DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 26-46), and the species of a porous mesh backing (claims 28, 40, and 45) in the reply filed on September 25, 2025 is acknowledged. The traversal is on the ground(s) that there is no serious burden to examine all the species together. (Remarks, 2, September 25, 2025.) In view of Mooney (cited below), the restriction requirement is hereby withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 26-28, 30, 32-43, 47, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Mooney (US 2008/0044900).
Mooney teaches a patch graft or scaffold composition and a bioactive composition incorporated into or coated onto the scaffold composition for cell transplantation or graft (title; abstract; paras.0004-07, 0011, 0013-17, 0022, 0051, 0055, 0063, 0069, 0107, 0127, 0134). “The biocompatible scaffolds of the invention are useful in a broad range of in vivo and in vitro regenerative medicine and tissue engineering” (para. 0092; paras.0019, 0022), including as liver scaffolds and for “liver tissue regeneration” comprising hepatocyte growth factor (paras.0017, 0044, 0082, 0088). Official notice is taken that liver cancer, nonalcoholic fatty liver disease, and hepatitis among others in claim 27 are well-known and long-studied diseases of the liver. The “scaffold or scaffold device is the physical structure upon which or into which cells associate or attach” (para.0049; see para. 0132), and comprises a “biocompatible polymer matrix” such as a hydrogel of hyaluronic acid (paras.0049, 0051-52). The scaffold “incorporates or is coated with a bioactive composition including hyaluronic acid (paras.0006, 0052), and comprises “physical channels or paths through which cells can move more easily towards a targeted area of egress” (para. 0006).
Mooney teaches seeding the scaffold “with two or more substantially pure populations of cells” (para.0041), of the cell types recited in claims 34-39 (paras.0017, 0042, 0044, 0046), i.e., “[d]ifferent cell types, e.g., stem vs. differentiated,…optionally vary in phenotype, e.g., differentiation state, activation state,…[s]uch cells include but are not limited to, various stem cell populations (embryonic stem cells differentiated into various cell types), …mesenchymal stem cells, …epithelial cells,…” (para. 0044). Applicant discloses the “early lineage stage mesenchymal cells (ELSMCs) appropriate for patch grafts can be angioblasts, …, early stage stellate cells, or mesenchymal stem cells (MSCs), or mixtures of these.” (para.0137, pre-grant publication US 2018/0361027). The cells may be autologous or allogenic cells (para.0092), genetically modified (para. 0045), with maintained “stemness” (para. 0068), i.e., in a suitable medium.
Regarding “viscoelasticity sufficient to allow for migration …subject’s liver” in claim 26, limitation (a), Mooney teaches, “scaffold composition and/or bioactive composition temporally and spatially (directionally) controls egress of a resident cell or progeny thereof” (abstract; paras. 0004, 0127, 0154 “…allow the physical contact required for cells to migrate out of the device into the wound”).
Mooney further teaches scaffolds comprise multiple compositions and one or more layers (paras.0006, 0017, 0018, 0044, 0048, 0067, 0069-0071). One layer comprises a biocompatible, biodegradable material having a viscoelasticity sufficient to inhibit (or provide a barrier to) migration of said cell population in a direction of said backing: "[f]or example, the scaffold composition is differentially permeable, allowing cell egress only in certain physical areas of the scaffold… by selecting or engineering a material for greater or smaller pore size ... or viscoelasticity" (para. 0006, emphases added). Cell egress in “only”, i.e., limited, areas of the scaffold indicates non-egress in the other areas. Suitable scaffold compositions include polymers such as silk (para.0013).
Regarding claim 26, limitation “(b) a backing…having a viscoelasticity sufficient to inhibit a migration…away from the target tissue”, and claims 28,
Mooney teaches a “semipermeable outer surface is provided by either using a composite material (e.g., nonporous silicone sheet placed on outer surface of porous device) or processing the device to create anisotropic porosity” (para.0154). As noted above, Mooney teaches the scaffold “incorporates or is coated with a bioactive composition including hyaluronic acid (paras.0006, 00490052) and therefore a skilled person would have understood that the outer surface may comprise a hydrogel for its benefits including an adjustable level of consistency, hydration, and/or porosity (para.0049).
Regarding claim 43, Mooney discloses hydrogel “to conform to the wound and provide control over fluid transport, prevent infection, and allow the physical contact required for cells to migrate out of the device into the wound”, i.e., the treatment site (para. 0154; see paras. 0006, 0049).
Mooney does not teach an example wherein the specific patch graft embodiment precisely as recited in claim 26 was contacted with the liver of a subject’s to treat the subject’s liver disease or disorder. However it would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to do so. The skilled person would have been motivated to do so because Mooney expressly teaches a scaffold coated with hyaluronic acid (paras.0006, 0052), “with two or more substantially pure populations of cells” (para.0041), e.g., “hepatocytes for liver tissue regeneration, repair or organ transplantation” (para.0017; see paras.0017, 0042, 0044, 0046), and comprises “physical channels or paths through which cells can move more easily towards a targeted area of egress” (para. 0006). The “scaffold composition and/or bioactive composition temporally and spatially (directionally) controls egress of a resident cell or progeny thereof” (abstract; paras. 0004, 0154 “…allow the physical contact required for cells to migrate out of the device into the wound”). Furthermore the scaffold comprises multiple layers (paras.0006, 0017, 0018, 0044, 0048, 0067, 0069-0071), including one having a viscoelasticity sufficient to inhibit (or provide a barrier to) migration of said cell population in a direction of said backing: "[f]or example, the scaffold composition is differentially permeable, allowing cell egress only in certain physical areas of the scaffold… by selecting or engineering a material for greater or smaller pore size ... or viscoelasticity" (para. 0006, emphases added). In other words Mooney teaches each of the specific limitations in claim 26.
Claims 26-48 are rejected under 35 U.S.C. 103 as being unpatentable over Mooney (US 2008/0044900) in view of Turner (US 2011/0274666) and Ghosh (Ghosh, K., et al., Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties, Biomaterials 28 (2007) 671-679).
Mooney does not specifically teach the third hydrogel overlaid on a serosal surface of the backing or migration-inhibiting layer or the viscoelasticity recited in claims 29, 31, and 44-46.
Turner teaches methods of repairing diseased or dysfunctional organs, including kidney, through “engraftment of cells from healthy tissue … admixed with gel-forming biomaterials and nutrient medium, signaling molecules and extracellular matrix components that can be made insoluble rapidly upon transplantation to form a graft” (abstract; see entire document, including title; Fig. 1 and accompanying text; paras.0007, 0011-13, 0036, 0052-61, 0064-80, 0084). The cells are delivered in “scaffolds that can be localized to the diseased tissue to promote necessary proliferation and engraftment” (para.0033; see para.0057). “Hyaluronans are one of the preferred materials.” (Para.0007; see paras. 0012-13). A graft “may be designed for placement onto the surface of an organ or tissue, in which case the graft would be held in place with a biocompatible and biodegradable covering (‘band aid’)” (para.0084, emphasis added; see paras.0008, 0015; claims 1-3, 19, 21-23, 28-29, 32-37, 39; Fig.1). Such covering comprises a “backing” to the scaffold.
Turner specifically teaches viscoelastic properties of its scaffolds, including “the insoluble complex of cells and biomaterials possesses a viscosity ranging from about 0.1 to about 100 kPa, …, and most preferably a stiffness from about 11 to about 3500 Pa” (para.0012, see paras.0016, 0087). “[T]he stiffness, viscoelastic properties and viscosity of KM-HA [Kubota’s medium-hyaluronic acid] hydrogels can depend on CMHA-S and PEGDA content. …These KM-HA hydrogels can yield shear moduli ranging from 11 to 3500 Pa with different PEGDA and CMHA-S concentrations when mixed in buffered distilled water, but these values can be modulated by using diverse basal medium like Kubota’s medium” (paras.0086, 0121; see Fig.4, paras. 0018, 0090 ). Turner claims a “tissue graft comprising cells admixed with one or more biomaterials to form a graft, wherein the components of the graft have a shear moduli ranging from 25 to 520 Pa” (claim 28).
Ghosh examines the effects of viscoelastic properties of hyaluronan/fibronectin hydrogels on cell behavior (Abstract). Ghosh discloses preparing hydrogels with viscoelasticity of 95, 550 and 4270 Pa and seeding human dermal fibroblasts (hDFs) on the hydrogels (Section 2.1,2.4). hDF migration speed significantly decreased as viscosity of the hydrogel increased (Section 3.3.1, Fig. 5). Ghosh suggests that softer hydrogels (e.g., 95 Pa) may be utilized to promote cellular migration, while viscosities of 550 Pa or higher promote cellular adhesion and proliferation (Section 3.3.1,4, Fig. 5).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Mooney, Turner, and Ghosh and treat a liver disease or disorder by providing cell populations on a scaffold composition having a backing as Mooney teaches with viscoelastic properties as disclosed in Turner and Ghosh as recited in the instant claims. The skilled person would have been motivated to do so because (i) all references are drawn to delivering stem cell-laden scaffolds to treat diseased tissues, (ii) Mooney teaches that its scaffolds are applicable to cell therapies in general, “enhance the viability of the cells and induce their outward migration to populate injured or defective bodily tissues [and] enhance the success of tissue regeneration” (para. 0004), and teaches multi-layer, porous scaffolds having only limited areas of cell egress, (iii) Turner teaches a “backing” layer for scaffold adhesion to internal organs such as kidney and the suitable viscoelasticity ranges of such applications, and (iv) Ghosh suggests that softer hydrogels (e.g., 95 Pa) may be utilized to promote cellular migration, while viscosities of 550 Pa or higher promote cellular adhesion and proliferation (Section 3.3.1,4, Fig. 5).
Regarding claims 44-46, Applicant discloses “’viscoelasticity’ refers to the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation” (para.0059, pre-grant publication US 2018/0361027), and refers to hydrogel rigidity or stiffness as “viscoelasticity (rheological) properties” (id., para.0250; see Fig. 2D, E, paras.0026, 0249-50, 0275). Therefore Turner’s shear moduli is considered a viscoelastic property, and the range of 25 to 520 Pa includes those in claims 44-46. Ghosh also teaches softer hydrogels (e.g., 95 Pa) for promoting cellular migration and gels of higher viscosities over 550 Pa for cellular adhesion and proliferation (Section 3.3.1,4, Fig. 5). One of ordinary skill in the art would have recognized the rheological properties of the scaffold material as a result-effective variable. For result-effective variables, in the case where claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP § 2144.05 (citations omitted). Furthermore a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. MPEP § 2144.05(I) (citations omitted). Optimization within prior art conditions or through routine experimentation does not support patentability absent comparative evidence of criticality of the claimed range. See MPEP § 2144.05 (II) (citations omitted).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 26-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6-20, 23, 24, and 17-33 of copending Application No. 16/006,482 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ’482 application anticipate the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 26-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of US 11129923 in view of Mooney (US 2008/0044900).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ’923 patent anticipates the patch graft of the instant claims and Mooney teaches liver tissue regeneration and repair using such patch grafts in the form of scaffolds.
Claims 26-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 33, 35-37, 46-51, 53, 54, 59, 60, and 89-94 of copending Application No. 16/422,086 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to treating or engrafting cells of a solid organ by contacting the organ with the recited patch graft. The liver is a solid organ which is recited in both claim sets.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 26-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 10, 11, 15-18, 21, 23, 28, 29, 32, 33, 39, and 40 of copending Application No. 16/006,460 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claims sets are drawn to a method of engrafting stem cells into liver, wherein the method of the ’460 application’s claims anticipate the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614