Ex Parte Racey et al

Patent Trial and Appeal BoardNov 30, 2015

12511210 (P.T.A.B. Nov. 30, 2015)

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. 12/511,210 07/29/2009 Gary Racey 2012-0002 3339 28078 7590 11/30/2015 MAGINOT, MOORE & BECK, LLP One Indiana Square, Suite 2200 INDIANAPOLIS, IN 46204 EXAMINER DUTT, ADITI ART UNIT PAPER NUMBER 1649 MAIL DATE DELIVERY MODE 11/30/2015 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 GARY RACEY, RUSSELL BOWERMASTER, and THOMAS BOB1 __________ Appeal 2013-003778 Application 12/511,210 Technology Center 1600 __________ Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and TAWEN CHANG, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of isolating cells from teeth, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 Appellants identify the Real Party in Interest as inventors Gary Racey, Russell Bowermaster, and Thomas Bob. (Appeal Br. 4.) Appeal 2013-003778 Application 12/511,210 2 STATEMENT OF THE CASE The Specification states that a circle of pulp tissue at the periphery of each developing tooth root adjacent to the epithelial root sheath and epithelial diaphragm [is] known as the “dental papillary ring” or “dental papillary annulus.”[ ] This area of the . . . developing pulp, adjacent to ectodermal structures derived from enamel organ epithelium (EOE), attracts a higher concentration of CNC [cranial neural crest]-derived undifferentiated cells. (Spec. 4 ¶ 8.) Claims 3–6, 8–11, 13, and 14 are on appeal. Claim 3 is the only independent claim and reads as follows: 3. A method of producing a substantially pure in vitro cell culture of non-lineage committed precursor cells (n-LCP) isolated from the dental papillary annulus of teeth in any stage of development, comprising: (a) providing dental tissue in any stage of development from a mammal; (b) dissecting the dental tissue to isolate its dental papillary annulus; (c) culturing the annular tissue as adherent explants on collagen- coated and/or fibronectin-coated culture substrates to isolate n-LCPs characterized by the positive expression of one or more of the following markers: i. Nestin, PDGFRalpha, CD49d (alpha4-integrin), CD56 (N- CAM), CD133; ii. and further characterized by positive expression of one or more of the following marker genes: Sox2, Sox9, Soxl0, Snail1, Snail2, Dlx6, Pcbp4, Msx2, HIfx, Thip1, Vars2, Myo10, 270094K13Rik, Ets1, Pygo2, Adam12, 5730449L18Rik, Rex3, Vdac1, AU041707, Pfn1, Crmp1, Ubc4b; and (d) culturing one or more of the isolated n-LCPs as adherent cells under suitable conditions to obtain a substantially pure population; and Appeal 2013-003778 Application 12/511,210 3 (e) expanding one or more of the isolated n-LCP populations as adherent cells by sub-culture or other suitable means. DISCUSSION The Examiner has rejected claims 3–5, 8, 9, 11, 13, and 14 under 35 U.S.C. § 103(a) based on Ikeda,2 Glycosan,3 Shi,4 Thompson,5 Techawattanawisal,6 and Kollar.7 (Ans. 7.) The Examiner has also rejected all of the claims under 35 U.S.C. § 103(a) based on Ikeda, Glycosan, Shi, Thompson, Techawattanawisal, Kollar, Bowermaster,8 and Sonoyama.9 (Ans. 11.) The same issue is dispositive for both rejections. The Examiner finds, among other things, that Ikeda teaches isolating pluripotent or multipotent cells from dental papilla (id. at 8), that Thompson teaches the isolation of undifferentiated multipotential progenitor cells from 2 Ikeda et al., JP 2006–238875, published Sept. 14, 2006. 3 Glycosan, “Stem Cell Culture,” http://www.glycosan.com/ha_applications/stem_cells.html 1–5 (2007). 4 Shi et al., Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp, 18 JOURNAL OF BONE AND MINERAL RESEARCH 696–704 (2003). 5 Thompson, Proceedings of the Anatomical Society of Great Britain and Ireland, 212 J. ANAT. 74 (2008). 6 Techawattanawisal et al., Isolation of multipotent stem cells from adult rat periodontal ligament by neurosphere-forming culture system, 357 BBRC 917–923 (2007). 7 Kollar et al., The Influence of the Dental Papilla on the Development of Tooth Shape in Embryonic Mouse Tooth Germs, 21 J. EMBRYOL. EXP. MORPH. 131–48 (1969). 8 Bowermaster et al., US Patent Application Publication No. 2007/0258957 A1, published Nov. 8, 2007. 9 Sonoyama et al., Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine,1 PLOS ONE 1–8 (2006). Appeal 2013-003778 Application 12/511,210 4 the dental pulp that express CD56 (id. at 9), and that Techawattanawisal provides evidence that “stem cells isolated from the teeth . . . are neural crest stem cells (as in the dental papilla) and express the mRNA of the Sox2 marker (page 921, col 1, para 2; Figure 1), thereby indicating that the pluripotent cells from the dental papilla will inherently express the Sox2 marker gene.” (Id. at 10.) Appellants argue that the Examiner has “fail[ed] to establish the notion that because some cells in periodontal ligament tissues exhibit the Sox2 marker gene, that dental pulp tissue must inherently display all the same marker genes as periodontal ligament tissue.” (Br. 15.) Appellants argue that “the examiner has failed to even establish that there are any prior references that establish that some dental pulp cells include the Sox2 marker gene.” (Id.) We agree with Appellants that the Examiner has not provided evidence showing that the pluripotent or multipotent cells disclosed by Ikeda or the cells from human dental pulp disclosed by Thompson inherently express Sox2. Ikeda describes obtaining a “mesenchymal stem cell and/or a neural stem cell especially using a human dental papilla.” (Ikeda 1 ¶ 1.) Thompson describes isolating “multipotential progenitor cells from human dental pulp.” (Thompson 74, title.) Techawattanawisal discloses “the isolation of multipotent stem cells from rat periodontal ligament (PDL) using [a] neurosphere-forming culture system.” (Techawattanawisal 917, abstract.) Techawattanawisal states that Appeal 2013-003778 Application 12/511,210 5 the “spheres expressed mRNA of neural crest-associated transcription factors Twist, Slug, Sox2, and Sox9.” (Id.) Techawattanawisal states that “[t]he periodontal ligament (PDL) is a non-mineralized connective tissue which surrounds the tooth and is composed of various cell types.” (Id. at 917, right col.) Thus, in contrast to Ikeda’s method of obtaining stem cells from dental papilla and Thompson’s method of obtaining cells from the dental pulp, Techawattanawisal obtains its Sox2- expressing cells from connective tissue that surrounds the teeth. The Examiner reasons that Techawattanawisal provides evidence that “pluripotent cells from the dental papilla will inherently express the Sox2 marker gene” because it “teaches that the stem cells [isolated from the teeth] are neural crest stem cells (as in the dental papilla) and express the mRNA of the Sox2 marker.” (Ans. 10.) The Examiner also states that both PDL and dental papilla “provide stem cells that are neural crest stem cells.” (Id. at 20.) We conclude that the Examiner’s reasoning is not supported by the evidence of record. Techawattanawisal states that the neurospheres formed in its process “expressed mRNA of various neural crest-derived stem cell (NCSC) markers, such as, Twist, Slug, Sox2, and Sox9.” (Techawattanawisal 921, left col.) However, the Examiner has not pointed to evidence showing that Ikeda’s mesenchymal and/or neural stem cells from the dental papilla or Thompson’s progenitor cells from the dental pulp are also neural crest-derived stem cells. Nor has the Examiner pointed to evidence showing that all neural crest-derived stem cells express the markers described by Techawattanawisal. Appeal 2013-003778 Application 12/511,210 6 In this regard, we note that Ikeda states that its mesenchymal stem cells derived from dental papilla express at least one of CD29, CD90, and CD105 but do not express CD34 or CD45. (Ikeda 9 ¶ 51.) Thompson, by contrast, describes multipotential cells derived from dental pulp that express CD34. (Thompson 74, right col.) Thus, the evidence does not support a conclusion that all stem cells derived from the dental papilla inherently express the same set of surface antigens, or that stem cells derived from the dental papilla inherently express the same surface antigens as stem cells derived from periodontal ligament. Because positive expression of a marker gene such as Sox2 or Sox9 is a limitation of all claims on appeal, and the Examiner relies only on Techawattanawisal and inherency arguments to show this limitation, we reverse the obviousness rejection based on Ikeda, Glycosan, Shi, Thompson, Techawattanawisal, and Kollar for the reasons set forth above. The Examiner relies on the same reasoning with respect to the second ground of rejection. (Ans. 11.) We therefore reverse both of the rejections on appeal. REVERSED sl