STEMBIOSYS, INC.

Patent Trials and Appeals BoardOct 26, 2021

2021000086 (P.T.A.B. Oct. 26, 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. 15/521,970 04/26/2017 Rogelio ZAMILPA STEM.P0002US/100033869 1001 32425 7590 10/26/2021 NORTON ROSE FULBRIGHT US LLP 98 SAN JACINTO BOULEVARD SUITE 1100 AUSTIN, TX 78701-4255 EXAMINER PYLA, EVELYN Y ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 10/26/2021 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): aoipdocket@nortonrosefulbright.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ROGELIO ZAMILPA and EDWARD S. GRIFFEY Appeal 2021-000086 Application 15/521,970 Technology Center 1600 Before JOHN E. SCHNEIDER, DEBRA L. DENNETT, 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 1–4, 7, 8, 11, 13, 17, 18, and 23–26. We have jurisdiction under 35 U.S.C. § 6(b). We reverse and enter new grounds of rejection. 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 StemBioSys, Inc. Appeal Br. 1. Appeal 2021-000086 Application 15/521,970 2 CLAIMED SUBJECT MATTER “Mesenchymal stem cells (MSCs) are multipotent cells that can produce daughter stem cells and can also differentiate into a variety of cell types.” Spec. ¶ 3. “However, MSCs tend to lose their stem cell properties under conventional cell culture conditions, such as when cultured on tissue culture plastic.” Id. The invention relates to using “bone marrow stromal cell derived extracellular matrix coated microcarriers as an in-vitro microenvironment for the maintenance and expansion of mesenchymal stem cells in an undifferentiated state.” Id. ¶ 2. Claim 1, reproduced below, is illustrative of the claimed subject matter: 1. A method of maintaining and expanding mammalian mesenchymal stem cells in culture in an undifferentiated state, the method comprising: a. producing a 3D extracellular matrix coating on the surface of microcarriers comprising: i. adding the microcarriers to a culture medium; ii. adding mammalian bone marrow stromal cells to the culture medium; iii. culturing the bone marrow stromal cells to produce the 3D extracellular matrix coating on the surface of the microcarriers; iv. decellularizing the extracellular matrix coated microcarriers of the bone marrow stromal cells; and b. culturing the mammalian mesenchymal stem cells in the presence of the extracellular matrix coated microcarriers; wherein the extracellular matrix coating restrains differentiation of the mammalian mesenchymal stem cells; and wherein the microcarriers are spherical in shape or are hollow fibers. Appeal 2021-000086 Application 15/521,970 3 REFERENCES The prior art relied upon by the Examiner is: Name Reference Date Antebi Ben Antebi et al., Stomal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity if Mesenchymal Stem Cells on Three- Dimensional Scaffolds, 21 Tissue Eng’g 171–81 2015 Goh Tony Kwang-Poh Goh et al., Microcarrier Culture for Efficient Expansion and Osteogenic Differentiation of Human Fetal Mesenchymal Stem Cells, 2 Bioresearch Open Access 84–97 2013 REJECTIONS The Examiner has rejected the claims as follows: Claims 1–4, 7, 8, and 23–26 have been rejected under 35 U.S.C. § 102 as anticipated by Antebi. Claims 17 and 18 have been rejected under 35 U.S.C. § 103 as unpatentable over Antebi. Claims 11 and 13 have been rejected under 35 U.S.C. § 103 as unpatentable over Antebi in view of Goh. OPINION Anticipation by Antebi The issue with respect to this rejection is whether a preponderance of the evidence supports the Examiner’s conclusion that claims 1–4, 7, 8, and 23–26 are anticipated by Antebi. The Examiner finds Antebi discloses “culturing mesenchymal stem cells (MSCs) on three-dimensional scaffolds that comprise stromal-cell- Appeal 2021-000086 Application 15/521,970 4 derived extracellular matrix (ECM).” Final Act. 3. The Examiner finds Antebi discloses the use of disc shaped microcarriers comprising “collagen/hydroxyapatite (Col/HA) scaffolds.” Id. The Examiner finds Antebi discloses that the scaffolds are then seeded with “adherent bone marrow mesenchymal stem cells (MSCs)” and then incubated for an hour to allow the cells to attach. Id. The Examiner finds Antebi discloses that the scaffolds are then “transferred to 6-well culture plates and cultured for 21 days to promote deposition of stromal-cell ECM.” Id. The Examiner finds that Antebi teaches that the method described inherently produces an extracellular matrix that restrains differentiation of the mesenchymal stem cells in that the stromal-cell-derived ECM retains stemness. Id. at 4. Appellant contends that Antebi does not anticipate claims 1–4, 7, 8, and 23–26 because the microcarriers are not spherical in shape but are discs. Appeal Br. 3. Appellant contends that the Examiner has improperly found that the microcarriers of Antebi are discoid in shape and that is the same as spherical. Id. Appellant points out that Antebi describes the microcarriers as discs that are 1 cm in diameter and 1.5 mm in thickness. Id. Appellant contends that these dimensions describe a microcarrier that is clearly not spherical. Id. We have considered the arguments presented by the Examiner and Appellant as well as the evidence of record and find that Appellant has the better argument. While the Specification does not explicitly define the term spherical, the Specification does state: “The microcarriers can be in any shape including, but not limited to spherical (beads) and cylindrical shapes.” Spec. ¶ 55. Thus, the Specification teaches that the term spherical which the Appeal 2021-000086 Application 15/521,970 5 Specification identifies to include beads is different from the term cylindrical. A sphere has the same diameter in the x, y, and z direction. A cylinder, on the other hand, does not. . Antebi clearly describes the microcarriers as discs having a diameter almost ten times the thickness of the disc. We agree with Appellant that the Examiner’s proposed definition of spherical that embraces discs is unreasonable and unsupported by the evidence. Appeal Br. 3. The Obviousness Rejections Both of the obviousness rejections rely on the same teachings of Antebi as the anticipation grounds. Final Act. 7–8. As discussed above, we find that Antebi does not anticipate the claims, as Antebi does not teach a spherical microcarrier. For this same reason the rejections for obviousness must also fail. New Grounds of Rejection – Obviousness based on Antebi and Goh We enter a new ground of rejection for claims 1–4, 7, 8, 11, 13, 17, 18, and 23–26. We reject the pending claims under 35 U.S.C. § 103 as unpatentable over Antebi in view of Goh. While we agree with Appellant that claims 1–4, 7, 8, and 23–26 are not anticipated by Antebi, we find that the claims are unpatentable under 35 U.S.C. § 103 as obvious over Antebi in view of Goh. As discussed above, Antebi teaches all of the limitations of the claims with the exception of the requirement that the microcarriers are spherical in shape or are hollow fibers. Goh teaches several different microcarriers for growing MSCs that are spherical in shape. Goh, 87–88, Table 1. Given that the microcarriers in both Antebi and Goh are used to grow MSCs, we find that it would have been obvious to one skilled in the art to modify the microcarrier of Antebi to Appeal 2021-000086 Application 15/521,970 6 be spherical in shape. It is obvious to those skilled in the art to substitute one known equivalent for another. See In re Omeprazole Patent Litig., 483 F.3d 1364, 1374 (Fed. Cir. 2007) (“[T]his court finds no . . . error in [the] conclusion that it would have been obvious to one skilled in the art to substitute one ARC [alkaline reactive compound] for another.”). With respect to claims 17 and 18, we agree with the Examiner that “Antebi discloses culturing in a standard cell-culture incubator at an incubation temperature of 37°C. Given that Antebi does not teach an absence of oxygen or hypoxic conditions, it is considered that Antebi employs standard, normoxic culture conditions, absent evidence to the contrary.” Final Act. 7. Again, Antebi teaches or suggests all of the limitations of the claims with the exception of the microcarrier being spherical. Goh teaches this limitation. Turning to claims 11 and 13, we agree with the Examiner that Antebi teaches all of the limitation of these claims with the exception of the limitation that the microcarrier has a positive charge or are composed of cross-linked dextran matrix. Final Act. 8. Goh, however, in addition to teaching spherical microcarriers, also teaches using microcarriers comprised of Cytodex-3, a positively charged cross-linked dextran matrix. Goh, 86, Table 1; Spec. ¶ 56. We find that it would have been prima facie obvious to one having ordinary skill in the art at the time of filing to substitute the spherical Cytodex-3 microcarriers, as taught by Goh, as the MSC microcarriers in the method of Antebi for the predictable result of successfully providing a three-dimensional scaffold for expansion of MSCs. It is obvious to those skilled in the art to substitute one Appeal 2021-000086 Application 15/521,970 7 known equivalent for another. See In re Omeprazole Patent Litig., 483 F.3d at 1374. Appellant contends that one skilled in the art would not substitute the Cytodex microcarriers of Goh for the substrate used in Antebi as it would render Antebi unsuitable for its intended purpose and change the principle of operation. Appeal Br. 4. Appellant contends that Antebi teaches that the key to the Antebi process being able to reduce the loss of stemness is the use of a 3D Col/HA scaffold and the formation of an ECM within the 3D scaffold. Id. at 4–5. Appellant contends that substitution of the Cytodex microcarriers would present only a 2D surface for cell growth not a 3D structure. Id. at 5–6. Appellant contends that the structure of the scaffold in Antebi mimics native tissue with its 3D interconnected pore structure, high degree of porosity, its biocompatibility and its natural collagen. Id. at 6. Appellant contends “[s]ubstituting Cytodex beads, which do not have similar properties and provide only the bead surface for growth, would thus frustrate Antebi's purpose of providing a scaffold that mimics native tissue.” Id. We are not persuaded by Appellant’s arguments. We begin by noting that Goh teaches that the microcarriers produce a 3D macroporous scaffold structure. See Goh, Abstr. Thus, contrary to Appellant’s contention, Goh teaches a 3D scaffold. We agree with the Examiner that Goh has shown it was well known in the art to employ spherically shaped cross-linked dextran matrix microcarriers (three-dimensional scaffold) for the successful culture and expansion of mesenchymal stem cells (MSCs), for subsequent osteogenic differentiation (Goh’s Abstract and Table 1, page 86). Antebi is likewise employing 3D scaffolds for promoting expansion of mesenchymal stem cells and retaining the Appeal 2021-000086 Application 15/521,970 8 osteogenic differentiation capacity. Given that Goh has shown the Cytodex-3 microcarriers are successfully employed for expansion of the mesenchymal stem cells (Abstract) one would have had a reasonable expectation of successfully substituting Cytodex-3 microcarriers for the expansion of the MSCs in the method of Antebi. Goh has established the microcarrier scaffold has the similar property of MSC expansion for subsequent osteogenic differentiation. Thus, the culture scaffolds of Goh and Antebi share the same utility and the similar property of MSC expansion for subsequent osteogenic differentiation. The culture scaffolds of Goh and Antebi are known in the field for successful MSC expansion, and subsequent osteogenic differentiation. As previously set forth in the final Office action, substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395. Ans. 9. CONCLUSION The Examiner’s rejections are reversed. A new ground of rejection is entered. More specifically, The rejection of claims 1–4, 7, 8, and 23–26 under 35 U.S.C. § 102 as anticipated by Antebi is reversed. The rejection of claims 17 and 18 under 35 U.S.C. § 103 as unpatentable over Antebi is reversed. The rejection of claims 11 and 13 under 35 U.S.C. § 103 as unpatentable over Antebi in view of Goh is reversed. A new rejection of claims 1–4, 7, 8, 11, 13, 17, 18, and 23–26 under 35 U.S.C. § 103 as unpatentable over Antebi in view of Goh is entered. Appeal 2021-000086 Application 15/521,970 9 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/ Basis Affirmed Reversed New Ground 1–4, 7, 8, 23–26 102 Antebi 1–4, 7, 8, 23–26 17, 18 103 Antebi 17, 18 11, 13 103 Antebi, Goh 11, 13 1–4, 7, 8, 11, 13, 17, 18, 23–26 103 Antebi, Goh 1–4, 7, 8, 11, 13, 17, 18, 23–26 Overall Outcome 1–4, 7, 8, 11, 13, 17, 18, 23–26 1–4, 7, 8, 11, 13, 17, 18, 23–26 Appeal 2021-000086 Application 15/521,970 10 TIME PERIOD FOR RESPONSE This Decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides that “[a] new ground of rejection . . . shall not be considered final for judicial review.” 37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO MONTHS FROM THE DATE OF THE DECISION, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new evidence relating to the claims so rejected, or both, and have the matter reconsidered by the examiner, in which event the prosecution will be remanded to the examiner.… (2) Request rehearing. Request that the proceeding be reheard under § 41.52 by the Board upon the same record…. Further guidance on responding to a new ground of rejection can be found in the Manual of Patent Examining Procedure § 1214.01. REVERSED; 37 C.F.R. § 41.50(b)