SALK INSTITUTE FOR BIOLOGICAL STUDIESDownload PDFPatent Trials and Appeals BoardMay 19, 202014783633 - (D) (P.T.A.B. May. 19, 2020) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/783,633 10/09/2015 Fred H. Gage 082700.0131 1031 21003 7590 05/19/2020 BAKER BOTTS L.L.P. 30 ROCKEFELLER PLAZA 44TH FLOOR NEW YORK, NY 10112-4498 EXAMINER CORDAS, EMILY ANN ART UNIT PAPER NUMBER 1632 NOTIFICATION DATE DELIVERY MODE 05/19/2020 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): DLNYDOCKET@BAKERBOTTS.COM PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE _________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD _________________ Ex parte FRED H. GAGE and CEDRIC BARDY _________________ Appeal 2019-005153 Application 14/783,633 Technology Center 1600 _________________ Before DEBORAH KATZ, JOHN G. NEW, and RYAN H. FLAX, Administrative Patent Judges. KATZ, Administrative Patent Judge. DECISION ON APPEAL Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the Examiner’s decision to reject claims 1–193. (Appeal Br. 1.) We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party-in-interest as Salk Institute for Biological Studies. (Appeal Br. 2.) 2 We consider the Final Office Action issued July 27, 2018 (“Final Act.”), the Appeal Brief filed February 28, 2019 (“Appeal Br.”), the Examiner’s Answer issued on April 24, 2019 (“Ans.”), the Reply Brief filed June 24, 2019 (“Reply Br.”) and the oral argument held on May 6, 2020, in reaching our decision. 3 Claims 20–24 have been withdrawn and claim 25 was canceled. (See Appeal Br. 19–20.) Appeal 2019-005153 Application 14/783,633 2 The Examiner rejected claims 1, 2, 5–16, 18, and 19 under 35 U.S.C. § 103 over Brewer4, Zeiger5, and Spiliotopoulos.6 (Ans. 4–8.) Appellant’s specification is directed to culture conditions for growing brain cells in vitro. (Spec. 1:20–25.) Appellants’ claim 1 recites: A cell medium comprising: (a) Sodium chloride at a concentration of between about 70 and about 150 mM; (b) a neuroactive inorganic salt at a concentration of between about 0.000001 and about l0mM; (c) Glycine at a concentration of between about 0.0001 and about 0.05 mM; (d) L-alanine at a concentration of between about 0.0001 and about 0.05 mM; and (e) L-serine at a concentration of between about 0.001 and about 0.03 mM; wherein (a) through (e) are each present at a concentration that maintains the survival and in vivo-like neurophysiological function of a neural cell cultured in the medium in vitro, wherein the in vivo-like neurophysiological function comprises synaptic function, action potential generation, energetic maintenance, or combinations thereof. (Appeal Br. 16.) We note that the claimed ranges are quite broad. For example Appellant’s claimed cell medium includes a neuroactive inorganic salt in a range of concentrations on the order of 107. 4 Brewer, U.S. Patent Application Publication 2008/0160006 A1, published July 3, 2008. 5 Zieger et al., “Assessing Neuronal Bioenergetic Status,” Methods in Mol. Bol., 758:215–35 (2011). 6 Spiliotopoulos et al., “An optimized experimental strategy for efficient conversion of embryonic stem (ES)-derived mouse neural stem (NS) cells into a nearly homogeneous mature neuronal population,” Neurobiology of Disease, 34:320–21 (2009). Appeal 2019-005153 Application 14/783,633 3 The Examiner finds that Brewer teaches a medium including the components recited in claim 1. (See Ans. 4, citing Brewer ¶ 28.) Although Brewer does not teach these components in exactly the same ranges recited in claim 1, as the Examiner finds, it teaches them in ranges significantly overlapping the recited concentrations. (See id.) The table below provides a comparison of the concentrations of components taught in Brewer with the concentrations recited in Appellant’s claim 1. Component Concentration7 in Brewer Table 1 Concentration in Claim 1 Sodium chloride 30.000-150.000 mM between about 70 and about 150 mM Potassium chloride (neuroactive inorganic salt) 2.500-10.000 mM between about 0.000001 and about 10 mM Glycine 0-2.400 mM between about 0.0001 and about 0.05 mM L-alanine 0-0.120 mM between about 0.0001 and about 0.05 mM L-serine 0-2.400 mM between about 0.001 and about 0.03 mM Brewer teaches a cell medium with the components of the claimed composition in ranges that significantly overlap those recited. The Examiner also finds that Brewer teaches the medium promotes the survival and regeneration of adult human neurons. (See Ans. 5, citing Brewer ¶ 32.) Brewer teaches further that cultures could be maintained in the medium for many weeks, long enough to demonstrate the appearance of 7 Concentrations converted to mM from the µM values provided in Brewer Table 1. Appeal 2019-005153 Application 14/783,633 4 synaptic elements, such as synaptic boutons, synaptic vesicles, and postsynaptic densities. (See id.) In addition, Brewer teaches that the culture medium maintains and improves viability of exposed, injured and isolated neural cells. (See Brewer ¶¶ 2, 12; see Ans. 5.) The Examiner finds that one of ordinary skill in the art would have recognized that all of the components of a culture medium are result- effective variables and that the concentration of the components of a cell medium would have been a matter of routine optimization, as evidenced by Brewer. (See Ans. 5–6.) Brewer teaches further that media can be formulated to optimize particular outcomes, such as improved survival of embryonic rat hippocampal neurons. (See Brewer ¶ 4; Ans. 5–6.) Appellant argues that the Examiner failed to establish a prima facie case for obviousness by allegedly conceding that two of the three functional properties recited in claim 1 are not disclosed in Brewer. (See Appeal Br. 6, 9.) Appellant also argues that the Examiner improperly shifted the burden to Appellant to establish the criticality of the ranges claimed and failed to show why it would have taken only routine optimization to arrive at the claimed ranges. (See id.) Appellant cites In re Stepan Co., 868 F.3d 1342, 1348 (Fed. Cir. 2017), in support of the these arguments. (See id.) We are not persuaded that the Examiner erred by ignoring the functional properties recited in claim 1. At the outset, we disagree that the Examiner conceded that the functional properties recited in claim 1 are not taught in Brewer. (Contra Appeal Br. 6.) Contrary to Appellant’s argument, the Examiner cites to paragraphs 2, 12, and 32 of Brewer as evidence that the medium taught promotes the survival, viability, and regeneration of neurons in culture, which would maintain the Appeal 2019-005153 Application 14/783,633 5 neurophysiological functions of the cells, rendering the claimed functional properties inherent. (See Ans. 11–12.) We also disagree that Stepan is controlling under the facts of this case. According to Appellant, Stepan prohibits burden shifting when a claim comprises functional properties in addition to overlapping ranges. (See Appeal Br. 7–8, 10–11; see Reply Br. 2–3.) In Stepan, the prior art composition had a cloud point of at least 50o C and ideally 60o C, which was different than the claimed cloud point of at least 70o C. See Stepan, 868 F.3d at 1345. The Stepan court explained that the cloud point limited and defined the scope of what surfactant combinations satisfied the claimed composition. (See id. at 1348.) Thus, under the facts of Stepan, the effect of the prior art composition was different from the effect of the claimed composition. In contrast, the Examiner points to portions of Brewer providing a reasonable basis that the medium it teaches achieves the same results as the claimed medium. Even though Brewer does not expressly state the functional results recited in Appellant’s claim 1 (survival, synaptic function, action potential generation, energetic maintenance), it does teach that the medium promotes the survival and regeneration, and maintains the viability of adult human neurons and maintains neural cells for many weeks. (See Brewer ¶¶ 2, 12, 32.) Brewer teaches that such conditions allow for the appearance of the synaptic elements, including synaptic boutons, synaptic vesicles, and postsynaptic densities. (See id.) We are persuaded that these teachings provide a sufficient basis for the Examiner to conclude the medium of Brewer would produce the functional results recited in claim 1 because it is reasonable to find that one of ordinary skill would have Appeal 2019-005153 Application 14/783,633 6 considered the functions of neural cells to follow from the long-term culture of neural cells that supports expression of typical synaptic structures. Because the Examiner had a reasonable basis to conclude that the functional properties recited in claim 1 would result from the medium taught in Brewer, we are persuaded that the burden properly shifted to Appellant to show otherwise. Contrary to Appellant’s argument in footnote 1 of the Appeal Brief, In re Best, 562 F.2d 1252, 1255 (CCPA 1977), is controlling because of the Examiner’s reasonable basis for finding the functional properties of the claimed cell medium would be met by the mediums taught in Brewer. In Best, the court explained: Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke, supra [441 F.2d 660 (CCPA 1971)]. Whether the rejection is based on ‘inherency’ under 35 USC 102, on “prima facie obviousness” under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. See In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972). (Id.) We are therefore persuaded that, because the effects of the medium of Brewer are the same as the effects recited in claim 1, it is Appellant’s burden to provide evidence showing that culture in the medium of Brewer would not result in the functional characteristics recited in Appellant’s claims. Appellant fails to direct us to this evidence. Appellant also argues that the Examiner improperly relied on Ziegler to show that the teaching in Brewer of improving cell viability would be understood to be improving metabolic activity or energetic maintenance as Appeal 2019-005153 Application 14/783,633 7 recited in claim 1. (See Appeal Br. 9–10; see Reply Br. 4–5.) Appellant argues that Zieger uses a specific assay (the MTT assay), which measures cell viability, with a galactose challenge assay to measure cell respiration. (See Appeal Br. 9.) According to Appellant cell viability is not a direct measurement of cell respiration or energy maintenance. (See id.) We are not persuaded by Appellant’s argument because Appellant does not direct us to, and we do not find, a definition of the claim term “energetic maintenance” that would not be met by viable cells. In the Reply Brief, Appellant argues that “energetic maintenance is an aspect of neurophysiological function that is independent of cell viability” (Reply Br. 5), but the portions of the Specification Appellant cites do not explain why cell viability does not indicate “energetic maintenance.” Specifically, Appellant cites page 34, lines 20–21 of the Specification, which states: “DMEM and Neurobasal medium were specifically optimized to promote the survival of cells in vitro.” (See Reply Br. 5.) This portion fails to indicate anything about energy or to explain what is meant by the claim term “energetic maintenance.” Appellant argues further, citing the Specification at page 39:18–25, that “energetic maintenance is suboptimal in neural cells cultured in DMEM and Neurobasal media, where cells exhibit chronically open synaptic and extra-synaptic passive ionotropic channels leading to the consumption of a considerable amount of cellular energy.” (Reply Br. 5.) The Specification indicates that “[i]f a large number of synaptic and extra-synaptic passive ionotropic channels are chronically open, as reported here for DMEM and Neurobasal, the pumps will fight against the gradients in vain, which is likely to waste a considerable amount of cellular energy.” (Spec. 39:22–25.) Appeal 2019-005153 Application 14/783,633 8 Although this portion of the Specification refers to conditions in which energy is wasted, it is still unclear how the claim term “energetic maintenance” is defined. (See Ans. 15.) It is not clear from Appellant’s Specification whether a cell can have some degree of energy “waste” and still be in a state of “energetic maintenance” or whether the term requires 100% conservation of energy and how that would be achieved. Furthermore, if the ionic pumps in the neural cell membrane “fight against the gradients in vain,” as disclosed by the Specification, a person of ordinary skill in the art would understand this to mean that cellular homeostasis cannot be maintained under such circumstances, with the consequent negative attendant effects on cell viability. Accordingly, we are not persuaded by Appellant’s argument that the Examiner improperly relied on Ziegler. Furthermore, and more importantly, the portions of the Specification cited by Appellant fail to indicate that the medium used in Brewer or the conditions of its use to maintain viable cells as stated by Brewer – maintenance in culture for many weeks, appearance of synaptic boutons, synaptic vesicles, and post-synaptic densities – would be possible without “energetic maintenance.” Accordingly, we are not persuaded that the portions of the Specification cited by the Examiner indicate that there is not a reasonable basis to conclude that the medium of Brewer would produce the same functional results recited in claim 1. Appellant argues further that the Examiner failed to provide sufficient reasoning why only routine optimization is required to select the claimed cell medium components and why there would have been a reasonable expectation of success in doing so. (See Appeal Br. 10–12.) According to Appeal 2019-005153 Application 14/783,633 9 Appellant, the Examiner fails to provide sufficient reasoning for optimization to achieve the recited properties of the claimed medium. (See Appeal Br. 11.) Appellant acknowledges that paragraph 4 of Brewer teaches adjusting certain components, but argues that such optimization would not have provided any motivation to adjust a medium to achieve the recited properties of cell survival and “in vivo-like neurophysiological function” recited in claim 1. (See Appeal Br. 11–12.) According to Appellant, the Examiner fails to explain why a person of ordinary skill would have had a reasonable expectation of success in doing so. (See id. at 12.) We are not persuaded by these arguments because, as explained above, the teachings in Brewer of survival, regeneration, viability, and neurophysiological features in cells cultured for many weeks would have provided a reasonable basis for one of ordinary skill in the art to have expected the functions recited in claim 1 to also be achieved with the medium taught. Because Brewer also teaches that optimizing the components of culture media to achieve different effects was known, we are persuaded that one of ordinary skill would have considered it obvious to have adjusted the concentrations of the components of the medium taught in Brewer to optimize the claimed effects. (See Brewer ¶ 4; see Ans. 7.) “Normally it is to be expected that a change in temperature, or in concentration, or in both, would be an unpatentable modification,” absent a showing that the claimed ranges claimed produce a new and unexpected result which is different in kind and not merely in degree from the results of the prior art. In re Aller, 220 F.2d 454, 456 (C.C.P.A. 1955). Appellant fails to persuade us that the claimed concentrations produce new or unexpected results from the results reported in Brewer. Appeal 2019-005153 Application 14/783,633 10 We are not persuaded by the arguments Appellant presents that the Examiner erred in rejecting claim 1. Appellant does not present separate arguments for the patentability of dependent claims 2, 5–16, 18, and 19 over the Examiner’s obviousness rejection. Accordingly, we are not persuaded that the Examiner erred in rejecting these claims. The Examiner also rejected claims 3, 4, and 17 under 35 U.S.C. § 103 over Brewer, Zeiger, Spiliotopoulos, Espinosa, Espinosa del los Monteros8, and Kido9. (Ans. 8–10.) Claims 3 and 4 provide further limitations of the ranges of L-aspartic acid, L-glutamic acid, respectively. (See Appeal Br. 16–17.) Claim 17 recites cell medium further comprising the light sensitive agent, HEPES. (See Appeal Br. 19.) Appellant argues that combining the “disclosure of Espinosa de los Monterose and Kido with Brewer fails to remedy the deficiencies of Brewer, as neither Espinosa de los Monterose nor Kido disclose nor suggest a cell culture medium comprising the claimed components in amounts effective to produce the recited functional properties.” (Appeal Br. 13.) Because we determine there is no deficiency in the Examiner’s rejection of claim 1 over Brewer, Zieger, and Spiliotopoulos, we are not persuaded by Appellant’s argument that the Examiner erred in rejecting claims 3, 4, and 17. 8 Espinoza de los Monteros and de Vellis, U.S. Patent Application Publication 2012/0052577, published March 1, 2012. 9 Kido, U.S. Patent Application Publication 2012/0177614 A1, published July 12, 2012. Appeal 2019-005153 Application 14/783,633 11 Conclusion Upon consideration of the record and for the reasons given, we affirm the Examiner’s rejection. In summary: Claims Rejected 35 U.S.C. § Basis Affirmed Reversed 1, 2, 5–16, 18, 19 103 Brewer, Zeiger, Spiliotopoulos 1, 2, 5–16, 18, 19 3, 4, 17 103 Brewer, Zeiger, Spiliotopoulos, Espinosa del los Monteros, Kido 3, 4, 17 Overall Outcome 1–19 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. 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