S-BIOMEDICS

Patent Trials and Appeals BoardDec 2, 2021

2021001633 (P.T.A.B. Dec. 2, 2021)

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. 15/322,003 12/23/2016 Dong Wook KIM 6680L-000190-US-NP 4900 28997 7590 12/02/2021 Harness Dickey (St. Louis) 7700 Bonhomme, Suite 400 St. Louis, MO 63105 EXAMINER FONTAINHAS, AURORA M ART UNIT PAPER NUMBER 1649 NOTIFICATION DATE DELIVERY MODE 12/02/2021 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): bkamer@hdp.com stldocket@hdp.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte DONG WOOK KIM and HAN SOO KIM Appeal 2021-001633 Application 15/322,003 Technology Center 1600 Before JEFFREY N. FREDMAN, JOHN E. SCHNEIDER, and RACHEL H. TOWNSEND, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 19, 21–23, 37, 39–41, and 43.2 We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies the real party in interest as S-Biomedics. Appeal Br. 3. 2 Claims 20, 25–32, 35, and 36 are pending in the application but have been withdrawn from consideration. Final Act. 2. Appeal 2021-001633 Application 15/322,003 2 CLAIMED SUBJECT MATTER The claims are directed to a method for treating ischemic diseases or neuroinflammatory diseases using neural progenitor cells. Claim 19, reproduced below, is illustrative of the claimed subject matter: 19. A method for treating stroke the method comprising administering a composition comprising poly-sialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells as an active ingredient to a subject in need thereof, wherein the PSA-NCAM-positive neural precursor cells are separated from neural rosettes differentiated from pluripotent stem cells, using an anti-PSA-NCAM-antibody, and wherein the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells (IPSCs). REFERENCES The prior art relied upon by the Examiner is: Name Reference Date Dae-Sung Kim et al., Highly Pure and Expandable PSA-NCAM-Positive Neural Precursors from Human ESC and iPSC-Derived Neural Rosettes, 7 PLoS ONE e39715 (2012) Serena Barral et al., Efficient neuronal in vitro and in vivo differentiation after immunomagnetic purification of mESC derived neuronal precursors, 10 Stem Cell Res. 133–146 (2013) Da-Jeong Chang et al., Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke, 22 Cell Transplantation 1427–1440 (2013) REJECTION The Examiner has rejected claims 19, 21–23, 37, 39–41, and 43 under 35 U.S.C. § 103 as unpatentable over Chang in view of Kim and Barral. Appeal 2021-001633 Application 15/322,003 3 OPINION Issue The issue with respect to this rejection is whether a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 19, 21–23, 37, 39–41, and 43 would have been obvious to one of ordinary skill in the art at the time the invention was made over Chang in combination with Kim and Barral. The Examiner finds Chang teaches transplanting stem-cell derived neural precursor cells (“NPCs”) to restore neural tissues and circuitry thereby treating stroke. Final Act. 3–4. The Examiner finds Chang teaches that the NPCs are obtained from induced pluripotent stem cells which include embryonic stem cells that were isolated from rosette-like structures. Id. at 4. The Examiner finds Chang teaches that transplantation of NPCs promotes angiogenesis. Id. The Examiner finds Chang teaches looking to PSA-NCAM marker as a way to identify endogenous neurogenesis and cell migration in the SVZ of stroke induce brain (see page 1438, 2nd column, 1st paragraph, page 1436, bottom of 1st column and top of 2nd column) but does not teach using PSA-NCAM positive NPCs as required in instant claims 19 and new claim 43. Id. The Examiner finds Kim teaches producing PSA-NCAM positive NPCs from human pluripotent stem cells for replacement therapies of the nervous system. Id. at 5. The Examiner finds “Kim teaches using a PSA- NCAM antibody to isolate PSA-NCAM positive cells from expanded neuronal rosettes cells.” Id. The Examiner finds “Kim teaches that the PSA- NCAM positive NPCs are able to integrate into the adult mammalian brain, Appeal 2021-001633 Application 15/322,003 4 have full capacity of neural differentiation potential in vivo and have a significantly lower possibility of neural outgrowth when compare[d] to unsorted and non-propagated neural rosette cells.” Id. The Examiner finds “Kim teaches using these PSA-NCAM positive NPCs as reliable cell source for future cell replacement therapy. Kim does not specifically teach using these specific cells for the treatment of ischemic stroke.” Id. The Examiner finds Barral teaches a method for isolating PSA- NCAM positive NPCs from embryonic stem cells and derived pluripotent cells (iPSCs) and their use for transplantation and cell replacement therapy. Id. at 6. The Examiner finds Barral teaches “using PSA-NCAM antibodies to help identify and isolate the PSA-NCAM positive cells.” Id. The Examiner finds Barral “teaches that these PSA-NCAM cells have the potential for promoting brain repair such as lesion models of ischemia and brain trauma and teaches the administration of these sorted cells into the forebrain.” Id. The Examiner concludes It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Chang, Kim and Barral. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because one of ordinary skill in the art would want to administer a cell population able to produce neuronal cells to replace the lost cells due to ischemic stroke without fear of leading to unwanted tumorigenesis. Chang teaches that one of the issues with NPCs is the potential of tumorigenesis (see page 1433, 1st column, 2nd paragraph) as does Kim (see page 2, 1st column) and Barral (see page 143, 1st column). Further, one would be motivated to use the cells taught by Kim and Barral in the method of treatment for ischemic stroke taught by Chang since these cells are capable of integrating into the cortex and produce neurons as taught by Barral (see page 140, 2nd column, 2nd paragraph). One of Appeal 2021-001633 Application 15/322,003 5 ordinary skill would be motivated to use these PSA-NCAM positive cells to treat cerebrovascular ischemic injury such as stroke as taught by Chang since Barral teaches that these PSA- NCAM cells have the potential for promoting brain repair such as lesion models of ischemia and brain trauma and teaches the administration of these sorted cells into the forebrain (see page 134, 2nd column, 1st paragraph and 2nd paragraph). Further, one of ordinary skill in the art would be motivated to administer the sorted PSA-NCAM cells to infarct site as in instant claim 39 since one would want to administer the treatment of replacement cells close to the area of cell loss to reduce the amount of migration necessary to reach the site of injury and Barral has already shown that these presorted cell are capable of integrating into the cortex/forebrain of an animal model. Finally, one of ordinary skill in the art would have a reasonable expectation of increasing vascularization at the site of the lesion in a stroke patient since NPCs also promotes angiogenesis (see page 1438, 1st column, bottom of 1st paragraph). Accordingly, the cumulative reference teachings render obvious the claimed method. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Id. at 7–8. Appellant contends that while Chang teaches that the NPCs used have a therapeutic potential, the equivocal language of Chang does not specifically teach that the NPCs can be used to treat stroke. Appeal Br. 6. Appellant also contends that Chang uses different NPCs than those claimed. Id. Appellant contends that Barral also does not teach or suggest using NPCs to treat stroke let alone the use of PSA-NCAM-positive NPCs to treat stroke. Id. With respect to claim 43, Appellant contends that Chang suggests the NPCs can promote angiogenesis but that angiogenesis is not the same as Appeal 2021-001633 Application 15/322,003 6 vascularization as recited in claim 43. Id. at 7. Appellant argues that the Examiner has improperly equated angiogenesis with vascularization and has arrived at an improper finding of obviousness. Id. Appellant contends that one skilled in the art would not have a reasonable expectation of success in combining the references as neither Chang nor Barral shows any likelihood that PSA-NCAM-positive NPCs can be used to treat stroke. Id. Appellant contends that there is no motivation to combine the teachings of Chang and Kim. Id. at 8. Appellant argues that the references offer no guidance as to why one skilled in the art would replace the NPCs of Chang with the NPCs of Kim. Id. Appellant contends that the Examiner has not set forth a sufficient justification for modifying the method of Chang to use the cells of Kim. Id. Finally, Appellant contends that the rejection is based on the impermissible use of hindsight. Id. at 9. Appellant contends that none of the references teach or suggest the use of PSA-NCAM-positive NPCs to treat stoke and only by using the present Specification as a road map would one skilled in the art arrive at the presently claimed invention. Id. at 9–10. Principles of Law “[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). “The factual predicates underlying an obviousness determination include the scope and content of the prior art, the differences between the Appeal 2021-001633 Application 15/322,003 7 prior art and the claimed invention, and the level of ordinary skill in the art.” In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998). Analysis We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions set out in the Final Action and Answer regarding this rejection. We find the Examiner has established a prima facie showing that the subject matter of the claims would have been obvious over Chang combined with Kim and Barral to a person of ordinary skill in the art at the time the invention was made. Appellant has not produced evidence showing, or persuasively argued, that the Examiner’s determinations on obviousness are incorrect. Only those arguments made by Appellant in the brief have been considered in this Decision. Arguments not presented in the brief are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015). We have identified claim 19 as representative; therefore, all claims, except for claim 43 which was argued separately, fall with claim 19. We address Appellant’s arguments below. Appellant contends that Chang does not teach or suggest the use of NPCs to treat stroke but only states that work provides encouraging evidence of potential therapeutic value. Appeal Br. 6. Appellant also contends that Chang suggests the use of cells different than those recited in the claims. Id. We are not persuaded by these arguments. We agree with the Examiner that Chang clearly teaches the use of NPCs to treat stroke. Ans. 8. Chang states “[o]ur results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.” Chang Abstr. Chang also states that the study of the rodent model of middle cerebral artery occlusion model studied where iPSC-derived NPCs were Appeal 2021-001633 Application 15/322,003 8 implanted, demonstrated that iPSC-derived NPCs “show significant reduction in inflammation, gliosis, and apoptosis, as well as significant contribution to the endogenous neurogenesis, implying that iPSC-derived NPCs have the unique properties of treating stroke using all the several modes of action as described above.” Chang 1428. With respect to Chang using different cells than those recited in the claims, the Examiner noted this difference and cites to Kim for teaching the use of PSA-NCAM-positive NPCs. Final Act. 4–5. Appellant’s argument is an attack on the teachings of the individual reference and fails to address the combined teachings of the references. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellant contends that Barral also does not suggest the clinical use of NPCs to treat stroke. Appeal Br. 7. Appellant contends that Barral suggests that if NPCs could be used in humans, it might represent a preferred strategy for exploring future therapeutic applications. Id. Appellant contends that Barral’s equivocal statements would not lead one skilled in the art to the claimed invention. Id. We remain unpersuaded by Appellant’s argument. As discussed above, Chang teaches the use of NPCs to treat stroke. It is the combined teaching of the references that serves as the basis of the rejection, not the individual references. Appeal 2021-001633 Application 15/322,003 9 Appellant contends that one skilled in the art would not have a reasonable expectation of success as the Examiner mischaracterizes the teachings of Chang and Barral. Appeal Br. 7. Appellant contends that the Examiner improperly transitions from the preclinical experiments reported in the references to an expectation of success without presenting any guidance from the art or additional reasoning. Id. In support of this argument Appellant cites to OSI Pharmaceuticals v. Apotex Inc., 939 F.3d 1375, 1384 (Fed. Cir. 2019) where our reviewing court found the disclosure of an antibody, in the absence of any clinical, preclinical animal, or preclinical in vitro data of the antibody’s effect on lung cancer, did not render a method of using the antibody to treat lung cancer obvious. Id. We have considered Appellant’s argument and are not persuaded that the rejection is in error. The present claims only call for the treatment of stroke, and are not limited to treatment of humans. Appeal Br. 12 (Claims App.). Chang states the transplantation of the NPCs in animals showed “significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis.” Chang Abstr. Thus, Chang presents animal data to support the conclusion that NPCs are effective for the treatment of stroke. The facts in the present case are distinguishable from those in OSI. In OSI, the reference relied on failed “to disclose any in vitro or in vivo efficacy data for erlotinib or otherwise suggest the use of erlotinib to treat NSCLC.” OSI, 939 F.3d at 1384. This is in direct contrast to the present case where Chang provides in vivo animal data showing the efficacy of NPCs to treat stroke. Chang Abstr.; 1433–1438. Chang’s animal data in a relevant animal model would have provided one of ordinary skill in the art with a reason to Appeal 2021-001633 Application 15/322,003 10 expect to be able to treat stroke. Cf. Edwards Lifesciences AG v. CoreValve, Inc., 699 F.3d 1305, 1309 (Fed. Cir. 2012) ( “[I]t has long been recognized that when experimentation on human subjects is inappropriate, as in the testing and development of drugs and medical devices, the enablement requirement may be met by animal tests or in vitro data.”) Appellant contends that the Examiner has failed to adequately set forth a motivation to modify the teachings of Chang with those of Kim. Appellant contends that while the references teach that the NPCs of Kim can be readily integrated into the cortex and produce neurons, that is insufficient to lead one skilled in the art to use the NPCs of Kim in the method of Chang let alone to treat stroke. Appeal Br. 8–9. This argument is also unpersuasive. Kim teaches that the technique disclosed therein “suggests that PSA- NCAM-targeted cell isolation enables enrichment of a homogenous population of primitive NPCs from hPSCs and minimizes safety concerns after transplantation. This provides a promising cell source for practical applications, such as drug screening and regenerative medicine for central nervous system (CNS) diseases.” Kim 2. Barral teaches that PSA-NCAM cells have the potential for promoting brain repair such as lesion models of ischemia and brain trauma and teaches the administration of these sorted cells into the forebrain. Barral 134. Chang teaches that NPCs can be effective in treating stroke. We find that the combined teachings of the references would have motivated one skilled in the art to use the NPCs of Kim in the method of Chang given Kim’s teaching of a homogenous population of NPCs that have minimal safety concerns. Appellant contends that the rejection relies on the improper use of hindsight in that the teachings of Chang and Barral are speculative regarding Appeal 2021-001633 Application 15/322,003 11 the clinical usefulness of NPCs and Kim is silent with respect to any clinical effect. Appeal Br. 9–10. Appellant contends that only using the present Specification as a guide would one skilled in the art combine the teachings of the references to produce the claimed invention. Id. We have considered Appellant’s argument and are not persuaded that the Examiner resorted to the improper use of hindsight. “Any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). In the present case, Chang specifically teaches the use of NPCs to treat stroke. Chang Abstr. Kim teaches the advantages of using PSA- NCAM-positive NPCs and that they can be used as “regenerative medicine for central nervous system (CNS) diseases.” Kim 2. Thus, the references themselves suggest the use of the NPCs of Kim in the method of Chang to treat stroke. Appellant does not point to nor do we discern any specific knowledge that is gleaned only from Appellant’s disclosure. Finally, with respect to claim 43, Appellant contends that the Examiner improperly equates angiogenesis with vascularization. Appeal Br. 7. Appellant contends that vascularization and angiogenesis are two different process with angiogenesis focused on the protrusion of and outgrowth of capillaries whereas vascularization is directed to formation of new blood vessels. Id. Appellant contends that Chang only teaches the use of NPCs to stimulate angiogenesis and not vascularization as recited in claim 43. Appeal 2021-001633 Application 15/322,003 12 Again, we find this argument unpersuasive. As the Examiner points out, Appellant offers no evidence to support its contention that angiogenesis and vascularization are separate processes but only offers attorney argument. Ans. 10. “Attorney’s argument in a brief cannot take the place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Conclusion Based on the foregoing we conclude that a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 19, 21–23, 37, 39–41, and 43 would have been obvious to one of ordinary skill in the art at the time the invention was made over Chang in combination with Kim and Barral. CONCLUSION The Examiner’s rejection is affirmed. More specifically, the rejection of claims 19, 21–23, 37, 39–41, and 43 under 35 U.S.C. § 103 as unpatentable over Chang in view of Kim and Barral is affirmed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 19, 21–23, 37, 39–41, 43 103 Chang, Kim, Barral 19, 21–23, 37, 39–41, 43 Appeal 2021-001633 Application 15/322,003 13 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED