for a disodium salt form of zolendronic acid is not
`unexpected–that it is indeed expected.” Id. (emphasis omitted).
`Patent Owner contends that the Board’s failure to address that alleged
`“admission” regarding unexpected results amounts to reversible error. Id.
`Petitioner counters that the Board did not need to address the alleged
`admission regarding unexpected results, “because the Board declined to
`reach Petitioner’s obviousness grounds” implicating such results. Reh’g
`Resp. 9. Petitioner’s argument, however, misses the mark because that
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`alleged admission does represent an element of extrinsic evidence
`suggesting that attaining a dosage form that falls within the claimed
`bioavailability ranges would have been within the grasp of the ordinarily
`skilled artisan.
`That modicum of extrinsic evidence, however, does not compel a
`modification of the Final Written Decision. The alleged admission is offset
`by other extrinsic evidence; namely, testimony of Patent Owner’s own
`witness, unequivocally asserting that an ordinarily skilled artisan “would not
`have expected that the oral bioavailability of zoledronic acid could be above
`1% in human beings, without using an enhancer.” Id. at 8 (quoting Ex. 2017
`¶ 98). Here again, for reasons explained above, the critical question is
`whether it would have been within the level of ordinary skill in the art to
`practice, without undue experimentation, the full scope of the claims, a feat
`that requires identifying unenhanced dosage forms that exhibit the high
`endpoint of human bioavailability (about 4%) embraced by the challenged
`claims. On balance, the extrinsic evidence cited by Patent Owner does not
`improve the guidance in the Specification or otherwise establish that an
`ordinarily skilled artisan would have understood how to achieve an
`unenhanced dosage form of zolendronic acid characterized by a human
`bioavailability of “about 4%.” Ex. 1001, claims 1, 3, and 23; see Req.
`Reh’g 12 (citing Reply 16, which generally refers to bioavailabilities higher
`than 2.08% without directing us to persuasive intrinsic support).
`In sum, Patent Owner does not show that the asserted admission tips
`the totality of evidence towards a finding that an ordinarily skilled artisan
`would have been equipped to practice the full scope of the challenged claims
`without undue experimentation.
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`D. Alleged Failure to Apply Applicable Evidentiary Standards
`Patent Owner argues, “The fact that a [person of ordinary skill in the
`art] might not believe the disclosure” of the Specification (namely, that some
`dosage forms of unenhanced zolendronic acid are capable of achieving a
`human bioavailability as high as about 4%) “does not defeat enablement.”
`Req. Reh’g 13. In Patent Owner’s view, that circumstance indicates “expert
`skepticism” as a secondary indicium of nonobviousness. Req. Reh’g 13. The
`Board did not address any ground based on obviousness; therefore, Patent
`Owner’s assertion regarding alleged objective indicia of nonobviousness is
`misplaced. See Dec. 20 (conclusions on patentability of claims 3–30).
`Further, even if we accept Patent Owner’s view that the inventors
`recognized (and disclosed) that unenhanced forms of zolendronic acid
`(contrary to general belief) are capable of attaining the high endpoint
`bioavailability (of about 4% in humans), that circumstance does not end the
`inquiry. Req. Reh’g 13. The Board conducted an appropriate analysis
`grounded in the Wands factors1 to conclude that the Specification provides
`insufficient guidance to enable an ordinarily skilled artisan to identify “even
`one” unenhanced dosage form that meets the bioavailability requirements of
`the challenged patent claims – much less equip that artisan to attain the full
`range of human bioavailabilities specified in the challenged claims. Dec. 17.
`Accordingly, Patent Owner does not establish reversible error based on an
`alleged failure of the Board to apply the governing evidentiary standards
`applicable to enablement.
`
`
`1 In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988) (listing non-exclusive
`factors to assist in resolving the issue of enablement).
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`CONCLUSION
`III.
`For the above reasons, we deny Patent Owner’s Request for
`Rehearing of the Board’s Final Written Decision in this proceeding.
`
`V. ORDER
`
`It is
`ORDERED that Patent Owner’s Request for Rehearing of the Final
`Written Decision is denied.
`
`
`PETITIONER:
`
`Bruce C. Haas
`Stephen Yam
`VENABLE LLP
`GrunenthalPGR@Venable.com
`BCHaas@Venable.com
`SYam@Venable.com
`
`
`PATENT OWNER:
`
`Brent A. Johnson
`R. Parrish Freeman
`Michael I. Katz
`MASCHOFF BRENNAN
`bjohnson@mabr.com
`pfreeman@mabr.com
`mkatz@mabr.com
`
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