DETAILED ACTION
This action is in reply to papers filed 11/26/2025. Claims 1-20 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20190127684A1, Published 11/1/2018.
Withdrawn Objections/Rejections
The objection of claim 19 is withdrawn in view of amendments made to the claim.
The 112 (b) rejection of claim 11 is withdrawn in view of amendments made to the claim.
Applicant’s arguments regarding the 35 U.S.C §102 (a)(1) rejection of claims 13 and 15-16 as being anticipated by Singh et al. has been fully considered. The rejection of claims 13 and 15-16 is withdrawn. It is noted that the rejection has been withdrawn in view of the Declaration filed by Inventors Rizzolo and Singh. Inventors provide a Declaration establishing the relevant subject matter disclosed in Singh et al. and the disclosures of the instant application were both by the inventor or joint inventors of the present application.
Applicant’s arguments regarding the 35 U.S.C §102 (a)(1) rejection of claims 1, 2, 4-10 and 12-20 as being anticipated by Xia et al. has been fully considered. The rejection of claims 1, 2, 4-10 and 12-20 is withdrawn. It is noted that the rejection has been withdrawn in view of the Declaration filed by Inventors Rizzolo and Singh. Inventors provide a Declaration establishing the relevant subject matter disclosed in Xia et al. and the disclosures of the instant application were both by the inventor or joint inventors of the present application.
Maintained Rejections
The 103 (a) rejection of claims 1-2, 4-10 and 12-20 as being unpatentable over Ghiassi-Nejad et al. (Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1149) in view of Ediriwickrema, Lilangi S. (Yale University. ProQuest Dissertations Publishing, 2012. Abstract), Jiang et al. (Biomed Res Int. January 2017: 9474573) and Zhao et al. (Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3995) is maintained. Applicant’s arguments will be addressed following maintained rejection.
The 103 (a) rejection of claims 3 and 11 as being unpatentable over Ghiassi-Nejad et al. (Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1149) in view of Ediriwickrema, Lilangi S. (Yale University. ProQuest Dissertations Publishing, 2012. Abstract), Jiang et al. (Biomed Res Int. January 2017: 9474573) and Zhao et al. (Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3995) as applied to claims 1-2, 4-10 and 12-20 is maintained. Applicant’s arguments will be addressed following maintained rejection.
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 (i.e., changing from AIA to pre-AIA ) 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 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.
Claim(s) 1-2, 4-10 and 12-20 remain rejected under 35 U.S.C. 103 as being unpatentable over Ghiassi-Nejad et al. (Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1149) in view of Ediriwickrema, Lilangi S. (Yale University. ProQuest Dissertations Publishing, 2012. Abstract), Jiang et al. (Biomed Res Int. January 2017: 9474573) and Zhao et al. (Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3995). For Applicant’s convenience, the rejection is copied below.
Ghiassi-Nejad et al. teach retinal progenitor cells (RPC) can form neurospheres that resemble retinal structure, but their small spherical geometry limits their utility for experimentation and implantation into diseased retinas. Thus, Ghiassi-Nejad and colleagues examined different scaffolds for biocompatibility, and ability to foster stem cell growth and differentiation. Towards this end, Ghiassi-Nejad teaches scaffolds were fabricated from electrospun polycaprolactone (PCL) or from alginate or gelatin that was decorated with hyaluronic acid and chondroitin sulfate (as in claim 1 (in-part), as in claim 13 (in-part) and as in claim 18(a-in-part)). The scaffolds were freeze-dried (as in claim 4) to create large pores, rehydrated, and sectioned into discs (i.e. planar sheets) varying from 60-120 microns thick (as in claim 12). Pore size was evaluated by scanning electron microscopy, and potential toxicity was tested by implanting the scaffolds into mouse retinas (as in claim 18 (e)). Human embryonic stem cells (WA09) were differentiated into RPC (as in claim 5, as in claim 6, as in claim 13 (in-part), as in claim 16, as in claim 18(b) and as in claim 19), and in some experiments, co-cultured with human fetal (hfRPE) (as in claim 8 (in-part) as in claim 9, as in claim 13 (in-part), as in claim 15 and as in claim 20).
With respect to claim 7 and claim 17, which are drawn to wherein the retinal progenitor cells are derived from human induced pluripotent stem cells, Examiner notes that these limitations are product-by-process limitations. Product-by-process limitations are not viewed as positively limiting the product absent a showing that the process of making the product recited in the claims imparts a novel or unexpected property to the product, as it is assumed that equivalent products are obtainable by multiple routes. "Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113. In the instant case, the burden is placed upon the Applicants to establish a patentable distinction between the RPCs derived from IPS cells, as claimed, and RPCs derived from ES cells, as taught in Ghiassi-Nejad.
Continuing, Ghiassi-Nejad teach RPCs were able to differentiate on PCL and gelatin scaffolds, but growth and differentiation was impaired on alginate scaffolds. Based on this, Ghiassi-Nejad et al. teach they proceeded with gelatin-based scaffolds. Scaffolds degraded slowly in culture, but were degraded within three weeks following implantation into the subretinal space. There was no evidence of overt inflammation, retinal edema, or degeneration. When plated at low density and co-cultured with hfRPEs, RPCs (as in claim 18 (c-in-part) and claim 18 (d)) transformed from spherical cells to broad, flattened cells that extended neurite-like projections. When plated at high density, cells uniformly populated the full thickness of scaffolds as thick as 120 microns and expressed retinal markers. In concluding, Ghiassi-Nejad teach scaffolds based on freeze-dried gelatin were most successful at satisfying 3 criteria: full penetration of the scaffolds, uniform cell density in the xy-plane, and no cytotoxicity upon implantation. See Entire Abstract.
However, Ghiassi-Nejad fails to teach the scaffold further comprises laminin (as further in claim 1).
Before the effective filing date, Ediriwickrema taught that as a step towards engineering an outer retina suitable for transplantation, a biocompatible, biodegradable scaffold that allows retinal progenitor cells (RPCs) to form flat, laminar structures was developed. Continuing, Ediriwickrema teaches the scaffold minimizes the exposure of retinal progenitors to extracellular matrix components that are not found in the retina, and enables co-culture with the retinal pigment epithelium. Specifically, Ediriwickrema teaches the scaffolds were formed from electrospun fibers of polycaprolactone (PCL). RPCs derived from human embryonic stem cells (hESC-derived RPCs) were cultured to form neurospheres. Dissociated neurospheres were seeded onto +/- laminin coated PCL sheets (as further in claim 1) in normal or low O2 incubators, and maintained in two types of serum free medium. Confocal imaging confirmed that the RPCs penetrated the thickness of the scaffold irrespective of laminin coating and O2 level, and continued to express retinal markers such as Pax6, recoverin, and N-cadherin , with heightened expression in the differentiation medium. Cells adhered uniformly to laminin-coated PCL, but formed aggregates on uncoated PCL. Staining for the proliferative marker, Ki67, indicated active cell division in both medium types and O2 levels. In concluding, Ediriwickrema notes that RPC co-culture experiments with laminin coated PCL in low oxygen conditions revealed polarization of N-cadherin, with concomitant stress fiber formation in the RPE monolayer. Overall, electrospun Ediriwickrema teach PCL polymers sustained the differentiated properties acquired by neurospheres and appear to be suitable scaffolds for reconstructing an outer retinal layer. See Entire Abstract.
And although Ediriwickrema teach laminin-coated scaffold sheets, Ediriwickrema fails to teach said laminin is laminin-521 (as in claim 2, as in claim 14 and as in claim 18(a)).
Before the effective filing date of the claimed invention, Jiang et al. teach a method of producing rat bone mesenchymal stem cells (rBMSCs) sheets. Jiang teaches when rBMSCs were seeded on laminin-521 (as in claim 2, as in claim 14 and as further in claim 18(a)) coated films, these cells had a lower tendency to aggregate, since laminin-521 does not have α-1 and β-1 arms. Without local aggregation, Jiang teaches rBMSCs formed cell sheets successfully (Abstract; Pg. 10, Col. 1, para. 2).
And although Ghiassi-Nejad and Ediriwickrema taught a co-culture of retinal progenitor cells with retinal pigment epithelial cells, none of Ghiassi-Nejad et al nor Ediriwickrema teach the retinal progenitor cells are seeded on top of the retinal pigment epithelial cells (as in claim 8 and as further in claim 13).
Before the effective filing date of the claimed invention, Zhao et al. taught that in order
to restore vision, stem cell therapies for retinal degenerations must address the loss of both photoreceptors and retinal pigment epithelium. To explore the effects of each tissue layer on the other’s maturation, Zhao and colleagues co-cultured human embryonic stem cell derived retinal progenitor cells (hESC-RPC) with retinal pigment epithelium (hESC-RPE) (as in claim 10).
Specifically, Zhao teaches to generate hESC-RPC, H9 embryonic stem cells were seeded as clusters to polycaprolactone (PCL) scaffolds and cultured in retinal differentiation media. In the co-culture group, hESC-RPC cultures were placed on top of hESC-RPE monolayers during the retinal differentiation protocol (as further in claim 8 and as further in claim 13 and as further in claim 18 (c)). Transepithelial electrical resistance (TER) was monitored over time to assess RPE integrity and function. After 2-4 weeks, co-cultured tissue layers were separated and compared to controls by RT-PCR and immunofluorescence. Zhao observed the expression of neural retinal marker mRNAs by hESC-RPC in both monoculture and co-culture. Co-cultures expressed several of these markers at higher levels, including Crx and Rhodopsin. Immunofluorescence revealed multilayered clusters positive for markers including Otx2, Crx, and Recoverin. In co-cultures, these markers localized to the surface opposing the RPE. An RT-PCR array for monitoring RPE maturation showed that co-cultured hESC-RPE was more mature. In addition, co-cultured hESC-RPE maintained a high TER in retinal differentiation medium, while in controls the TER decreased after 2-4 weeks. In concluding, Zhao notes that co-culture increases the maturation of both hESC-RPC and hESC-RPE, underlining the interdependence of these tissues. Secretions of the RPE and contact with the RPE could supplement or replace media as promoters of RPC differentiation, facilitating the creation of a transplantable tissue. See Entire Abstract.
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. At the time of invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Ghiassi-Nejad, wherein Ghiassi-Nejad teach a method of producing a retina-transplantable tissue comprising seeding onto planar scaffolds comprising gelatin, chondroitin sulfate and hyaluronic acid, retinal progenitor cells and retinal pigment epithelial cells, with the teachings of Ediriwickrema, wherein Ediriwickrema teaches a co-culture of retinal progenitor cells and retinal pigment epithelial cells seeded on laminin coated surface adhered uniformly to the coated surface, with a reasonable expectation of arriving at the claimed invention. That is, one of ordinary skill in the art would have found it prima facie obvious to coat the planar scaffolds of Ghiassi-Nejad with laminin in order to keep the seeded cells from aggregating. Moreover, based on the teachings of Jiang et al., the skilled artisan would have found it prima facie obvious to coat the planar scaffolds with laminin-521 because Jiang teaches that- as a result of laminin-521 lacking α-1 and β-1 arms, cells had a lower tendency to aggregate on laminin-521. Given Ghiassi-Nejad’ s concern regarding the ability to transplant into diseased retinas spherical-shaped neurospheres, one of ordinary skill in the art would have been certainly been motivated to coat the planar scaffolds with laminin in order to keep the cells from aggregating, as taught by Jiang.
In addition, the skilled artisan would have found it prima facie obvious to seed the retinal progenitor cell culture on top of a monolayer of retinal pigment epithelial cells because Zhao noticed a faster maturation of both hESC-RPC and hESC-RPE when RPC cultures were seeded on top of RPEs. Accordingly, for the purposes of deriving a mature and transplantable tissue, the seeding arrangement would have been prima facie obvious.
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.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Applicant’s Arguments/Response to Arguments
Applicant argues: Applicant submits that a skilled artisan would have no expectation of success in arriving at the presently claimed invention based on the alleged teachings of Ghiassi-Nejad, Edirickwema, Jiang, and Zhao at least because a skilled artisan would not have any expectation of success in modifying the scaffold of Ghiassi-Nejad to include laminin to keep seeded retinal cells from aggregating. It would not have been reasonable, without the aid of hindsight bias provided by the present application, to predict that addition of laminin to the scaffold of Ghiassi-Nejad would result in retinal cells to form a monolayer rather than an aggregate.
In Response: In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that 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 the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Furthermore, one of ordinary skill in the art would have certainly had a reasonable expectation that laminin would keep the scaffold seeded retinal progenitor cells of Ghiassi-Nejad from aggregating as Edirickwema teaches retinal progenitor cells adhered uniformly to laminin-coated PCL, but formed aggregates on uncoated PCL.
Applicant’s arguments: As discussed previously, the Examiner admits that Ghiassi-Nejad fails to teach the scaffold of Ghiassi-Nejad further comprises laminin. However, the Examiner contends that Ediriwickrema teaches a co-culture of retinal progenitor cells and retinal pigment epithelial cells seeded on laminin coated surface adhered uniformly to the coated surface. However, Applicant submits that Ediriwickrema is silent to the scaffold comprising gelatin, chondroitin sulfate, and hyaluronic acid. In contrast, Ediriwickrema teaches laminin coated sheets of electrospun polycaprolactone (PCL) fibers.
In Response: Ediriwickrema et al. need not have taught a scaffold comprising gelatin, chondroitin sulfate, and hyaluronic acid, as this was taught by Ghiassi-Nejad. Note that this was an obviousness type rejection and not an anticipatory type rejection.
Applicant’s arguments: Applicant submits that a skilled artisan would understand that, without the aid of hindsight bias provided by the teachings of the present application, there would be no expectation that incorporating a laminin coating in a PCL scaffold as taught by Eridiwickrema would have the same or even similar effects on a cell culture, particularly in terms of monolayer and aggregate formation, as incorporating a laminin coating in a scaffold comprising gelatin, chondroitin sulfate, and hyaluronic acid as recited in claim 1.
In Response: In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that 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 the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Furthermore, one of ordinary skill in the art would have certainly had a reasonable expectation that laminin would keep the scaffold seeded retinal progenitor cells of Ghiassi-Nejad from aggregating as Edirickwema teaches retinal progenitor cells adhered uniformly to laminin-coated PCL, but formed aggregates on uncoated PCL.
Applicant’s arguments: Applicant submits that a skilled artisan would appreciate that the effect of the combination of coating reagents, such as laminin, underlying substrate or scaffold, cell type, and cell culturing conditions can have various and unpredictable impacts on cell culture outcomes including the propensity of cultured cells to form a monolayer or aggregate. Applicant submits that a skilled artisan would understand the unpredictability of cell culture and particularly monolayer and aggregate formation
In Response: Applicant’s arguments regarding unpredictability are not found persuasive. Per MPEP 716.01(c), the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602.
Applicant’s arguments: For example, Liberia et al. (2014, PLoS One 9:el 12122; provided herein as "Exhibit A"; hereinafter "Liberia") discusses different coating reagents, including laminin, and culturing conditions and their impact on cell proliferation, cell adhesion, morphology, and other aspects of a cell culture. Specifically, Liberia teaches that laminin as a coating reagent increased mobility, generally did not improve adherence, and promoted cell aggregation in androgen-sensitive human prostate adenocarcinoma cell line (LNCaP) cultures compared to other coating reagents or non-coated controls (Liberia, Abstract and Table 1 ). This result in terms of cell aggregation effects is in direct contrast to the effects of using laminin as a coating reagent in the context of Ediriwickrema which decreased cell aggregation. The context of Ediriwickrema differs at least in cell type and underlying substrate to Liberia. Therefore, a skilled artisan would understand that the incorporation of laminin as a coating reagent in cell cultures is dependent on context and difficult to predict without conducting appropriate experiments.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Note that Liberio et al. teaches weak cell-surface adhesion of cell lines is a common problem of tissue culture research and presents technical limitations to the design of experiments. Their characteristically weak attachment to the surface of tissue culture vessels and cover slips have impeded their manipulation, analysis and use in high throughput screening since LNCaP cells can be easily dislodged through modest mechanical forces like fluid shear stress (Pg. 2, Col. 1). And in ‘Conclusion’ Liberio adds LNCaP cells are the most popular model to study AR-regulated pathways in prostate cancer; however, their use is technically challenging due to their weak cell-substrate adherence. Thus, a comparison between LNCaP cells, which Applicant’s own cited art teaches has “weak” adherence cannot be compared to cells (retinal) that are known in the art to be inherently adherent.
Applicant’s arguments: Applicant also submits that Jiang does not provide a reasonable expectation of success in predicting that the addition of laminin, particularly laminin-521, to the scaffold of Ghiassi-Nejad would result in cells forming a monolayer rather than an aggregate. As discussed previously, the Examiner contends that based on the teachings of Jiang, the skilled artisan would have found it prima facie obvious to coat the planar scaffolds with laminin-521 because Jiang teaches that as a result of laminin-521 lacking α-1 and β-1 arms, cells had a lower tendency to aggregate on laminin-521. Applicant submits that a skilled artisan would understand that laminins are a large family of heterotrimeric basement membrane adhesion proteins that are highly cell and tissue type specific. Applicant submits that a skilled artisan would understand that the teachings of Jiang, which pertain to rat bone marrow mesenchymal stem cells, would not provide a reasonable expectation of success of culturing retinal tissue, as recited in independent claims 1 and 18, or of differentiating retinal pigment epithelial and retinal progenitor cells as recited in independent claim 13. Applicant submits that a skilled artisan would appreciate the unpredictability in the art of cell culture and would appreciate that the effects of using any cell culture reagents in different contexts may produce unpredictable outcomes.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. As noted by Applicant, laminins are a large family of heterotrimeric basement membrane adhesion proteins, thus there is a reasonable expectation that retinal cells- taught to be adherent on the generically laminin-coated surface in Ediriwickrema would also be adherent on the laminin-521 surface of Jiang. Nevertheless, and solely to rebut Applicant’s argument, Examiner cites Koizumi et al. (PgPub US20170319665A1, Filed 10/30/2015) who teach laminin 411, laminin 511, laminin 521, and laminin 511-E8 fragments significantly promoted cell adhesion of the retinal pigment epithelium. Koizumi also teaches that significant promotion of cell adhesion of a retinal pigment epithelium was not observed for laminin 111, laminin 211, and laminin 332 (Pg. 18, para. 278). Note that all laminins tested had some modicum of RPE cell adhesion.
Applicant’s arguments: For example, Rodin et al. (2014, Nature communications 5:3195, 1-13; provided herein as "Exhibit B"; hereinafter "Rodin") discusses a method for the derivation and self-renewal of human embryonic stem (hES) cell lines by developing a cell culture matrix containing laminin- 521. Rodin teaches that the addition of laminin-521 alone to the cell culture does not enable clonal survival of hES cells and that the cells appear to require migration and cell-cell contact for the proliferation (Rodin, Abstract and Figure 4). This result of Rodin is in direct contrast to the results of laminin-521 addition to a cell culture in the context of Jiang which teaches that laminin-521 could promote the formation of rat bone marrow mesenchymal stem cell sheet with good viability. The cell cultures of Rodin and Jiang differ at least in cell type. Therefore, a skilled artisan would understand that the outcome of incorporating laminin-521 into a cell culture is dependent on context, and difficult to predict without conducting appropriate experiments to determine the outcome empirically.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Applicant’s arguments are off point as Fig. 4 is clearly drawn to inhibiting hES cell adhesion by E-cadherin. See below. No such experiment was performed in Jiang.
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Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Claims 3 and 11 remain rejected under 35 U.S.C. 103 as being unpatentable over Ghiassi-Nejad et al. (Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1149) in view of Ediriwickrema, Lilangi S. (Yale University. ProQuest Dissertations Publishing, 2012. Abstract), Jiang et al. (Biomed Res Int. January 2017: 9474573) and Zhao et al. (Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3995) as applied to claims 1-2, 4-10 and 12-20 above, and further in view of Kuo et al. (J Biomed Mater Res A. 2008 Sep 15;86(4):1062-8.).
The teachings of Ghiassi-Nejad et al., Ediriwickrema, L., Jiang et al., and Zhao et al. are relied upon as detailed above. However, none of the aforementioned references teach the three-dimensional monolith is formed by crosslinking (as in claim 3) and that the monolith comprises a ratio of concentrations of gelatin, chondroitin sulfate, and hyaluronic acid, wherein the ratio is 2:1:2 (as in claim 11).
Before the effective filing date of the claimed invention, Kuo et al. taught a gelatin-chondroitin sulfate-hylauronan tri-copolymer scaffold for the purposes of regenerating dental-pulp tissue in vivo. Kuo teaches gelatin powder (0.5 g), sodium hyaluronate (HA) (5 mg, 0.5 mL), and chondroitin-6-sulfate (C6S) powder (0.1 g) were mixed with double-distilled water and crosslinked for 2–3 min at 25°C using 2 mL of 1% 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC) (as in claim 3) (Pg. 1063, Col. 1, para. 2). Kuo teaches the scaffold has good biocompatibility, biodegradable, and produces nontoxic metabolites. In addition, Kuo teaches previous studies had shown that this scaffold had provided information for cell attachment (Pg. 1063, Col. 1, para. 1).
With respect to claim 11, per MPEP 2144.05, "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Additionally, the Courts have consistently held that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). Thus, experimentation to determine the optimum concentration of gelatin-chondroitin sulfate-hylauronan tri-copolymer scaffold for the purposes of retinal tissue engineering was well known in the art of tissue engineering. As such, obtaining the resulting composition to function as claimed would require only routine experimentation for one of ordinary skill in the art.
Therefore, given that the combination of the claimed components has been previously described, without specific evidence that the indicated concentrations are critical to the invention; the identification of these properties will not render the subject matter patentable.
Accordingly, the claims are obvious in view of Ghiassi-Nejad et al., Ediriwickrema, L., Jiang et al., Zhao et al., and Kuo et al.
Applicant’s Arguments/Response to Arguments
Applicant argues: Applicant submits that, as discussed above, none of Ghiassi-Nejad, Ediriwickrema, Jiang, and Zhao, alone or in any combination, provide a reasonable expectation of success of arriving at the subject matter of claim 1, upon which claims 2-12 depend. Applicant also submits that Kuo does not provide a reasonable expectation of success of incorporating laminin into a scaffold comprising gelatin, chondroitin sulfate, and hyaluronic acid as recited in claim 1.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Arguments drawn to the rejection of claim 1 has been previously addressed, and will not be addressed herein. Moreover, a reasonable expectation of success in including the teachings of Kuo et al. is present as Kuo specifically teaches the scaffold has been previously used in cell attachment studies.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632