Ex Parte Ho et al

Patent Trial and Appeal BoardNov 26, 2012

11054824 (P.T.A.B. Nov. 26, 2012)

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. 11/054,824 02/10/2005 Tony W. Ho 2560.0020001/JAG/CMB 2664 26111 7590 11/26/2012 STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C. 1100 NEW YORK AVENUE, N.W. WASHINGTON, DC 20005 EXAMINER LANKFORD JR, LEON B ART UNIT PAPER NUMBER 1651 MAIL DATE DELIVERY MODE 11/26/2012 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 __________ Ex parte TONY W. HO, GENE C. KOPEN, WILLIAM F. RIGHTER, J. LYNN RUTKOWSKI, and JOSEPH WAGNER __________ Appeal 2011-009671 1 Application 11/054,824 Technology Center 1600 __________ Before TONI R. SCHEINER, LORA M. GREEN, and ULRIKE W. JENKS, Administrative Patent Judges. SCHEINER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 1-6, 15-30, and 39-45, directed to a method of producing an isolated population of cells which co-expresses CD49c and CD90. The claims have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). 1 This appeal is related to Appeal No. 2011-002458 (in Application No. 09/960,244), and Appeal No. 2011-009014 (in Application No. 10/251,685). We have considered the three appeals together. Appeal 2011-009671 Application 11/054,824 2 STATEMENT OF THE CASE Claims 1-6, 15-30, and 39-45 are pending and on appeal. Claims 7-14, 31-38, and 46-68 are also pending, but have been withdrawn from consideration (App. Br. 7). As an initial matter, we note that according to the Examiner, in response to an election of species requirement, Appellants elected a “species represented by a „cell culture density‟ comprising a seeding density of less than about 30 cells/cm 2 ; a „starting cell population‟ comprising human bone marrow; and, a „culture oxygen concentration‟ comprising about 5% oxygen” (Ans. 5-6 (emphasis omitted)). It is our understanding that the claims have been examined only to the extent they read on the elected species. With that in mind, Claim 1 is representative of the subject matter on appeal: 1. A method of producing an isolated cell population wherein greater than about 91% of the cells in said cell population co-express CD49c and CD90, comprising the steps of: a) providing a source population of cells; and, b) culturing said source cell population at a seeding density of less than about 100 cells/cm 2 under a low oxygen condition. The Examiner relies on the following evidence: Haynesworth et al. US 5,733,542 Mar. 31, 1998 Manfred R. Koller et al., Beneficial Effects of Reduced Oxygen Tension and Perfusion in Long-Term Hematopoietic Cultures, 665 ANNALS NEW YORK ACADEMY OF SCIENCES 105-116 (1992). The Examiner rejected claims 1-6, 15-30, and 39-45 under 35 U.S.C. § 103(a) as unpatentable over Haynesworth and Koller (Ans. 3-5). We reverse. Appeal 2011-009671 Application 11/054,824 3 FINDINGS OF FACT 1. Haynesworth discloses a population of mesenchymal stem cells (MSCs), “normally present at very low frequencies in bone marrow and other mesenchymal tissues” (Haynesworth, col. 1, ll. 25-26). Briefly, bone marrow from iliac crest is fractionated; cells are collected from a low density fraction (1.03 g/ml); then further purified and expanded “in complete medium . . . at 37° C. in humidified atmosphere containing 95% air and 5% CO2” (id. at col. 4, ll. 19-24). 2. The concentration of oxygen (O2) in air is about 21% (see http://www.universetoday.com/26656/composition-of-the-earths- atmosphere/). Thus, Haynesworth‟s cells were cultured in an atmosphere containing about 19.95% oxygen. 3. Koller teaches that Most experiments in bone marrow culture are carried out in a fully humidified gas phase containing 5% CO2 and 20% O2. This level of oxygen is substantially higher than the in vivo cellular environment, especially in the case of bone marrow. In fact, earlier experiments have shown that the formation of hematpoietic cell colonies in semisolid culture is significantly enhanced under reduced oxygen conditions, resulting in both larger and more numerous colonies. (Koller 105.) ISSUE The Examiner finds that Haynesworth “teach[es] culturing bone marrow cells in a reduced oxygen environment and then selecting non- adherent cells and identifying them as mesenchymal stem cells (now known to express CD90 and CD49c)” (Ans. 3). The Examiner acknowledges that Haynesworth does not use a “„culture oxygen concentration‟ comprising Appeal 2011-009671 Application 11/054,824 4 about 5% oxygen” (id. at 4). However, the Examiner finds that Haynesworth “recognized the desire to reduce the oxygen concentration from ambient concentration,” and therefore “identified „culture oxygen concentration‟ as a result effective variable and as such „culture oxygen concentration‟ would have been routinely optimized at the time the invention was made” (id. at 4). With respect to the cell concentration used, the Examiner argues that “[t]he same discussion above applies” (id. at 5). The Examiner finds that Koller also identifies “culture oxygen concentration[] as a result effective variable because Koller teaches culturing mononuclear cells at several different oxygen concentrations including 5% O2 or less and . . . indicates that culturing at under 5% resulted in increased cell number and increased survival” (id. at 4). The issue raised by this rejection is whether the preponderance of the evidence of record supports the Examiner‟s conclusion that it would have been obvious for one of ordinary skill in the art to culture Haynesworth‟s mesenchymal stem cells at a seeding density of less than about 100 cells/cm 2 under a low oxygen condition. We will reverse this rejection. First, we agree with Appellants that the Examiner‟s finding that Haynesworth‟s method produces a cell population “known to express CD90 and CD49c” is not supported by the evidence of record (see the opinions in related appeals 2011-002458 and 2011-009014). Second, the evidence of record shows that the atmosphere used by Haynesworth to culture MSCs, i.e., 95% air and 5% CO2, is commonly used in culturing mammalian cells (FF3), and we agree with Appellants that it would not have been considered “a low oxygen condition” by one of ordinary skill in the art. Moreover, Haynesworth does not specifically Appeal 2011-009671 Application 11/054,824 5 mention oxygen, much less indicate that substantially lowering its concentration would have any effect, negative or positive, on the growth or expression of cell surface markers on MSCs. Therefore, we agree with Appellants that there is no basis for the Examiner‟s assertion that Haynesworth identifies oxygen concentration as a result effective variable. While the discovery of an optimum value of a variable in a known process is normally obvious (In re Aller, 220 F.2d 454, 456 (CCPA 1955); see also In re Boesch, 617 F.2d 272, 276 (CCPA 1980)), there is an exception to this general rule, where the parameter optimized was not recognized to be a result effective variable (In re Antonie, 559 F.2d 618, 621 (CCPA 1977)). Third, Koller discloses a low oxygen atmosphere for culturing hematopoietic cells (FF3). The Examiner has not explained why one of ordinary skill in the art would have considered Koller‟s observations to be relevant to Haynesworth‟s mesenchymal stem cells. Finally, the Examiner has not squarely addressed the issue of seeding density. SUMMARY The Examiner‟s conclusion that it would have been obvious for one of ordinary skill in the art to culture Haynesworth‟s mesenchymal stem cells at a seeding density of less than about 100 cells/cm 2 under a low oxygen condition is not supported by a preponderance of the evidence. The rejection of claims 1-6, 15-30, and 39-45 as unpatentable over Haynesworth and Koller is reversed. REVERSED cdc