Ex Parte 6,777,231 et alDownload PDFPatent Trial and Appeal BoardJul 31, 201795001592 (P.T.A.B. Jul. 31, 2017) Copy Citation UNITED STATES PATENT AND TRADEMARKOFFICE 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. 95/001,592 04/01/2011 6,777,231 606512800500 8338 23460 7590 11/30/2017 LEYDIG VOIT & MAYER, LTD TWO PRUDENTIAL PLAZA, SUITE 4900 180 NORTH STETSON AVENUE CHICAGO, IL 60601-6731 EXAMINER PONNALURI, PADMASHRI ART UNIT PAPER NUMBER 3991 MAIL DATE DELIVERY MODE 11/30/2017 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ UNIVERSITY OF PITTSBURGH OF THE COMMOMWEALTH SYSTEM OF HIGHER EDUCATION (Patent Owner and Appellant) v. CELLERIX (Requester and Cross-Appellant) ____________ Appeal 2016-008300 Reexamination Control 95/001,592 US Patent 6,777,231 B1 Technology Center 3900 ____________ Before LORA M. GREEN, RICHARD M. LEBOVITZ, and RAE LYNN P. GUEST, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. REQUEST FOR REHEARING This is a request for rehearing under 37 C.F.R. § 41.79(a)(1) (“Req. Reh’g”) of the 37 C.F.R. 41.77(f) Decision (“41.77f Dec.”) entered July 31, 2017. The request is made by the Requester in the above identified inter partes reexamination. The patent under reexamination is US Patent No. 6,777,231 B1 (“the ’231 patent”). Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 2 OBVIOUSNESS BASED ON HAUNER Requester requests reconsideration of the decision not to adopt the rejection of claims 11–15, 17, 18, and 21–24 based on the Hauner publication. Claims 11 and, representative of the appealed claims, are reproduced below: 11. An isolated adipose-derived stem cell that can differentiate into two or more of the group consisting of a bone cell, a cartilage cell, a nerve cell, or a muscle cell, wherein the isolated adipose-derived stem cell is substantially free of other adipose tissue cells and extracellular matrix material, and which can be cultured for at least 15 passages without differentiating, wherein the cell is cultured in DMEM and 5-15% serum for the at least 15 passages without losing the capacity to differentiate. 12. An isolated adipose-derived stem cell that differentiates into two or more of the group consisting of a fat cell, a bone cell, a cartilage cell, a nerve cell, or a muscle cell, wherein the isolated adipose-derived stem cell is substantially free of other adipose tissue cells and extracellular matrix material, and which can be cultured for at least 15 passages without differentiating, wherein the cell is cultured in DMEM and 5-15% serum for the at least 15 passages without losing the capacity to differentiate. Vivotecnia In an attempt to demonstrate that Hauner describes cells which anticipate the claimed adipose-derived stem cells, Requester provided a report by Vivotecnia Research S.L. (Study Director is listed as Covadonga Pañeda, Ph.D.), a test facility, which was said to have isolated cells by Hauner’s protocol. 41.77f Dec. 17. In the 41.77f Decision, we did not find Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 3 the report adequate to establish that Hauner’s cells inherently possessed all the characteristics of the claimed cells. The Decision stated: Vivotecnia did not perform experiments to determine whether such cells were capable of differentiating into adipocyte cells [claim 12] and one of the other cell types recited in the claims. The ’231 patent, in Example 3 (col. 15, l. 36), showed that not all cells isolated by its protocol retained the ability to differentiate into all terminal cell types recited in . . . [the claims]. As discussed in more detail below with respect to the cells of Zilberfarb, there is sufficient evidence of record regarding heterogeneity within the isolated cell populations to explain the differences between the claimed stem cells, the precursor cells of Hauner, and those isolated in the Vivotecnia report. 41.77f Dec. 18. Requester cites to a second declaration by Mario Delgado, Ph.D. (executed Sept. 30, 2011) (“2nd Delgado Decl.”) as providing evidence that the cells described in Vivotecnia were capable of differentiation into the recited cell types. Req. Reh’g 3. Dr. Delgado tested the cells after the second passage and found that they differentiated into muscle and neuronal cells. 2nd Delgado Decl. ¶ 45 (“I understand that cells at passage 2 were sent by Vivotecnia to Cellerix. Cellerix then provided me with the cells. . . . I then induced myogenic and neuronal differentiation in the cells with my colleague by culturing cell samples in differentiation media.”). However, the claims require the cells “cultured for at least 15 passages without differentiating, wherein the cell is cultured in DMEM and 5-15% serum for the at least 15 passages without losing the capacity to differentiate.” Dr. Delgado did not show that the cells did not lose the capacity to differentiate after 15 passages, but rather looked Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 4 at passage 2. Thus, Dr. Delgado did not demonstrate that the cells meet all the limitations in the claims. GPDH (glycerol-3-phosphate dehydrogenase) Requester, without citing any objective evidence, contends that the “Board has misinterpreted the GPDH data in Hauner as meaning cells could not differentiate into adipose cells.” Req. Reh’g 4. The 41.77f Decision cited disclosure from Hauner that, after a second subculture, GPDH was not detected in cells. 41.77f Dec. 16–17 (citing FF9). In other words, the cells had lost the ability to differentiate. The 41.77f Decision explained, citing Hauner’s Abstract, that GPDH is a marker for adipose cell differentiation and thus the lack of GPDH would indicate the failure of cells to differentiate. Id. Hauner’s Abstract makes it clear that GPDH was used as a marker for adipose differentiation, as well as lipid accumulation, and one other enzyme marker: “cells were able to undergo terminal adipose differentiation within 18 d, as assessed by lipid accumulation and the expression of lipoprotein lipase (LPL) and glycerol-3- phosphate dehydrogenase (GPDH) activities.” Thus, we do not agree with Requester that the GPDH data was misinterpreted. The original Decision on Appeal (“DOA”) (entered Nov. 27, 2013) referenced both markers and cited Hauner’s disclosure on page 1666 for its teaching that exposure of the cells to serum resulted in loss of differentiation capacity. DOA 20–21. Requester did not identify a defect in the findings nor the conclusion based upon it, other than to deny them. Reply Br. 4–5. Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 5 Requester also states that the Board failed to address the differences in conditions for adipocyte differentiation between Hauner and the ’231 Patent. Req. Reh’g 4. Request contends that the conditions disclosed in the ’231 patent would have resulted in adipocyte differentiation using the cells of Hauner. Id., 5. Requester also cited the second declaration of Dr. Marion Delgado stating: As can be seen from a comparison of Hauner and Zuk 2001, Hauner at most used three adipogenic induces (insulin, cortisol and IBMX), while Zuk 2001 uses four adipogenic inducers (insulin, dexamethasone, IBMX, and indomethacin). Moreover, Zuk 2001 used adipogenic inducers at concentrations that were higher than that used in Hauner. For example, Zuk 2001 used 10 µM insulin, which is 20 times more than the 0.5 µM insulin used by Hauner. Moreover, Zuk 2001 used 0.5 mM IBMX, which is twice as much as the 0.25 mM IBMX used by Hauner. Based on these differences, it is my opinion that a skilled artisan would have concluded that the differences in the number and amounts of adipogenic inducers could have accounted for the differences in adipogenic lineage differentiation capacity rather than the length of time that the cells were cultured in serum. 2nd Delgado Decl. ¶ 44. Requester states that, in contrast to Hauner, the ’231 patent “uses four adipogenic inducers at significantly higher concentrations.” Req. Reh’g 4. This argument is not persuasive. Requester has the burden to show that the claim is unpatentable. Requester did not meet that burden. Based on the teaching in Hauner that its cells lost the ability to differentiate after two passages, there is reasonable factual basis to conclude that the cells in Hauner do not meet the limitation of claim 11 and others that the cells must be “cultured in DMEM and 5-15% Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 6 serum for the at least 15 passages without losing the capacity to differentiate.” (Emphasis added.) Requester did not provide sufficient factual evidence to rebut or undermine this reasonable belief that the cells are different based on the explicit factual teaching in Hauner. Although Dr. Delgado stated that the differences in adipogenic inducers “could have accounted for the differences in adipogenic lineage differentiation capacity rather than the length of time that the cells were cultured in serum,” he did not provide evidence that the inducers, in fact, did account for the difference, but rather merely conjectured – with no supporting evidence – they “could have” made a difference. 2nd Delgado Decl. ¶ 44. Dr. Delgado also stated that “the induction method used by Zuk is a much more potent inducer of adipogenisis [sic, adipogenesis] than that used by Hauner,” but Dr. Delgado merely identified the differences in chemicals and concentrations used between the publications without demonstrating or providing scientific reasoning that such differences affected a cell’s differentiation capacity. Id., ¶¶ 43, 44. Absent such evidence or scientific explanation, we conclude that Requester did not meet the burden of establishing that Hauner’s cells are the same as those which are claimed. Secondly, if the claims are interpreted to require that the cells were actually “cultured in DMEM and 5-15% serum for the at least 15 passages without losing the capacity to differentiate” (41.77f Dec. 10, 16–17), then the claimed cells cannot be anticipated by Hauner’s cells which were passaged only twice and then found to have lost their capacity to differentiate. Id. Under this interpretation, even if Dr. Delgado’s opinion Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 7 testimony is adopted (2nd Delgado Decl. ¶ 44), it is irrelevant whether the induction protocol is responsible for the differences in cell capability because the actual and only protocol used by Hauner resulted in the loss of differentiation capability after two passages. Requester also contends: Hauner measures differentiation capacity by detecting glycerol- 3-phosphate dehydrogenase (GPDH) activity, while the ‘231 specification measures differentiation capacity by looking at the accumulation of lipid droplets by staining with Oil red O (see ‘231 patent at Col. 14, line 60). One of skill in the art would not assume that different metrics would yield similar outcomes, but instead would expect different outcomes when using different metrics. Req. Reh’g 4. Requester has provided no evidence that different “metrics” would lead to different outcomes. . However, again, Requester provides no scientific evidence or reasoning to support this statement about different metrics having different outcomes. To the contrary, Hauner reports using both lipid accumulation and GPDH to determine a cell’s ability to undergo adipose differentiation (Hauner, Abstract), and noted the consistency of both markers: It must be recalled that a good correlation between the proportion of differentiated triacylglycerol-containing cells and the specific activity of GPDH occurred both for human stromal- vascular cells (12) and mouse Ob17 cells (20). Furthermore, histochemical staining of GPDH was only observed in clusters of lipid-containing cells (13). Hauner 1666. Thus, Requester’s argument is contrary to the actual teaching in Hauner. Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 8 In sum, Requester did not persuasively identify an error in the decision not to adopt the anticipation rejection based on Hauner. WRITTEN DESCRIPTION Patent Owner again contends that ’231 patent fails to describe or enable an “isolated adipose-derived stem cell” which, inter alia, “can be cultured for at least 15 passages without differentiating, wherein the cell is cultured in DMEM and 5-15% serum for the at least 15 passages without losing the capacity to differentiate.” In other words, the cells do not lose the capacity to differentiate after being passaged at least 15 times. The 41.77f Decision cited disclosure in the ’231 patent stating “the cells can be passaged at least five times in such medium without differentiating, while still retaining their developmental phenotype” and “without losing developmental phenotype.” 41.77f Dec. 5. Requester appears to question whether retaining “developmental phenotype” is the same as “without losing the capacity to differentiate.” Req. Reh’g 5. However, this was explained in the original Decision on Appeal: The stem cells of claims 11 and 25 can be cultured in DMEM and 5-15% serum “without losing the capacity to differentiate.” The latter phrase is explained in the ‘231 Patent. According to the patent, “[a] stem cell is a pluripotent cell that has the capacity to differentiate in accordance with at least two discrete developmental pathways.” (‘231 Patent, col. 18, ll. 10-12; emphasis added.) A cell that has differentiated along a “developmental pathway” is one that differentiated into a given developmental phenotype (id. at col. 6, ll. 25-33). “A developmental phenotype is the potential of a cell to acquire a particular physical phenotype through the process of differentiation.” (Id. at col. 18, ll. 3-5.) In other words, the Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 9 “capacity to differentiate” means the ability of the claimed stem cell to differentiate into two or more of the cell types (a “physical phenotype”) selected from the group consisting of a fat cell, a bone cell, a cartilage cell, a nerve cell, or a muscle cell. DOA 4. With respect to the reference to original claims 1, 2, and 3 as supporting the written description (41.77f Dec. 5–6), we have considered Requester’s argument, but do not find it persuasively demonstrates an error in the Decision. Claim 2 clearly recites the ability to differentiate after 15 passages and claim 3, which depends from it, as clearly lists the developmental phenotypes of the cell. Since claim 3 adds a limitation to claim 2, the skilled worker would understand that the cell of claim 3 has the attributes of claim 2 (“can be cultured in DMEM + about 10% fetal bovine serum for at least 15 passages without differentiating”) and claim 3 (the recited developmental phenotypes). Requester misapprehends original claim 3 by asserting “[o]ne of skill in the art would read the developmental phenotypes of claim 3 as applying to the cell of claim 2, not the multitudinous offspring of the cell of claim 2 after undergoing 15 passages.” Req. Reh’g. 6. Requester’s construction of the claim ignores and reads out the express limitation that claim 2 covers cells which have been passaged 15 times. In addition, we have considered Requester’s contention that the inventors did not test their cells for differentiation capacity after passaging 15 times in the claimed medium. Id. We find this argument to be unpersuasive. The recited passages (see DOA 4; 41.77f Dec. 5–6); and claims convey that the inventors possessed the idea of passaging cells for 5, Appeal 2016-008300 Reexamination Control No. 95/001,592 Patent 6,777,231 B1 10 10, 15, and 20 times without differentiating and without losing developmental potential. If the cells did not lose developmental potential, the inventors clearly had to test to determine that the potential was not lost. REHEARING DENIED PATENT OWNER: LEYDIG VOIT & MAYER, LTD TWO PRUDENTIAL PLAZA, SUITE 4900 180 NORTH STETSON AVENUE CHICAGO, IL 60601-6731 THIRD PARTY REQUESTER: ROBERT A. SALTZBERG MORRISON & FOERSTER LLP 425 MARKET STREET SAN FRANCISCO, CA 94105-2482 Copy with citationCopy as parenthetical citation