CTFR 17/914,134 CTFR 86481 DETAILED ACTION Claims 1-2, 4-7, 9, 11, 15-26 are currently pending. Claims 7, 9, 11, 15-19 and 21-26 are currently under examination. Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Withdrawn Rejections The prior rejection of claim 9 under 112(d) is withdrawn as a result of Applicant amended instant claim 9 to further define placement to be topically. The prior rejection of claims 21-22 under 112(b) is withdrawn as a result of Applicant’s claim amendments to clarify the reduction in FAK and use of a conjunction. Examiner’s Note Applicant's amendments and arguments filed 04/27/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 04/27/2026, it is noted that claim 7, 19 and 21-22 has been amended. No new matter or claims have been added. New Rejections : The following rejections are newly added based on Applicant’s claim amendments. Claim Rejections - 35 USC § 112- New Matter 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 07-31-01 Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 19 contains the newly added limitation “30-100 micrograms per gram wounded tissue by weight”. Support can be found in the instant specification 30 to about 100 micrograms/g tissue by weight of the FAK inhibitor [0015]. No support can be found in the instant specification for wounded tissue by weight. Alternatively, if Applicant believes that support for claim 19, drawn to 30-100 micrograms per gram wounded tissue by weight, is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must, in responding to this Office Action, point out with particularity, where such support may be found. Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence. Claim Rejections - 35 USC § 112 (b) 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 7, 9, 11, 15-19 and 21-26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 7 contains the limitation “such as hair follicle and cutaneous glands”. Regarding claim 1, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 9, 11, 15-19 and 21-26 are further rejected as not clearing the ambiguity of claim 7. Claim 19 is directed to wherein the effective amount of the focal adhesion kinase inhibitor is from 30 to 100 micrograms per gram of wounded tissue by weight. It is unclear where tissue starts and wounded tissue ends, thus leading to unclear concentration. Modified Rejection : The following rejection is modified based on Applicant’s claim amendments. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim (s) 7, 9, 11, 15-18 and 21-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ma (Applicant provided) in view of US 2017/0157296 (previously applied) . Regarding claims 7, 9 and 16, the limitation of a method of promoting tissue healing while reducing fibrosis in a large mammal, comprising disposing a composition comprising an effective amount of a focal adhesion kinase inhibitor disposed in pores of a pullan-collagen hydrogel scaffold in proximity to a tissue wherein the tissue comprises a wound, releasing the Fak inhibitor from the compristion into the proximity of the wounded tissue and reducing a level of focal adhesion kinase for a selected period of time, thereby reducing fibrosis while inducing regenerative cell populations to promote skin regeneration including regeneration of secondary structures such as hair follicles and cutaneous glands and healing the wounded tissue is met by Ma teaching FAK inhibitor can be attenuate scar development. The use of Pullulan collagen-based hydrogel to delivery FAKI to excisional and burn wounds in mice. Drug-laden hydrogel was developed for rapid and sustained release of FAKI for treatment of burn wounds and excisional wounds. FAKI via pullulan collagen hydrogel accelerated wound healing and reduced collagen disposition and activation of scar-forming myofibroblasts in both wound healing models (abstract). FAKI is taught to be incorporated into the porous hydrogel, which enabled slow and sustained release of the FAKI to the wound environment over a few days (page 2453, first column, first paragraph). Reduced inflammation and fibrosis in an incision HTS model using FAK knockout mice is taught (page 2452, second column, second paragraph, page 2456, second column, last paragraph). Thus Ma teaches that the active step of disposing the claimed composition and releasing the FAKI and thus would necessarily result in reducing fibrosis while inducing regenerative cell population to promote skin regeneration, including regeneration of secondary structures and healing the wounded tissue. The limitation of wherein the FAK inhibitor is the elected VS-6062 is met by Ma teaching VS-6062. Ma teaches the wound is taught to use silicone rings to prevent wound contracture (primary means of rodent wound healing) but to allow the wound to closely re-epithelization (similar to human wounds (page 2458, second column, last paragraph, page 2452, second column, last paragraph, page 2453, second column, second paragraph). Thus Ma teaches the desire to treat humans and mimicking human wound healing. Regarding claim 11, the limitation of wherein the pullan collagen hydrogel is a thin film is met by Ma teaching hydrogel films were 2 mm thick (page 2457, second column, second paragraph). 2mm meets the definition of thin film, absent a definition of thin, as thin is a relative term. Regarding claim 15, the limitation of wherein the wound is a burn is met by Ma teaching the treated tissue is a burn (abstract). Regarding claims 17-18, the limitation of wherein the selected period of time for treatment with the composition comprising the FAK inhibitor is from about 7 days to about 100 days is met by Ma teaching administration for 17 days (Figure 3, page 2453) wherein the dressing is replaced every day 2-3 days and then every other day thereafter (page 2459, first column, second paragraph). Regarding claims 21-26, claims 21-26 are directed to FAK inhibit modulations mechanical signaling and promotes tissue regeneration, induces reduction of transcription or translation of three or more genes, induces regenerative cell population, induces a disruption in mechanotransduction in the large mammal and induces increased MMP1 and MMP3 expression in the large mammal. Ma teaches that the active step of disposing the claimed composition and releasing the FAKI and thus would necessarily result in functions of the FAK inhibitor, as claimed. Ma does not specifically teach a large mammal having an adult weight of greater than about 7 kilograms (claim 7). The ‘296 publication teaches compositions for enhanced healing of wounds, e.g. cutaneous wounds by application of a scaffold comprising a hydrogel film (abstract). The hydrogel is taught to be pullulan and collagen ([0011]-[0012]). The composition is taught to include porous wound dressings and the like used to treat dermal tissues including burn wounds [0075]. Treatment is taught to be applied to wound of a subject wherein the subject includes mice, pigs, rate and primates including humans [0081]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to apply the composition of Ma to human as the ‘296 publication teaches mammals to be treated include mice and humans. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as Ma and the ‘296 publication are both directed to composition including pullulan-collagen scaffolds used to treat burns, thus it would be obvious to use the compositions of Ma to treat the patient population disclosed by the ‘296 publication and Ma teaches the desire to treat humans an mimics human wound healing . 07-22-aia AIA Claim (s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ma and US 2017/0157296 as applied to claim s 7, 9, 11, 15-18 and 21-26 above, and further in view of US 2005/0009831 (previously applied) . As mentioned in the above 103 rejection, all of the limitations of claims 7, 9, 11, 15-18 and 21-26 are taught by the combination of Ma and the ‘296 publication. The combination of references does not specifically teach wherein the effective amount of the focal adhesion kinase inhibitor is from 30 to 100 micrograms/g tissue by weight (claim 19). The ‘831 publication teaches compounds for use for preventing or treating diseases that may be modulated by inhibitors such as kinase proteins (abstract). Kinase proteins belong to the group including FAK and treating or preventing diseases modulated by the inhibition of such kinase proteins is taught ([0003], [0026]). The dose employed will be determined by physical and depends on the desired therapeutic effect, the route of administration and the duration of treatment. Adult doses are generally from 0.001 to about 50 mg/kg body weight per day ([0703]-[0704]), leading to 0.001-50 ug/g. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known dosing ranges of FAK inhibitor compounds for the hydrogels taught by Ma as the ‘831 publication kinase inhibitors taught to be used in dosage range, wherein the range is taught to be an optimizable parameter. One of ordinary skill in the art before the filing date of the claimed invention would have a motivation to use known concentrations of kinase inhibiting compounds to be used and optimize as the ‘831 publication teaches known amounts of kinase initiators and teaches that the dosage amount is determined by a physician. That being said and in lieu of objective evidence of unexpected results, the dosage can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious . Double Patenting 08-33 AIA 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. 08-35 AIA Claim 7, 9, 11, 15-16 and 21-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 3-20 of copending Application No. 18/288,652 (reference application) in view of Ma . Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the ‘940 patent are directed to placing a composition so FAK inhibitor and pullulan porous scaffold at a wound site to release the FAK inhibitor locally, wherein the wound site is a burn and the FAK inhibitor is controlled release, thus teaching the same active steps of the same composition, thus would necessarily result in functions of the FAK inhibitor, as claimed thus anticipating the instant claims. The ‘652 publication does specifically teak FAK inhibitor selected form the group which includes VS-6062. Ma teaching FAK inhibitor can be attenuate scar development. The use of Pullulan collagen-based hydrogel to delivery FAKI to excisional and burn wounds in mice. Drug-laden hydrogel was developed for rapid and sustained release of FAKI for treatment of burn wounds and excisional wounds. FAKI via pullulan collagen hydrogel accelerated wound healing and reduced collagen disposition and activation of scar-forming myofibroblasts in both wound healing models (abstract). FAKI is taught to be incorporated into the porous hydrogel, which enabled slow and sustained release of the FAKI to the wound environment over a few days (page 2453, first column, first paragraph). Reduced inflammation and fibrosis in an incision HTS model using FAK knockout mice is taught (page 2452, second column, second paragraph, page 2456, second column, last paragraph). Ma teaches VS-6062 (page 2455, first column, first paragraph). It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known FAK inhibitors to treat wounds in pullan-collagen matrix as taught by Ma for the wound treating compositions comprising pullan and FAK inhibitor as taught by the ’652 publication as MA teaches specific FAK inhibitors known to treat wounds in pullan collagen . This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Response to Arguments : Applicant’s arguments have been fully considered and are not deemed to be persuasive. 112(b) : Applicant argues claim 19 has been amended to recite wherein the effective amount of the focal adhesion kinase inhibitor delivered to the wounded tissue is from 30 to 100 micrograms per gram of wounded tissue by weight. The specification express support in that the actual dose delivered to the wound was tested on porcine fresh wounds from 30-100 microG/g tissue weight. In response, claim 19 is directed to wherein the effective amount of the focal adhesion kinase inhibitor is from 30 to 100 micrograms per gram of wounded tissue by weight. It is unclear where tissue starts and wounded tissue ends, thus leading to unclear concentration. 103 : Ma and the ‘296 publication (Walmsley) Applicant argues the claims methods are not directly merely to wound healing or scar reduction but specifically requires as amended reducing fibrosis while inducing regenerative cell population to promote skin regeneration including secondary structures in a large mammal. This is fundamentally different biological outcome from the accelerated wound closure and decreased collagen deposition reported by Ma. In response, Ma teaches that the active step of disposing the claimed composition and releasing the FAKI and thus would necessarily result in reducing fibrosis while inducing regenerative cell population to promote skin regeneration, including regeneration of secondary structures and healing the wounded tissue. The limitation of wherein the FAK inhibitor is the elected VS-6062 is met by Ma teaching VS-6062. Ma teaches the wound is taught to use silicone rings to prevent wound contracture (primary means of rodent wound healing) but to allow the wound to closely re-epithelization (similar to human wounds (page 2458, second column, last paragraph, page 2452, second column, last paragraph, page 2453, second column, second paragraph). Thus Ma teaches the desire to treat humans and mimicking human wound healing. Applicant argues Ma results are limited to reduced fibrinogenic activity, reduced collagen deposition and alpha-SMA expression and does not disclose or suggest tissue regeneration or the induction of regenerative cell populations. The ‘296 publication active agents are macrophages and monocyte progenitors, entirely different from FAK inhibitors, which are small molecules. The therapeutic effects sought by the ‘296 publication are different from the present method and provide not motivation regarding FAK inhibitor, mechanotransduction or induction of regenerative cell populations. In response, Ma teaches FAKI therapy via pullan-collagen hydrogel was shown it be effective in reducing scar formation while promoting healing of excisional and burn wounds in mouse models. Results of this study enable the translation of FAKI scar reduction therapy in highly translational preclinical large animal model and potential human clinical trials (page 2457, second column, first paragraph). The wound is taught to use silicone rings to prevent wound contracture (primary means of rodent wound healing) but to allow the wound to closely re-epithelization (similar to human wounds) (page 2458, second column, last paragraph, page 2452, second column, last paragraph, page 2453, second column, second paragraph). Thus Ma teaches the desire to treat humans and mimicking human wound healing. The ‘296 publication teaches compositions for enhanced healing of wounds, e.g. cutaneous wounds by application of a scaffold comprising a hydrogel film (abstract). The hydrogel is taught to be pullulan and collagen ([0011]-[0012]). The composition is taught to include porous wound dressings and the like used to treat dermal tissues including burn wounds [0075]. Treatment is taught to be applied to wound of a subject wherein the subject includes mice, pigs, rate and primates including humans [0081]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to apply the composition of Ma to human as the ‘296 publication teaches mammals to be treated include mice and humans. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as Ma and the ‘296 publication are both directed to compositions including pullulan-collagen scaffolds used to treat burns, thus it would be obvious to use the compositions of Ma to treat the patient population disclosed by the ‘296 publication. Applicant agues the present specification discloses, for the first time, that mechanical stress and cellular mechanotransduction signaling pathways are critically important factors distinguishing large mammal wound healing from that of organisms such as mice. A key feature that distinguishes model organisms from humans and other large mammals is mass which leads to increasing mechanical properties of their tissues. Applicant is the first to discover that disrupting the functional relationship between mass and force can erase the evolutionary tradeoff between organisms’ complexity and regenerative capability. In response, Applicant appears to be arguing unexpected results however has present not factual evidence. Applicant points to [0065] which is not factual evidence wherein actual evidence is required. The instant specification provides data comparing wounds, wounds with hydrogel and wounds with hydrogel and a specific FAK inhibitor. This however is not found persuasive ans Ma teaches wound healing increases with the use of FAK inhibitor, thus the result are not considered unexpected. Ma teaches that the active step of disposing the claimed composition and releasing the FAKI and thus would necessarily result in reducing fibrosis while inducing regenerative cell population to promote skin regeneration and healing the wounded tissue. Applicant argues Ma acknowledges that its results are limited to mouse models and human trials represent a future goal. The use of splints to mimic human wound healing implicitly acknowledges the fundamental different between mouse and human wound healing. Preclinical studies are required in ode to establish or identify safety pharmacokinetic and proof of concept, dose selection and mechanism of action, otherwise drug would go form animal directly to formal human clinical trials. The Examiner has not provided any evidence that counters the expert acknowledge innovations and inventive contribution of Applicants have presented. In response, Ma teaches FAKI therapy via pullan-collagen hydrogel was shown it be effective in reducing scar formation while promoting healing of excisional and burn wounds in mouse models. Results of this study enable the translation of FAKI scar reduction therapy in highly translational preclinical large animal model and potential human clinical trials (page 2457, second column, first paragraph). The wound is taught to use silicone rings to prevent wound contracture (primary means of rodent wound healing) but to allow the wound to closely re-epithelization (similar to human wounds (page 2458, second column, last paragraph, page 2452, second column, last paragraph, page 2453, second column, second paragraph). Thus Ma teaches the desire to treat humans and mimicking human wound healing. The ‘296 publication teaches compositions for enhanced healing of wounds, e.g. cutaneous wounds by application of a scaffold comprising a hydrogel film (abstract). The hydrogel is taught to be pullulan and collagen ([0011]-[0012]). The composition is taught to include porous wound dressings and the like used to treat dermal tissues including burn wounds [0075]. Treatment is taught to be applied to wound of a subject wherein the subject includes mice, pigs, rate and primates including humans [0081]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to apply the composition of Ma to human as the ‘296 publication teaches mammals to be treated include mice and humans. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as Ma and the ‘296 publication are both directed to compristion including pullulan-collagen scaffolds used to treat burns, thus it would be obvious to use the compositions of Ma to treat the patient population disclosed by the ‘296 publication. Applicant argues the specification describes experiments in which FAKI-releasing pullulan-collagen hydrogel were applied to deep partial thickness excisional wounds on lateral dorsum of red Durcoc pigs, a large animal widely considered the most similar to humans in terms of skin physiology and cutaneous wound healing. Dramatically accelerated wound closure in those treated with FAKI hydrogel. While Ma reported that FAKI accelerated wound closure by 3 days, the magnitude of acceleration in pigs, more than 10 days was unexpected. Normal skin architecture resulting in normal appearing skin in treated pig wounds. Applicant unexpectedly found that wounds treated with FAKI exhibited tissue properties similar to that of unwounded skin. Regenerative of secondary structures including hair follicles. Regeneration of intradermal adipocytes. The method is specifically directed to inducing regenerative cell populations and promoting skin regeneration in large mammals, precisely the results demonstrate in the specification. Ma only teaches that FAK inhibitor is beneficial toward improving the physical integrity of healing skin in mic burn wounds treated with FAKI showed accelerated wound closure. In response, Ma teaches FAKI therapy via pullan-collagen hydrogel was shown it be effective in reducing scar formation while promoting healing of excisional and burn wounds in mouse models. Results of this study enable the translation of FAKI scar reduction therapy in highly translational preclinical large animal model and potential human clinical trials (page 2457, second column, first paragraph). The wound is taught to use silicone rings to prevent wound contracture (primary means of rodent wound healing) but to allow the wound to closely re-epithelization (similar to human wounds (page 2458, second column, last paragraph, page 2452, second column, last paragraph, page 2453, second column, second paragraph). Thus Ma teaches the desire to treat humans and mimicking human wound healing. The ‘296 publication teaches compositions for enhanced healing of wounds, e.g. cutaneous wounds by application of a scaffold comprising a hydrogel film (abstract). The hydrogel is taught to be pullulan and collagen ([0011]-[0012]). The composition is taught to include porous wound dressings and the like used to treat dermal tissues including burn wounds [0075]. Treatment is taught to be applied to wound of a subject wherein the subject includes mice, pigs, rate and primates including humans [0081]. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to apply the composition of Ma to human as the ‘296 publication teaches mammals to be treated include mice and humans. Thus Ma teaches administration of the same composition with the desire for human use and wound healing as a result. Thus the specific wound healing in the instant specification is not unexpected, rather an expected result of administration of the compositions as taught by Ma. Further Applicant has tested only a single compound at a single concentration, and thus is not commensurate in scope with the instant claims and additionally only tests the composition in pigs, providing no comparison data. Wound healing is expected as discussed via Ma, wherein Applicant’s data is a comparison between a control, a hydrogel only and the drug containing hydrogel, thus the superior wound healing in the use of FAKI is expected in comparison to its absence and does not demonstrate unexpected results. Applicant argues the ‘296 publication is directed macrophage or monocyte laden hydrogels for wound healing. It is not analogous to Ma or the present claims. The cells have different lineages and functions. The ‘296 publication provides no teachings related to promoting tissue healing while reducing fibrosis. Even is the ‘296 publication taught that is monocyte and macrophage compositions could have an effect on large mammals no one of skill in this field would somehow think that the ‘296 publication has any applicability to use FAKI on a completely different cell group, i.e. fibroblasts. Thus the ‘296 publication does not fill in the gaps of Ma. In response, Ma teaches FAKI therapy via pullan-collagen hydrogel was shown it be effective in reducing scar formation while promoting healing of excisional and burn wounds in mouse models. Results of this study enable the translation of FAKI scar reduction therapy in highly translational preclinical large animal model and potential human clinical trials (page 2457, second column, first paragraph). The ‘296 publication teaches compositions for enhanced healing of wounds, e.g. cutaneous wounds by application of a scaffold comprising a hydrogel film (abstract). The hydrogel is taught to be pullulan and collagen ([0011]-[0012]). The composition is taught to include porous wound dressings and the like used to treat dermal tissues including burn wounds [0075]. Treatment is taught to be applied to wound of a subject wherein the subject includes mice, pigs, rate and primates including humans [0081]. Thus Ma teaches the use of the claimed compositions to treat burns with the desire to treat human and the ‘296 publication provides an expectation of success in the use of the same hydrogel used to treat the same injury, burns, may be used in humans. One would look to the ‘296 publication as it is directed to the same hydrogel to treat the same injury in overlapping subjects. Applicant argues hindsight reasoning. As for the assertion that the rejection is based on hindsight, as noted in MPEP 2145, any obviousness rejection is in a sense necessarily a reconstruction based on hindsight reasoning and is not improper if it takes into account only knowledge within the level of ordinary skill in the art at the time the claimed invention was made. Applicants have provided no evidence that the rejection is not based on knowledge available to those of ordinary skill in the art. Applicant argues the inherent reasoning for claims 21-26 is incorrect. The claimed method is specifically directed to large mammals, not mice. The specification demonstrates that effects of FAK inhibition are materially different in large mammals compared to mice, see 62-65. Thus it would not necessarily result. The biological effects recited in claim 21-26 were demonstrated through experiments in porcine tissue and human dermal fibroblast, not merely inferred from mouse data. These genomic finds were confirmed at the protein level in porcine tissue where immunofluorescent staining demonstrated decreased expression of alpha SMA, Collagen I and Collagen III in FAKI treated wounds. In response, Ma teaches that the active step of disposing the claimed composition and releasing the FAKI and thus would necessarily result in functions of the FAK inhibitor, as claimed. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya , 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Applicant argues the ‘831 publication teaches mg/kg body weight reflecting total systemic exposure via oral administration for cancer treatment. The dosage recited in claim 19 as amended is of wounded tissue by weight and refers to local concentration. The dosage parameters are fundamentally different and not interchangeable. The Examiner’s characterization of dosage as a result effective variable subject to routine optimization is inapposite. The oral cancer treatment des not disclose the general conditions for local wound tissue concentration. Applicant points to [0042] and Figure 6B. In response, Applicant is referred to the newly applied 112(b) rejection above regarding concentration and wounded tissue. The ‘831 publication teaches the dosing of FAK for treating diseases to be determined based on desired therapeutic effects, and thus an optimizable parameter. Applicant has presented no unexpected results regarding the concentrations used. In lieu of objective evidence of unexpected results, the dosage can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious. Applicant points to [0042] and Figure 6B to demonstrate claimed range testing, however the results are regarding 150 M and 1.5 mM in DMSO and PEG. This is not commensurate in scope or comparative compared to the claimed range of 30-100 micrograms per gram of wounded tissue by weight. Double Patenting : Applicant requests the rejection be held in abeyance until there is an indication of allowable subject matter. In response, Applicant has presented no substantive arguments, thus the rejection is maintained for reasons of record. Conclusion No claims are allowed. 07-40 AIA Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL . See MPEP § 706.07(a). 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. Examiner Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /LYNDSEY M BECKHARDT/Examiner, Art Unit 1613 /BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613 Application/Control Number: 17/914,134 Page 2 Art Unit: 1613 Application/Control Number: 17/914,134 Page 3 Art Unit: 1613 Application/Control Number: 17/914,134 Page 4 Art Unit: 1613 Application/Control Number: 17/914,134 Page 5 Art Unit: 1613 Application/Control Number: 17/914,134 Page 6 Art Unit: 1613 Application/Control Number: 17/914,134 Page 7 Art Unit: 1613 Application/Control Number: 17/914,134 Page 8 Art Unit: 1613 Application/Control Number: 17/914,134 Page 9 Art Unit: 1613 Application/Control Number: 17/914,134 Page 10 Art Unit: 1613 Application/Control Number: 17/914,134 Page 11 Art Unit: 1613 Application/Control Number: 17/914,134 Page 12 Art Unit: 1613 Application/Control Number: 17/914,134 Page 13 Art Unit: 1613 Application/Control Number: 17/914,134 Page 14 Art Unit: 1613 Application/Control Number: 17/914,134 Page 15 Art Unit: 1613 Application/Control Number: 17/914,134 Page 16 Art Unit: 1613 Application/Control Number: 17/914,134 Page 17 Art Unit: 1613 Application/Control Number: 17/914,134 Page 18 Art Unit: 1613 Application/Control Number: 17/914,134 Page 19 Art Unit: 1613 Application/Control Number: 17/914,134 Page 20 Art Unit: 1613 Application/Control Number: 17/914,134 Page 21 Art Unit: 1613 Application/Control Number: 17/914,134 Page 22 Art Unit: 1613 Application/Control Number: 17/914,134 Page 23 Art Unit: 1613 Application/Control Number: 17/914,134 Page 24 Art Unit: 1613 Application/Control Number: 17/914,134 Page 25 Art Unit: 1613
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