Ex Parte Ueda et alDownload PDFPatent Trial and Appeal BoardMay 23, 201813637107 (P.T.A.B. May. 23, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/637,107 12/13/2012 Minoru Ueda 22910 7590 05/25/2018 BANNER & WITCOFF, LTD. 28 STATE STREET SUITE 1800 BOSTON, MA 02109-1701 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 007801.00003 1085 EXAMINER CORDAS, EMILY ANN ART UNIT PAPER NUMBER 1651 NOTIFICATION DATE DELIVERY MODE 05/25/2018 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): PT0-2291 O@bannerwitcoff.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MINORU UEDA, YOICHI YAMADA, KATSUMI EBISA WA, AKIHITO YAMAMOTO, KIYOSHI SAKAI, KOHKI MATSUBARA, HISASHI HATTORI, MASAHIKO SUGIYAMA, and TAKANORI INOUE 1 Appeal2017-007066 Application 13/637, 107 Technology Center 1600 Before ERIC B. GRIMES, JOHN G. NEW, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a composition for repairing damaged tissue, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE "Stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth dental pulp stem cells (DPSCs) derived from wisdom tooth, 1 Appellants identify the Real Party in Interest as NATIONAL UNIVERSITY CORPORATION NAGOYA UNIVERSITY. Br. 2. Appeal2017-007066 Application 13/637, 107 which are medical wastes, were identified as novel stem cell groups having self-renewal capacity and pluripotency similar to those of BMSCs [bone marrow stem cells]." Spec. i-f 6. Claims 1, 2, 9, 10, and 24 are on appeal. Claim 1 is illustrative and reads as follows: 1. A damaged part treatment composition for repairing a damaged part of a target tissue, the composition comprising a dental pulp stem cell-conditioned medium which does not comprise any serum, wherein the medium comprises vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and transforming growth factor B (TGF-B), and wherein the medium further comprises a neurite outgrowth activity in the presence of a nerve regeneration inhibitory substance or an apoptosis inhibitory activity toward neuronal cells. DISCUSSION The Examiner has rejected claims 1, 2, 9, 10, and 24 under 35 U.S.C. § 103(a) as obvious based on Iohara, 2 Gandia, 3 Tran-Hung, 4 Nakashima, 5 2 Iohara et al., A Novel Stem Cell Source for Vasculogenesis in Ischemia: Sub fraction of Side Population Cells from Dental Pulp, 26 STEM CELLS 2408 (2008). 3 Gandia et al., Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction, 26 STEM CELLS 638 (2008). 4 Tran-Hung et al., Quantification of angiogenic growth factors released by human dental cells after injury, 53 ARCHIVES OF ORAL BIOLOGY 9 (2008). 5 Nakashima et al., US 2011/0177041 Al, published July 21, 2011. 2 Appeal2017-007066 Application 13/637, 107 Sakai, 6 and Lim. 7 Ans. 3. The Examiner finds that "Iohara teaches a composition comprising of cell-free conditioned medium from stem cells or side population cells from dental pulp (dental pulp stem cells)." Id. at 4. The Examiner finds that "Iohara teaches that the cells express cytokines, including VEGF and HGF, and, therefore, the conditioned medium would inherently contain VEGF and HGF." Id. The Examiner finds that "Gandia reports that dental pulp stem cells express VEGF and IGF," that "Tran-Hung reports dental pulp stem cells express VEGF and PDGF," and that "Nakashima reports dental pulp stem cells express TGF-B." Id. The Examiner also finds that "Sakai teaches dental pulp stem cell (DPSC) conditioned medium restored neurite extension activity of cerebral granular neurons ... and that neurite extension through the inhibition of multiple axon growth inhibitors (AG Is) is a unique characteristic of the DPSCs." Id. at 4--5. The Examiner finds that Iohara' s conditioned medium is not free of serum, as recited in claim 1, but "Lim teaches a composition comprising conditioned cell culture medium from mesenchymal stem cells which does not include serum" and "teaches that there are advantages to using serum- free medium." Id. at 5. The Examiner concludes that it would have been obvious "to use serum-free medium in the composition of Iohara for the 6 Sakai et al., Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro- regenerative mechanisms, 122 J. CLIN. INVEST. 80 (2012). 7 Lim et al., WO 2008/020815 Al, published Feb. 21, 2008. 3 Appeal2017-007066 Application 13/637, 107 benefits of improved reproducibility of the composition and to decrease the possibility of contamination by adventitious agents," as taught by Lim. Id. We agree with the Examiner that the composition of claim 1 would have been obvious to a person of ordinary skill in the art based on the cited references. Iohara discloses "a highly vasculogenic subfraction of side population (SP) cells ... from dental pulp. The CD3I-;CD146- SP cells, demonstrating CD34+ and vascular endothelial growth factor-2 (VEGFR2)/Flkl +,were similar to EPCs [endothelial progenitor cells]." Iohara 2408, Abstract. Iohara reports that these cells showed "multilineage differentiation potential" and "expressed several proangiogenic factors, such as VEGF-A." Id. Iohara also reports that "[t]he expression of angiogenic (VEGF-A, HGF)" cytokines "was stronger in CD3 I-;CD146- SP cells compared with CD3l+;CD146- SP cells." Id. at 2413. Iohara states that "[c]onditioned medium from this [CD3 I-;CD146-J subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source." Id. at 2408, Abstract. Gandia discloses that "[ d]ental pulp stem cells (DPSC) ... are able to secrete vascular endothelial growth factor (VEGF), insulin-like growth factor-I (IGF-1) and -2 (IGF-2)." Gandia 638. Tran-Hung discloses that human dental pulp cells "secreted significant levels of PDGF-AB, VEGF and FGF-2." Tran-Hung 9, Abstract. Nakashima discloses that "dental pulp stem cells ... express larger amounts of neural factors such as BDNF, NPY, TGFB 1, and TGFB3 than those of, for example, bone marrow stem cells and 4 Appeal2017-007066 Application 13/637, 107 adipose stem cells." Nakashima i-f 87. Sakai discloses that human dental pulp stem cells "inhibited the SCI-induced apoptosis of neurons" and "promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors." Sakai 80, Abstract. Lim discloses a method of preparing a conditioned cell medium by culturing mesenchymal stem cells (MS Cs) and isolating the cell culture medium. Lim, Abstract. "In particular, MSCs may be made by propagating a cell obtained by dispersing a embryonic stem (ES) cell colony, or a descendent thereof, in the absence of co-culture in a serum free medium comprising FGF2." Id. at 12. The serum-free media may comprise chemically-defined media in which all components have a known chemical structure. Chemically-defined serum-free media is advantageous as it provides a completely defined system which eliminates variability[,] allows for improved reproducibility and more consistent performance, and decreases [the] possibility of contamination by adventitious agents. Id. at 17. Thus, it would have been obvious to a person of ordinary skill in the art to modify Iohara's method of producing a conditioned medium from dental pulp stem cells by using a serum-free medium, because Lim teaches that using a (chemically-defined) serum-free medium eliminates variability, allows for more consistent performance, and decreases the possibility of contamination. We therefore agree with the Examiner that the composition of claim 1 would have been obvious based on the cited references. Appellants do not dispute the Examiner's findings that, as evidenced by Iohara, Gandia, Tran-Hung, and Nakashima, dental pulp stem cells produce VEGF, HGF, IGF, PDGF, and TGF-B, and therefore conditioned 5 Appeal2017-007066 Application 13/637, 107 medium from such cells would contain these factors. See Br. 6, 9. Appellants also do not dispute that, as evidenced by Sakai, dental pulp stem cell-conditioned medium comprises neurite extension activity in the presence of axon growth inhibitors (i.e., "nerve regeneration inhibitory substance[ s ]," as recited in claim 1 ). See id. at 9. Appellants argue, however, that Ioh[ a ]ra is merely concerned with a subfraction of side population (SP) cells based on CD31 and CD 146. This is in stark contrast to the claimed composition which is directed to dental pulp stem cells that are not disclosed to be fractionated. Therefore, the cell source that generated the conditioned medium in Ioh[a]ra is different from that as presently claimed. . . . [T]he compositions of conditioned media vary depending on the source cells. Id. at 6. This argument is unpersuasive, because Iohara expressly states that its CD31-, CD 146- "subfraction of SP cells from dental pulp is a new stem cell source." Iohara 2408, Abstract (emphases added). Thus, Iohara's disclosure supports the Examiner's finding that Iohara discloses stem cells from dental pulp, and medium conditioned by such cells. As the Examiner pointed out, "the claim language includes conditioned medium from all types of dental pulp stem cells" and "does not exclude subpopulations of dental pulp stem cells." Ans. 7. As the Examiner also pointed out, id., Appellants have not pointed to evidence showing that Iohara' s dental pulp stem cells produce a conditioned medium that differs from that defined by claim 1. Appellants also argue that "the conditioned media of Ioh[ a ]ra is further different from the claimed composition because it is not serum free. 6 Appeal2017-007066 Application 13/637, 107 ... [C]onditioned media containing residual serum is unsuitable for administration." Br. 6-7. As we understand it, Appellants' argument is that Iohara's conditioned medium is not a "damaged part treatment composition," as recited in claim 1, because it is unsuitable for administration. However, as the Examiner pointed out, Ans. 8, the rejection is based on a combination of Iohara's teaching of dental pulp stem cells and Lim's teaching of the advantages of using serum-free media for stem cells. Thus, the composition made obvious by the combined teachings of the references is a serum-free conditioned medium from dental pulp stem cells. Whether Iohara's composition itself would be considered a "damaged part treatment composition" is not germane to the basis of the rejection. Appellants also argue that "the cell source that generated the conditioned medium in Lim is different from that as presently claimed. In other words, Lim does not teach a composition comprising a dental pulp stem cell-conditioned medium as presently claimed since it merely teaches conditioned media from mesenchymal stem cells." Br. 7. Again, however, the rejection is based on the combined teachings of the cited references, and the composition made obvious by those teachings is a serum-free conditioned medium from dental pulp stem cells. Appellants argue that "Lim only teaches a serum-free medium at the initial stage of differentiating embryonic stem (ES) cells into mesenchymal stem cells. In later stages, the mesenchymal stem cells were cultured in media in the presence of serum." Id. Similarly, Appellants argue that "Lim merely discloses use of a serum free medium comprising FGF2 when 7 Appeal2017-007066 Application 13/637, 107 obtaining MSCs by culturing ES cells ... , and Lim does not provide a motivation to use a serum free medium for preparing a conditioned medium." Id. at 8-9. This argument is also unpersuasive. Lim states that "[ m ]edia for isolating and propagating pluripotent stem cells can have any of several different formulas." Lim 43 (emphasis added). Lim provides exemplary serum-containing and serum-free media. Id. at 43--44. As the Examiner pointed out, Ans. 12, Lim provides examples that describe culturing stem cells (embryonic stem cell-derived mesenchymal stem cells, or ESC-MSCs) in serum-free media: Examples 7 to 15 describe experiments to analyse the proteome of human ESC-derived MSCs (hESC-MSCs). In these experiments, a chemically defined serum-free culture media is conditioned by human ESC-derived MSCs (hESC- MSCs) [and] analysed using a clinically compliant protocol. Lim 60. Appellants have not pointed to evidence showing that a person of ordinary skill in the art would not have expected Iohara's dental pulp stem cells to likewise be amenable to culturing in serum-free media. We affirm the rejection of claim 1 under 35 U.S.C. § 103(a). Claims 2, 9, 10, and 24 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY We affirm the rejection of claims 1, 2, 9, 10, and 24 under 35 U.S.C. § 103(a) based on Iohara, Gandia, Tran-Hung, Nakashima, Sakai, and Lim. 8 Appeal2017-007066 Application 13/637, 107 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 9 Copy with citationCopy as parenthetical citation