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 .
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-10, as amended, originally presented, or previously presented, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, of U.S. Patent No. 11,591,564. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims discloses a species of the instant claims.
Regarding instant claim 1, patent claim 7 discloses at least one pluripotent stem cell that is deposited into a composition comprising biocompatible hydrogel linked to polypeptides comprising cell-binding sequence of an epithelial cadherin extracellular domain.
Also patent claim 1 states a composition comprising biocompatible hydrogel linked to polypeptides comprising cell-binding sequence of an epithelial cadherin extracellular domain for use with human pluripotent stem cells. It does not expressly state that the pluripotent stem cell is encapsulated by the hydrogel. However, it would be obvious to use the hydrogel as substrate with the cells including growing on it in vitro or into it in vitro (i.e. encapsulate).
Regarding instant claim 2, patent claims 1 and 7 disclose that the hydrogel is natural or synthetic polysaccharide hydrogel.
Regarding claim 3, patent claim 2 discloses a carboxylated polysaccharide hydrogel as claimed.
Regarding claim 4, patent claim 3 specifies the hydrogel as alginate.
Regarding claim 5, patent claim 1, 3, and 10 specify human pluripotent stem cell. Patent claim 8 specifies an embryonic stem cell. Patent claim 9 specifies an induced pluripotent stem cell.
Regarding claims 6-7, patent claim 1 discloses the sequences of SEQ ID NOS:2-5. Patent claim 4 discloses sequences having at least five consecutive aa of SHAVSS or ADTPPV. Both disclose a sequence comprising the AA sequence HAV or ADT.
Regarding claim 8, patent claim 1 teaches direct linkage by an amide bond.
Regarding claim 9, patent claim 5 discloses the pendent free limitations of claim 9.
Regarding claim 10, patent claim 6 discloses the composition is anionic and is in the form of capsules formed with a divalent cation.
In the remarks, Applicant submit a terminal disclaimer, if appropriate, upon withdrawal of the statutory rejections. In response, the rejection is maintained.
Claim Rejections - 35 USC § 103
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.
(1) Claims 1-5, 9 and 10, as amended, originally presented, or previously presented, is/are rejected under 35 U.S.C. 103 as being obvious over Banerjee (Disclosure for grant on 6/16/15; abstract; pp 1-2; of record in IDS) in view of Darrabie (Darrabie et al. Journal of Microencapsulation, September 2006; 23(6): 613–621).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Regarding claim 1, Banerjee teaches that in this work, the investigators propose to overcome these shortcomings through the design of novel biomimetic hydrogel capsules for scalable culture of hPSCs. Specifically, they propose to incorporate synthetic bioactive peptides mimicking cadherin and non-cadherin cell-cell interactions within three dimensional (3D) microporous hydrogel capsules, for encapsulating and propagating hPSCs (i.e.- a composition for use in propagating pluripotent stem cells). These peptide-conjugated hydrogel capsules (i.e. - a biocompatible hydrogel, optionally synthetic or naturally derived) will be designed to mimic the cellular microenvironment by synthetically recreating cell-cell contacts through epithelial-cadherin (E-cadherin) (i.e. - linked to a polypeptide comprising a cell-binding sequence of an epithelial cadherin, optionally human epithelial cadherin, extracellular matrix). Alternate peptide designs and combinations will be screened in an alginate array platform to select for those supporting short-term viability and proliferation. Further, macroporous capsules will be synthesized from the designed peptide-conjugated alginate to facilitate homogeneity in hPSC aggregates. The capsule design will also prevent coalescence of the aggregates. hPSCs propagated in alternate capsule designs will be characterized for long-term viability, pluripotency and scalability. Recreating cell-cell contact is expected to significantly enhance single cell viability and clonal expansion over current state-of-art of inhibiting Rho associated coiled coil protein kinase (ROCK) pathway. Furthermore, hydrogel encapsulation will protect the cells from bioreactor hydrodynamic stresses, hence removing shear-induced variations in the culture (p. 2, last paragraph of abstract).
Banerjee is silent as to whether the alginate hydrogel is crosslinked. However, almost a decade before the effective filing date of the instant application, Darrabie teaches microencapsulation and immunoisolation of cells for transplantation in alginate microcapsules. Although soluble in monovalent cationic solutions, alginate, when introduced to certain divalent cations, such as Ba++ and Ca++, forms cross-linkages between its polymer chains. The microencapsulation procedure entraps tissue in a semi-permeable gel sphere. Applying a cationic polyaminoacid layer such as poly-L-lysine selectively allows insulin, glucose and other nutrients to traverse the microcapsule membrane, while preventing immune system components such as immunoglobulins from destroying the encapsulated tissue. Once the perme-selective coating is performed, the inner alginate gel core can in some cases be liquefied by chelation of the gelling cation, such as Ca++. (p. 613-614).
As such, it would have been obvious to an artisan of ordinary skill before the effective filing date to use known an alginate hydrogel crosslinked with divalent, Ca++ or Ba++ taught by Darrabie in forming the alginate microcapsule encapsulating pluripotent stem cells taught by Banerjee to predicably arrive at the limitations of claim 1. The artisan would have a reasonable expectation of successfully making such a variant because Darrabie teaches that long before the time effectively filing microcapsules for encapsulating cells that are made of crosslinked alginate were successfully being made and used in the prior art. Further, Darrabie teaches that that this crosslinked alginate allowed for immunoisolation along with nutrient passage into the microcapsule without immune system components destroying the encapsulated cells. As such, Banerjee in view of Darrabie render claim 1 obvious.
Regarding claims 2-4, both Banerjee and Darrabie teach alginate, meeting the limitations of claims 2-4. As such, Banerjee in view of Darrabie teaches renders claims 2-4 obvious.
Regarding claim 5, Banerjee discloses pluripotent stem cells as claimed. Thus Banerjee in view of Darrabie render claim 5 obvious.
Regarding claim 9, Banerjee does not disclose the claimed ranges of free carboxylate groups, wherein 99% of less….1% or less of monomers of the hydrogel. However, the ranges claimed essentially encompass all possible carboxylate groups except 100%. As such, it would have been obvious to an artisan of ordinary skill that Banerjee would have to fall somewhere within this range because the disclosed ranges cover all possibilities of free carboxylate groups. Thus Banerjee in view of Darrabie renders claim 9 obvious.
Regarding claim 10, Banerjee in view of Darrabie teaches the composition is anionic and is in the form of capsules formed with a divalent cation as discussed above.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. The claimed method was known in the art at the time of filing as indicated by Banerjee in view of Darrabie. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
(2) Claims 6-8, a previously or originally presented, is/are rejected under 35 U.S.C. 103 as being obvious over Banerjee (Disclosure for grant on 6/16/15; abstract; pp 1-2; of record in IDS) in view of Darrabie (Darrabie et al. Journal of Microencapsulation, September 2006; 23(6): 613–621), as applied to claims 1-5, 9 and 10, in further view of Brinchman (WO 2008/157324), Sinaga (Sinaga et al. Pharm Res 19(8):1170-1179, 2002: of record in IDS) and Li (Li et al. Cell Adhesion and Migration 60:59-79, 2012; of record in IDS). .
Regarding claims 6-8, Banerjee in view of Darrabie teaches the composition comprising pluripotent stem cells encapsulated by a crosslinked alginate hydrogel comprising a linked polypeptide comprising a cell-binding sequence of E-cadherin extracellular domain as discussed above. Banerjee in view of Darrabie does not the claimed species of the E-cadherin polypeptide in claims 6-7. Banerjee also does not tach the polypeptide is linked by an amide bond (claim 8).
However, Brinchman teaches biostructures comprising modified alginates entrapping one or more stem cells. The modified alginates comprise at least one alginate chain section to which is bonded by covalent bonding (amide bond) at least one cell attachment peptide (p. 2, lines 22-25). Further, Brinchman teaches that these attachment polypeptide allows for development of polymers onto which these adhesive peptides can be conjugated to facilitated stem cell adhesion (p. 1, line 12-30).
Sinaga teaches peptide derived from the bulge (HAV-peptides) and groove (ADT-peptides) regions of the extracellular 1 (EC-1) domain of human E-cadherin (abstract). Sinaga more specifically discloses HAV-10 (SEQ ID NO:2); Hav-6 (SEQ ID NO:3); ADT10 (SEQ ID NO:4); and ADT6 (SEQ ID NO:5). See page 1172, Table I). Sinaga further teaches that both the groove and bulge regions of the EC-domain are important for cadherin-cadherin interactions (abstract).
Further, Li teaches that E-cadherin mediate cell-cell cohesion plays an important role in the survival and self-renewal of hESC (p. 61 sentence bridging paragraph 1 and 2).
As such, it would have been obvious to the artisan of ordinary skill at the time of effective filing to covalently link via an amide bone the species of HAV and/or ADT e-cadherin cell-binding sequences, as taught by Sinaga, to the alginate hydrogel capsule, taught by Banerjee in view of Darrabie, using the means taught by Brinchman, to predictably arrive at the alginate hydrogel linked to a polypeptide comprising a cell-binding sequence of an human e-cadherin EC domain as claimed. An artisan would have a reasonable expectation of success because both Brinchman provides a successful means of covalently linked cell-binding sequences to alginate polymers for stem cell culture and the e-cadherin cell-binding sequences were known in the art, as taught by Sinaga. Further, an artisan would be motivated to include these human e-cadherin cell binding sequences, taught by Sinaga, to the alginate polymer capsule of Banerjee in view of Darrabie because Brinchman teaches that the cell adhesion polymers provide improved environment for the stem cells, and Li more particularly teaches that E-cadherin mediate cell-cell cohesion which plays an important role in the survival and self-renewal of hESC. Thus, Banerjee in view of Darrabie in further view of Brinchman, Sinaga, and Li render the claims obvious.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. The claimed method was known in the art at the time of filing as indicated by Banerjee in view of Darrabie in further view of Brinchman, Sinaga, and Li. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
(3) Claim(s) 1-20, as amended, previously presented, or originally presented, is/are rejected under 35 U.S.C. 103 as being unpatentable over Maguire (US 2009/0311765 Pub date:12/17/2009; of record in IDS) in further view of Brinchman (WO 2008/157324), Sinaga (Sinaga et al. Pharm Res 19(8):1170-1179, 2002: of record in IDS) and Li (Li et al. Cell Adhesion and Migration 60:59-79, 2012; of record in IDS).
Regarding claim 1, Maguire teaches a single cell suspension of embryonic stem cells encapsulated within an alginate polyelectrolyte microenvironment (p, 10; claim 1). These teachings encompass the limitations a composition comprising at least one pluripotent stem cell encapsulated within a 3D biocompatible hydrogel.
Maguire does not teach that the hydrogel is linked to a polypeptide comprising a cell-binding sequence of an epithelial cadherin extracellular domain.
Brinchman teaches biostructures comprising modified alginates entrapping one or more stem cells. The modified alginates comprise at least one alginate chain section to which is bonded by covalent bonding (amide bond) at least one cell attachment peptide (p. 2, lines 22-25). Further, Brinchman teaches that these attachment polypeptide allows for development of polymers onto which these adhesive peptides can be conjugated to facilitated stem cell adhesion (p. 1, line 12-30).
Sinaga teaches peptide derived from the bulge (HAV-peptides) and groove (ADT-peptides) regions of the extracellular 1 (EC-1) domain of human E-cadherin (abstract). Sinaga more specifically discloses HAV-10 (SEQ ID NO:2); Hav-6 (SEQ ID NO:3); ADT10 (SEQ ID NO:4); and ADT6 (SEQ ID NO:5). See page 1172, Table I). Sinaga further teaches that both the groove and bulge regions of the EC-domain are important for cadherin-cadherin interactions (abstract).
Further, Li teaches that E-cadherin mediate cell-cell cohesion plays an important role in the survival and self-renewal of hESC (p. 61 sentence bridging paragraph 1 and 2).
As such, it would have been obvious to the artisan of ordinary skill at the time of effective filing to covalently link via an amide bone the species of HAV and/or ADT e-cadherin cell-binding sequences, as taught by Sinaga, to the alginate hydrogel capsule, taught by Maguire, using the means taught by Brinchman, to predictably arrive at the alginate hydrogel linked to a polypeptide comprising a cell-binding sequence of an human e-cadherin EC domain as claimed. An artisan would have a reasonable expectation of success because both Brinchman provides a successful means of covalently linked cell-binding sequences to alginate polymers for stem cell culture and the e-cadherin cell-binding sequences were known in the art, as taught by Sinaga. Further, an artisan would be motivated to include these human e-cadherin cell binding sequences, taught by Sinaga, to the alginate polymer capsule of Maguire because Brinchman teaches that the cell adhesion polymers provide improved environment for the stem cells, and Li more particularly teaches that E-cadherin mediate cell-cell cohesion which plays an important role in the survival and self-renewal of hESC. Thus, Maguire view of Brinchman, Sinaga, and Li render the claims obvious.
Regarding claims 2-4, Maguire teaches an alginate capsule as discussed above.
Regarding claim 5, Maguire teaches an embryonic stem cell as discussed above.
Regarding claims 6-8, Maguire does not teach the specific species of E-cadherin polypeptides (claims 6-7) linked to the hydrogel by an amide bond. However, Brinchman, Sinaga, and Li teach these missing limitations in Maguire and provide reasonable expectation of success and motivation to combine these prior art elements as discussed above.
Regarding claim 9, neither Maguire nor the secondary references expressly teach the claimed ranges of free carboxylate groups, wherein 99% of less….1% or less of monomers of the hydrogel. However, the ranges claimed essentially encompass all possible carboxylate groups except 100%. However, it would have been obvious to an artisan of ordinary skill that both Maguire the secondary references would have to fall somewhere within this range because the recited ranges cover all possibilities of free carboxylate groups. Thus Maguire in view of Brinchman, Sinaga, and Li renders claim 9 obvious.
Regarding claim 10, Maguire teaches a single cell suspense of embryonic stem cells encapsulated with an alginate polyelectrolyte microenvironment ([0031]). The alginate polyelectrolyte microenvironment includes a divalent cation. Suitable divalent cations include Ca2+ or Ba2+ ([0032]). Alginate is anionic. As such, Maguire teaches the composition is anionic and is in the form of capsules formed with a divalent cation as claimed. As such, Maguire in view of Brinchman, Sinaga, and Li renders claim 10 obvious.
Regarding claim 11, Maguire teaches methods for producing encapsulated embryonic stem cells. In one embodiment, the method includes providing a single cell suspension of ES cells; and combining this single cell suspension of ES cells with an alginate solution to form a mixture. This method further includes subjecting the mixture to an electrostatic field to form electrostatic alginate droplets; and exposing the electrostatic alginate droplets to a divalent cation solution to form a bead about the ES cells ([0080]). As such Maguire in view of Brinchman, Sinaga, and Li render claim 11 obvious for reasons discussed above.
Regarding claim 12, Maguire teaches the divalent cation is Ca2+ or Ba2+ as discussed above. In the examples Ca2+ is used in the form of CaCl ([0087]). Therefore, Maguire in view of Brinchman, Sinaga, and Li renders claim 12 obvious.
Regarding claim 13, Maguire teaches embryonic stem cells not “induced pluripotent stem cells”. However, the claims do not recite any addition structural or functional limitations that would distinguish the induced pluripotent stem cell from the embryonic stem cell. As such, stating it is “induced” solely recites the means by which the pluripotent stem cell is made and does not necessarily impart additional structural or functional limitation to the claimed pluripotent stem cell. As such, the breadth of the claimed induced pluripotent cell encompasses any pluripotent cells such as the embryonic stem cell of Maguire. As such, Maguire in view of Brinchman, Sinaga, and Li teach the requisite limitations of the claim and render it obvious for reasons discussed above.
Regarding claim 14, Maguire teaches that the embryonic stem cells can be of human origin ([0033]).
Regarding claim 15, Maguire does not teach the specific species of E-cadherin polypeptides linked to the hydrogel by an amide bond. However, Brinchman, Sinaga, and Li teach these missing limitations in Maguire and provide reasonable expectation of success and motivation to combine these prior art elements as discussed above.
Regarding claims 16-18, Maguire teaches an alginate hydrogel as discussed above, which meets the limitations of a polysaccharide monomer (claim 16), a synthetic or natural monomer (claim 17), and alginate (claim 18).
Regarding claims 19-20, Maguire does not teach the specific species of E-cadherin polypeptides linked to the hydrogel by an amide bond. However, Brinchman, Sinaga, and Li teach these missing limitations in Maguire and provide reasonable expectation of success and motivation to combine these prior art elements as discussed above.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. The claimed method was known in the art at the time of filing as indicated by Maguire in view of Brinchman, Sinaga, and Li. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Response to Arguments
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive.
Applicant submits that the claims have been amended to specify the pluripotent stem cells as human pluripotent stem cells and also amended the claims to clarify the effect of the interaction between those cell(s) and the cross-linked hydrogel. Applicant has also submitted a declaration by Dr. Banerjee that was filed in the parent application describes the unique nature of human pluripotent stem cells (hPSCs). hPSCs are a subset of stem cells that are susceptible to dissociation-induced apoptosis. This means that hPSCs require cell-cell contact to survive and loss of contact triggers the apoptotic pathway. Thus while other stem cells types can be cultured in as single cells, special care is needed to enable single cell culture and propagation of hPSCs. Thus any substrate and culture techniques that are considered suitable for stem cells propagation may not be adequate for hPSCs propagation. To this end, Darrabie is insufficient for viability and propagation of hPSC. Darrabie contains no teaches or suggestion that cross-linked, alginate hydrogel may be suitable for encapsulation that allows hPSCs to remain viable and to propagate. Darrabie does not provide guidance to any data as to cell viability and applicability to hPSC unique needs.
In response, Applicant is not considering the generic nature of the claims, the teachings of the primary reference, and that Darrabie not provided to teach culture requires of hPSC. The claim, in fact, is not to a culture but a composition so unique culturing requirements are not required to meet the limitations of the claimed composition. Examiner acknowledges the wherein clause added by amendment describes an interaction between the hPSC and the hydrogel and that this interaction allows for viability and propagation of the hPSC. However, wherein clause does not actually further structurally or functionally limit the claimed composition but rather recites a type of conditional limitations of capacity of the claimed composition when placed in conditions for cell propagation. As such, the declaration’s discussion of the particular culture needs of hPSC in not persuasive because the claim does not require culture and is not a method. All the claim requires is a composition with the structural elements of hPSC encapsulated in the claimed hydrogel linked to an e-cadherin polypeptide. Further, the primary reference Banerjee teaches incorporating e-cadherin peptides in to an alginate hydrogel for the express purpose for propagating hPSC. As such, Darrabie is not required to teach these limitations because they are already address by Banerjee. Darrabie is solely provided because Banerjee is silent as to crosslinking the alginate hydrogel used for encapsulation. Banerjee already teaches that the e-cadherin is the structural element that support hPSC propagation in the hydrogel encapsulation system and there is no apparent reason to believe that crosslinking in a manner taught by Darrabie should counter that ability of the alginate hydrogel comprising e-cadherin polypeptide to promote hPSC propagation. As such, given the all the elements of the composition are structurally taught by Banerjee and the specifics of crosslinking such an alginate encapsulation system for use with cells is also known in the prior art including motivation to use such crosslinking as taught by Darrabie, the claims continue to be renders obvious by Banerjee in view of Darrabie.
Applicant submits that in addition to Darrabie, Brinchmann, which is distinguishable based on its use of RGD peptides, which is shown in the a second declaration, is insufficient for viability and propagation of hPSC. Sinaga does not address viability and propagation of hPSC as well.
In response, these references were not provided to teach viability and propagation conditions. Further for reason already discussed above, these are not required of the claimed composition but rather are describing a conditional capacity of the composition when claimed in culture conditions or condition for propagation. As such, these arguments are not persuasive.
Applicant submits Maguire is limited to an alginate polyeletrolyte microenvironment and is silent to peptides linked to the hydrogel. Brinchmann is of no value to the skilled artisan because as discussed in the second declaration discussing Brinchmann, Dr. Banerjee showed experimental evidence that the use of RGD does not grow and propagate hPSC. Sinaga merely discloses e-cadherin can increase porosity in kidney cell monolayers which has no relevance to the claimed subject matter. As such, these combined teaching do not render the claims obvious.
In response, Applicant is overlooking the actual cited teachings from these references and only points to other elements present in the reference not relied upon for the teachings and rationale in the actual rejection. Maguire teaches PSC encapsulated by alginate hydrogel. As acknowledged Maguire does not teach the polypeptides linked to the hydrogel. Brinchman was not provided for its teaching specifically of RGD but to demonstrate that method of introducing such polypeptides into alginate hydrogel that can be used for encapsulation was established in the prior art. Singaga provide such polypeptides, particularly e-cadherin of the claimed SEQ ID NO and Li provide motivation for adding e-cadherin polypeptides. Brinchmann’s specific teaching of RGD and Sigaga’s teaching regarding porosity in another cell type are not relevant to the rejection was made because these are not used for these teachings in the rejection of record. As such Applicant’s arguments are not found persuasive.
In conclusion, the claims as amended are still taught by the cited combined art and Applicant’s argument as not sufficient to overcome the rejections of record. Applicant is not considering the generic nature of the claimed invention and is not considering the full teachings of the cited prior art that provide ample showing of obviousness.
Declarations
The declaration of Dr. Banerjee (referred to as first declaration herein) under 37 CFR 1.132 filed 11/11/2025 is insufficient to overcome the rejection of claims 1-20 based upon 35 USC 103 as set forth in the last Office action because: The first declaration does not demonstrate that Brinchmann as used in the rejection of record will not effectively lead to the claimed invention. This declaration was used the parent application to address a different rejection but some of the same prior art used in the pending 103 rejections in the instant application. The declaration discusses Brinchmann’s uses for introducing RGD polypeptides into alginate for entrapping stem cells. The declaration points out that that Brinchman does not use e-cadherin polypeptides and is silent as to culture and propagation of hPSC and this omission is critical because hPSC are a subset of stem cells that are susceptible to dissociation-induced apoptosis in a manner that other stem cell types are not. The first declaration further provide experimental evidence that RGD will not support hPSC survival and growth.
As discussed in greater detail above, the first declaration is not sufficient to demonstrate Brinchmann would not have a reasonable expectation of success because the claims are not to a culture but a composition that does not require cell propagation. Further, Brinchmann was not provided in the rejection to teach RGD but rather to provide a methodology of introducing short polypeptides int crosslinked alginate hydrogel encapsulation systems. The first declaration does not address these specific teachings of Brinchmann and the ability of the method used to link small peptides to the alginate gel as used in the rejection. As such, these particular teachings regardless of RGD would be considered predictable and provide successful means of introducing such polypeptide into alginate hydrogels. As such, the first declaration is not sufficient to overcome the obviousness rejections of record.
The second declaration under 37 CFR 1.132 filed 11/11/2025 is insufficient to overcome the rejection of claims 1-20 based upon 35 USC 103 as set forth in the last Office action because: Similar to the first declaration, the second declaration provide a discussion and provides a additional art to show that hPSC are not like other the stem cell types and have unique requirements for culture, survival and propagation. As such, the second declaration suggest that their design using alginate linked to e-cadherin is an unexpected results.
In response, the second declaration is not sufficient to demonstrate non-obviousness and unexpected results because it not considering the generic nature of the claimed product and that survival and propagation, while being a conditional capability when place under culture and propagation conditions, is not a structural and function requirement as written. See above discussion of Applicant’s arguments for more detail.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632