Ex Parte Ho et alDownload PDFPatent Trial and Appeal BoardAug 23, 201811797322 (P.T.A.B. Aug. 23, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 11/797,322 05/02/2007 56719 7590 08/27/2018 MEDLER FERRO WOODHOUSE & MILLS PLLC 8201 Greensboro Drive, Suite 1060 McLean, VA 22102 TonyW. Ho 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. 0154-0002US4 6355 EXAMINER KIM, TAEYOON ART UNIT PAPER NUMBER 1651 NOTIFICATION DATE DELIVERY MODE 08/27/2018 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): docketing@medlerferro.com tmedler@medlerferro.com aferro@medlerferro.com 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 1 Appeal2016-007472 2 Application 11/797 ,322 Technology Center 1600 Before TONI R. SCHEINER, ULRIKE W. JENKS, and ELIZABETH A. LA VIER, 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 directed to an isolated cell population of human bone marrow-derived cells. The claims stand rejected under the doctrine of obviousness-type double patenting, and under 35 U.S.C. § 101 as directed to patent-ineligible subject matter. We have jurisdiction under 35 U.S.C. § 6(b). We affirm the double patenting rejection, and reverse the rejection under§ 101. 1 Appellants identify the Real Party in Interest as Gamet BioTherapeutics, Inc. Appeal Br. 3. 2 An oral hearing was held on May 2, 2018. Appeal2016-007472 Application 11/797 ,322 BACKGROUND The Specification discloses a substantially homogeneous human cell population which co-expresses CD49c, CD90 and telomerase, but not CD34 or CD45. Spec. 11. Briefly, a "Primary Cell Bank" was generated by aspirating bone marrow cells from the iliac crest of healthy adult human volunteers; recovering a mononuclear cell fraction from the aspirate; seeding the mononuclear cell suspension in a tissue culture flask at a density of 50,000 cells/cm2, and incubating for 5 days at 37QC in an atmosphere consisting of 5% carbon dioxide, 5% oxygen, and 90% nitrogen/air; recovering adherent colony forming units (CPUs) and expanding the CPUs for an additional 3-5 days; and recovering and re-suspending adherent cells and freezing them for storage. More than 91 % of the adherent population was CD90 and CD49c positive. Id. at 21-24. A "Master Cell Bank" was generated by culturing an aliquot of cells from the Primary Cell Bank at a density of 30 cells/cm2 for two weeks at 37QC in an atmosphere consisting of 5% carbon dioxide, 5% oxygen, and 90% nitrogen/air. Id. "The purity of the cells (percentage of cells which co- express CD49c/CD90) in the Master Cell Bank was determined" and it was found to contain "a substantially homogenous population of adherent cells which co-express CD49c and CD90 and lack significant expression of the [myeloid-related] marker CD45." Id. at 24. In addition, the doubling rate of the cells from the Master Cell Bank "was 30 hrs and remained constant for at least 50 doublings." Id. at 25. "Even after 30 doublings, the population uniformly retained the characteristic morphology of small, dividing cells without apparent evidence 2 Appeal2016-007472 Application 11/797 ,322 of the enlarged, flat morphology of aged or terminally-differentiated cells." Id. Finally, the Specification teaches that "most human cells lack telomerase, [thus] telomeres shorten with each division until the cells growth arrest." Id. at 26. According to the Specification, however, "[c]ell populations which co-express CD49c and CD90 express telomerase at the level of approximately 13 transcripts/106 transcripts of 18S rRNA, which is consistent with the finding that this cell population continued to proliferate at a constant rate." Id. at 27. STATEMENT OF THE CASE Independent claim 133 and dependent claims 136-138 are on appeal. Claims 134 and 135, the only other claims pending, have been withdrawn from consideration. Appeal Br. 4. Claim 133 is representative and reads as follows: 133. An isolated cell population of human bone marrow- derived cells, wherein said cell population has been cultured in vitro at cell seeding densities of about 30 cells/cm2 under about 5% oxygen conditions for more than 30 population doublings, wherein said cell population continues to maintain a population doubling time of about 30 hours per doubling and wherein greater than 91 % of the cells in said cell population continue to co-express cell surface markers CD49c and CD90, and wherein said cell population does not express cell surface markers CD34 or CD45, and wherein said cell population expresses telomerase at a relative expression of between about 1 transcript of telomerase per 106 transcripts of an 18s rRNA and about 10 transcripts of telomerase per 106 transcripts of an 18s rRNA. Claims 133 and 136-138 stand rejected under the doctrine of obviousness-type double patenting, and under 35 U.S.C. § 101 as directed to patent patent-ineligible subject matter. 3 Appeal2016-007472 Application 11/797 ,322 DOUBLE PATENTING The Examiner provisionally rejected claims 133 and 136-138 on the ground of nonstatutory obviousness-type double patenting as unpatentable over claims 14, 21, 25, 26, and 97 of U.S. Application No. 09/960,244 (now US Patent No. 9,969,980), and claims 1-11, 57---60, and 63 of U.S. Application No. 10/251,685 (now US Patent No. 9,969,977). The patented claims, like the present claims, are directed to an isolated cell population derived from human bone marrow cells wherein greater than 91 % of the cell population co-expresses CD49c and CD90, and the cell population maintains a doubling rate of less than 30 hours after 30 cell doublings. Appellants have not addressed this rejection on the merits. See Appeal Br. 19. Accordingly, the rejection of claims 133 and 136-138 on the ground of obviousness-type double patenting is summarily affirmed. STATUTORY SUBJECT MATTER Claims 133 and 136-138 stand rejected under 35 U.S.C. § 101 as directed to patent-ineligible subject matter, specifically, a "product of nature" without "markedly different characteristics from what occurs in nature." Ans. 2, 3. Appellants contend that the Examiner's initial burden of establishing a prima facie case of lack of subject matter eligibility has not been met (Appeal Br. 6), and even if the Examiner's initial burden has been met, Appellants have provided evidence sufficient to rebut a prima facie case (id. at 10). The evidence relied on by Appellants includes the Declaration of Dr. Vanessa Ragaglia (signed October 29, 2014 ("Ragaglia Deel.")), explaining why "the claimed cell population is not a natural product, and is markedly different from what is found in nature" (Appeal Br. 10), as well as a number 4 Appeal2016-007472 Application 11/797 ,322 of references purporting to show that "culture conditions greatly affect the phenotype, i.e., structure, and behavior of a cell" (id. at 11 ). Dr. Ragaglia states that she is an expert in the field of "stem cells and cell biology, and mesenchymal stem cells in particular" (Ragaglia Deel. ,r 1 ), and provides evidence of this expertise (id., Appendix A). Principles of Law 35 U.S.C. § 101 states that"[ w ]hoever invents or discovers any new useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title." "Laws of nature, natural phenomena, and abstract ideas are not patentable." Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012) (citation omitted). The Supreme Court articulated a two-step test for patent eligibility under § 101 that "distinguish[ es] patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts." Alice Corp. Pty. Ltd. v. CLS Bank Int'!, 134 S.Ct. 2347, 2355 (2014) (citing Mayo, 132 S.Ct. at 1296-97). "First," Alice instructs us to "determine whether the claims at issue are directed to one of those patent-ineligible concepts." Id. (citation and quotations omitted). If the claims are directed to a patent ineligible concept then the court must proceed to the second step of the test-the "search for an inventive concept-i.e., an element or combination of elements that is sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the ineligible concept itself." Id. ( quotations and alterations omitted). 5 Appeal2016-007472 Application 11/797 ,322 When the invention is alleged to be a product of nature (i.e., a natural phenomenon), the patent-eligibility inquiry concerns whether the product is "new 'with markedly different characteristics'" than anything found in nature. Ass 'nfor Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 577, 590 (2013). Issue The issue raised by this rejection is whether the Examiner has established that the claimed cell population is patent ineligible because it is not markedly different from a progenitor cell population that exists in vivo. Findings of Fact (FF) The following findings of fact are pertinent to the issue raised by this appeal: FPL Javazon3 teaches that "ease of expansion in culture is one of the primary advantages of MSCs [mesenchymal stem cells], [but] it also may alter their fundamental nature." Javazon, 421, col. 1. "The cumulative data support a model of culture expansion altering the in vivo biology of the MSC in ways that may be detrimental to some clinical applications but perhaps are beneficial to others." Id. FF2. Zhang4 teaches that MSCs-a subpopulation of bone marrow derived stromal cells with the ability to differentiate into multiple cell types-are known to spontaneously differentiate and lose multipotency after 3 Elizabeth H. Javazon et al., Mesenchymal stem cells: Paradoxes of passaging, 32 EXPERIMENTAL HEMATOLOGY 414-425 (2004) ("Javazon") ( submitted by Appellants). 4 Douglas Zhang & Kristopher A. Kilian, The effect of mesenchymal stem cell shape on the maintenance of multipotency, 34 BIOMATERIALS 3962- 3969 (2013) ("Zhang") (submitted by Appellants). 6 Appeal2016-007472 Application 11/797 ,322 prolonged passaging ex vivo. Zhang, 3962, col. 2. However, Zhang teaches that certain cell culture conditions affect nmltipotency----e.g., confining MSCs to small islands on a patterned substrate, rather than a non-patterned substrate, enhances expression of mesenchymal stem cell markers and preserves the ability of the cells to differentiate into adipocytes and osteoblasts, even after the cells are released from the islands and reseeded. Id. at 3963, col. 1. FF3. Kiefer5 teaches that "supplements within a medium can greatly influence cellular phenotypes." Kiefer, Abstract. For example, Kiefer demonstrates that "cells cultured in BGM [basic cell growth medium] had efficient population doublings ... and retained ASC [adipose stem cell] markers CD44 and CD90, but had poor capacity to differentiate." Id. at 35. In contrast, KNAC [keratinocyte N acetyl-L-cysteine supplemented medium] and MAPC [ multipotent adult progenitor cell medium] cultured cells had longer doubling times but retained the capacity to differentiate into multiple lineages." Id. FF4. Bain6 teaches "[a]fter short-term expansion of MSCs from p3 to p5, chemotactic migration capacity decreased, whereas cell attachment rate increased." Bain, 163. In addition, "[c]ell functional characteristics ... are 5 Kristina M. Kiefer et al., The Influence of Culture Medium Type on Cellular Phenotype of Canine Adipose Derived Stem Cells, 3 OPEN JOURNAL OF REGENERATIVE MEDICINE 28-37 (2014) ("Kiefer") (submitted by Appellants). 6 Owen Bain et al., Altered hMSC functional characteristics in short-term culture and when placed in low oxygen environments: implications for cell retention at physiologic sites, 9 REGEN. MED. 153-165 (2014) ("Bain") ( submitted by Appellants). 7 Appeal2016-007472 Application 11/797 ,322 altered during short-term expansion and when moved from normoxic conditions typical of the bioprocess environment to reduced oxygen levels that reflect human injury sites." Id. Discussion The Examiner finds that the claimed cell population is "obtained from a naturally occurring human body," and "[t]here is no indication in the specification that the isolated cells have been modified by applicants or the claimed cells have any characteristics ( structural, functional or otherwise) that are markedly different from naturally occurring counterparts." Ans. 3. The Examiner acknowledges that "the claimed culture condition changes [the] phenotypes of the claimed cells," but contends that "[s]uch adjustment to their environment is due to the cells' innate or inherent property." Id. at 8. In the Examiner's view, "appellant's culturing procedure is not intended to produce the claimed cells with the claimed properties, rather appellant merely discovered the characteristics/properties of the cells after culturing the isolated cells under the claimed condition[ s]," thus, "the claimed feature[s] of the cells are independent from any effort of appellant." Id. at 6. Appellants contend that the Examiner has not identified a naturally occurring counterpart of the claimed cells; nor has the Examiner "provided any references showing that a cell population exists in vivo having the features of the claimed cell population." Appeal Br. 10. Moreover, Appellants note that claim 133's "culturing step recites that the cell population has been cultured in vitro at cell seeding densities of about 3 0 cells/cm2 under about 5% oxygen conditions for more than 30 population doublings," but contend that "[t]he Examiner has not established that the culturing aspect[s] of the claims are routine or conventional." Id. at 9. 8 Appeal2016-007472 Application 11/797 ,322 Appellants contend that the "characteristics of the claimed cells are the direct result of the inventor's experimentation with low oxygen and low density culture conditions." Reply Br. 4. Finally, Appellants have provided evidence purporting to establish that "[ c ]ulture conditions alter cell characteristics, such as phenotype (i.e., structure) and function" (Ragaglia Deel. ,r 6), and "the Office is incorrect in concluding that the cell population of claim 133 is a natural product that is not significantly different from a naturally occurring product" (id. ,r 5). In support of her position, Dr. Ragaglia cites multiple reports showing "the profound influence of culture conditions on the [MSC's] phenotype and behavior, and [that] once a cell is removed from its native environment, its phenotype and behavior are subject to change." Ragaglia Deel. ,r 17. For example, Dr. Ragaglia cites Javazon as teaching that discrepancies in the phenotypes of isolated and cultured MS Cs arise due in part to differences in isolation and culture conditions (id. ,r 11 ); Zhang as teaching that "MS Cs cultured without confinement have higher levels of osteogenic markers" (id. ,r 18); Kiefer as teaching that different culture media have different effects on cellular phenotype, doubling time, cytokine production, and ability to differentiate into stromal lineages (id. ,r 19); and Bain as teaching that even very brief culture can alter the attachment and chemotactic behavior of MSCs (id. ,r 10). See FFs 1--4. Finally, Dr. Ragaglia acknowledges that "an MSC is different and distinct from the cell population recited in claim 133" (id. ,r 7), but asserts that "[t]he conclusions regarding the structural differences between in vivo and in vitro MSCs can be extrapolated to the claimed cell population" (id. ,r 9). 9 Appeal2016-007472 Application 11/797 ,322 The Examiner dismissed the evidence discussed by Dr. Ragaglia- without addressing Dr. Ragaglia's assertion that differences between in vivo and in vitro MSCs can be extrapolated to the claimed cell population- because Appellants "did not establish that MSCs in vivo are [the] naturally occurring counterpart of the claimed cells, [thus] the feature of MSCs discussed cannot be considered as the characteristics of the naturally occurring counterpart of the claimed cells." Ans. 9. In our view, as with utility rejections under § 101, the Examiner has the initial burden of establishing that the claimed subject matter falls under a judicial exception to patent eligibility. See In re Swartz, 232 F.3d 862, 864 (Fed. Cir. 2000) (utility under 35 U.S.C. § 101). Assuming, for the purpose of deciding this appeal, that the Examiner's initial burden has been met, "the burden shifts to applicant to submit evidence sufficient to convince" one of ordinary skill in the art (id.) that the claimed subject matter is not directed to a judicial exception, i.e., a product of nature. Again, the relevant inquiry in this appeal is whether the claimed cell population is "new 'with markedly different characteristics"' from anything found in nature. Myriad, 569 U.S. at 590. As discussed above, Appellants provided rebuttal evidence in the form of "multiple reports ... show[ing] the profound influence of culture conditions on [a] cell's phenotype and behavior, and [that] once a cell is removed from its native environment, its phenotype and behavior are subject to change." Ragaglia Deel. ,r 17. The Examiner acknowledged that "the claimed culture condition changes [the] phenotypes of the claimed cells" (Ans. 8), but nevertheless maintained that "the claimed invention does not have markedly different characteristics from what occurs in nature" (id. at 3). The Examiner has not persuasively identified any inadequacy in 10 Appeal2016-007472 Application 11/797 ,322 Appellants' rebuttal evidence, nor has the Examiner provided scientific reasoning or evidence sufficient to support a finding that the claimed isolated cell population is a product of nature, lacking markedly different characteristics from a naturally occurring counterpart. Accordingly, we reverse the rejection of claims 133 and 136-138 under 35 U.S.C. § 101. SUMMARY The rejection of claims 133 and 136-138 under the doctrine of non- statutory obviousness-type double patenting is AFFIRMED. The rejection of claims 133 and 136-138 under 35 U.S.C. § 101 is REVERSED. 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 11 Copy with citationCopy as parenthetical citation