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 .
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.
Response to Amendment
The amendment filed October 16, 2025 has been entered. Claims 5 and 9 have been amended and claims 1-4 and 6 are cancelled. Applicant’s cancellation of claims 1-3 have rendered the corresponding rejections moot. Thus, these rejections are hereby withdrawn.
Applicant’s arguments filed October 16, 2025 were fully considered but are not persuasive. Modified/New rejections necessitated by Applicant’s amendment and response to arguments are addressed below.
Claims 5 and 7-19 are pending in this application.
New Claim Objections
Claim 5 is objected to because of the following informalities:
In claim 5, the phrase “in amount effective to” should read “in effective amounts to” as in claim 9, or “in an amount effective to”.
Appropriate correction is required.
New Claim Rejections - 35 USC § 112 (b)
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.
Claims 5 and 7-19 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.
Regarding claims 5 and 7-19: The term “adequately” in claims 5 and 9 is a relative term which renders the claim indefinite. The term “adequately” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “adequately” is subjective and a person of ordinary skill in the art would be unable to ascertain what constitutes an adequate amount of healing encompassed by the method. Claims 7-8 and 10-19 which depend from claims 5 and 9 respectively, are similarly rejected.
Regarding claims 5 and 7-19: Claims 5 and 9 recite inter alia, “….to reduce collagen abundance, scar width, and scar tissue contracture of a scar that has already been re-epithelialized and adequately healed”. It is unclear whether the claims are merely describing an eventual outcome of the method, whereby the reduction in collagen/scar width/scar tissue contracture results from treating a wound, or wherein the claims are limiting wherein the method is applied to a scar. For example, application to an open wound would result in reducing these metrics in a scar that has already been epithelialized and adequately healed. According to the instant specification the active agent is administered continuously and locally during wound healing of an incision, wherein the eventual scar width and collagen amount is reduced (pg. 28, paras. 00143-00144). The specification states that the invention delivers to an incision (pg. 29, para. 00149). Additionally, according to the instant specification, re-epithelialization and adequate healing is solely relevant to scar tissue contracture, but not necessarily collagen and scar width (pg. 7, para. 0040), but as written it is unclear whether the limitations of scar collagen abundance and scar width are associated with a scar that has already been re-epithelialized and adequately healed. Given the multiple interpretations, the scope of the claims are unclear and thus rendered indefinite. Claims 7-8 and 10-19 which depend from claims 5 and 9 respectively, are similarly rejected.
Maintained Claim Rejections - 35 USC § 102
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 5 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang (Cell Physiol. Biochem., 2018, cited in previous action).
Regarding claims 5 and 7-8: Tang teaches the administration of FG-4592 intraperitoneally (i.e. systemically) for wound healing in mice (abstract, pg. 2463, paras. 4-6). Tang teaches that FG-4592 exerts its effects through HIF-1a stabilization (pg. 2465, col. 1, para. 2). Tang teaches FG-4592 accelerated wound healing (pg. 2465, last para.). The wound closure time was measured, but Tang does not disclose information pertaining to scar collagen abundance, scar width, and scar tissue contracture as claimed. However, on page 29 of the instant specification, applicant describes that during the inflammatory phase of wound healing, the cytokine transforming growth factor β (TGF-β) is secreted and can activate fibroblasts to produce SMA (para. 00147). Applicant further describes that PHD inhibitors, such as RXD (i.e. FG-4592) decrease scar contracture by inhibiting the abundance of TGF-β induced SMA in fibroblasts (para. 00147). Although, Tang does not explicitly state wherein scar collagen abundance, scar width, and scar tissue contracture of a scar that has already been re-epithelialized and adequately healed is reduced, these are inherent properties of administering FG-4592 for inducing wound healing. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999, see MPEP 2122 (I)).
Modified 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.
Claims 9-19 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (PLoS ONE, 2014, IDS filed February 10, 2021) in view of Sowjanya (IJPRD, 2013, cited in previous action), Larouche (Advances in Wound Care, July, 2018, cited in previous action) and Silver (US 2009/0318545, cited in previous action) and Tang (Cell Physiol. Biochem., 2018, cited in previous action) as applied to claims 5 and 7-8 above.
Regarding claims 9-10 and 14-19: Chen teaches the administration of disodium cromoglycate (DSCG) for the treatment of wounds in mice (abstract, pg. 3, col. 1, para. 2). DSCG is the disodium salt of cromoglicic acid. According to Sowjana, cromoglicic acid is known in the art as a mast cell stabilizer that is commonly marketed as the sodium salt (pgs. 112-113, bridging para.). The disodium salt of is also referred to as sodium cromoglycate (pg. 113, col. 1, fig. 1). Thus, cromoglicic acid and DSCG are equivalents for the purpose of acting as a mast cell stabilizer (See MPEP 2144.06). To assess the effects of mast cell degranulation of wound repair, mice were injected intraperitoneally with DSCG (pg. 2, col. 1, para. 5).Chen teaches administration of DSCG inhibits mast cell degranulation and reduces scar width of wounds (pg. 5, col. 1, para. 1, pg. 6, col. 2, para. 1). Chen inhibition of mast cell degranulation with DSCG resulted in a wound bed with more organized collagen, and with architecture more similar to normal skin (pg. 5, cols. 1-2, bridging para., pg. 8, col. 2, para. 2). Chen teaches that DSCG treatment reduces the immediate inflammatory response in wounds (pg. 8, col. 1, para. 1). According to the instant specification, administration of a mast cell stabilizer, such as cromoglicic acid, results in decreased collagen abundance and scar tissue contracture (pg. 2, para. 0008, pg. 7, para. 0041). Although, Chen does not explicitly state wherein scar collagen abundance and scar tissue contracture in a scar that has already been re-epithelialized and adequately healed is reduced, wherein Chen teaches the administration of a mast cell stabilizer for the reduction of scarring in wounded mice, these are properties that necessarily flow from the teachings of Chen. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999, see MPEP 2122 (I)).
Chen does not teach wherein the mast cell stabilizer is administered locally to a wound. Chen does not teach wherein the mast cell stabilizer is ketotifen.
However, Larouche teaches mast cells can be specifically targeted to reduce scar formation by administering stabilizers to prevent de-granulation, such as cromoglicic acid and ketotifen (pg. 224, col. 1, para. 1). Wherein both cromoglicic acid and ketotifen are recognized in the art as mast cell stabilizers capable of reducing scar formation, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Larouche teaches that typically therapies for wound resolution or scar prevention are delivered via injections or applied topically to the wound site (pg. 210, col. 2, para. 2). Additionally, Silver teaches a method for treating an ophthalmic retinal vascular permeability, angiogenic or fibroproliferative disease comprising administering a composition containing a mast cell stabilizer, such as ketotifen or cromolyn (pg. 1, abstract, pg. 2, paras. 0017-0018). According to the instant specification cromolyn is synonymous with cromoglicic acid (pg. 9, para. 0051). The ophthalmic abnormal retinal vascular permeability, angiogenic or fibroproliferative disease includes scarring of the retina (pg. 1, para. 0013). In some embodiments the composition is administered locally to the affected tissues via a contact lens containing the composition, or via a topical solution or gel (pg. 1-2, para. 0015). Silver also teaches the therapeutic agents may be formulated for direct application to a target area (pg. 8, para 0100). The therapeutic agents can be delivered via patches or bandages for dermal administration (pg. 8, para 0100). when local administration is employed the dosages used can be lower than the dosage typically administered systemically for that composition (pg. 2, para. 0019). Moreover, it may also be useful to continuously administer the composition when performing the method describe herein (pg. 2, para. 0019).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Chen by administering a mast cell stabilizer, such as cromoglicic acid or ketotifen, locally to a wound for the purpose of reducing scarring in the wound of a subject. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art recognizes mast cell stabilizers as suitable treatments for scarring, local administration for wound healing is a routine practice in the art, and local administration can result in lower doses being required compared to systemic administration.
As discussed above, the prior art teaches and/or renders obvious both a method of administering mast cell stabilizer ketotifen and a method of administering Roxadustat (RXD) for the purpose of accelerating reducing scarring or accelerating the wound healing process in a subject. The prior art does not teach wherein the two agents are administered together for the purpose of reducing scarring in a subject. However, wherein both approaches target different pathways for the same purpose, it would have been prima facie obvious to one of ordinary skill in the art to combine the methods into a combination therapy for the purpose of reducing scarring in a subject in need thereof.
Regarding claims 11-13: The prior art does not teach a method wherein the mast cell stabilizer and PHD inhibitor are administered consecutively, separately, or simultaneously. However, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum method of administration by routine experimentation (See MPEP 2144.05). It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions” (See MPEP 2144.05).
Response to Arguments
Applicant’s arguments filed October 16, 2025 have been fully considered but are not persuasive.
On pages 5-6 of Applicant’s response, Applicant argues that Tang does not teach the newly added limitations of reducing scar collagen abundance, scar width, and scar tissue contracture of a scar that has re-epithelialized and adequately healed (bridging para.). Applicant argues that Tang is focused on the study of acute hypoxia and its effect on epidermal stem cells. On page 6 of Applicant’s response, Applicant argues the method of Tang is limited to wound closure, and does not study re-epithelialized tissue. Applicant argues a person of ordinary skill in the art would not recognize the benefit past the point of re-epithelialization. On page 6 of Applicant’s remarks, Applicant describes the process by which EpSCs are activated and recruited from different skin regions during wound healing in response to a cutaneous wound (last para.). On page 7 of Applicant’s response, Applicant argues that wound healing is a highly conserved mechanism that includes well defined processes and cell types. Applicant argues that scar formation, as a part of wound healing, occurs (para. 1). Thus, on pages 6-7 of Applicant’s remarks, Applicant is arguing that the present invention is directed towards scar formation which occurs after re-epithelialization during a wound healing process (bridging paras.). Applicant argues that scar formation occurs after re-epithelialization and has different mechanisms which would not be anticipated or rendered obvious over the cited art.
However, the Examiner notes that the previous claim set were directed towards reducing scar collagen abundance, scar width, and scar tissue contracture, but did not specify that the scar has already been epithelialized and adequately healed. According to the instant specification, the instant method is applied during the entire wound healing process wherein the claimed effect (decreasing collagen, scar width) occurs as a result (pg. 28, paras. 00143-00146). Additionally, according to the instant specification, re-epithelialization and adequate healing is solely relevant to scar tissue contracture, but not necessarily collagen and scar width (pg. 7, para. 0040). "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999, see MPEP 2122 (I)). Thus, wherein the active agent in the art is similarly applied during the wound healing process, it necessarily results in a scar that has already re-epithelialized and adequately healed having reduced scar collagen abundance, scar width, and scar tissue contracture. See 112(b) issues above. Chen and Tang establish that mast cell stabilizers and HIF-1α both are advantageous in wound healing (abstracts), thereby rendering the claimed method obvious, absent a showing of unexpected results.
On pages 8-9 of Applicant’s remarks, Applicant repeats the argument above, that the art does not teach or suggest administering the combination therapy to reduce scar collagen abundance, scar width, and scar tissue contracture of a scar that has already been re-epithelialized and adequately healed.
See response to arguments above.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The rejections above are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
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.
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/S.L.G./Examiner, Art Unit 1693
/ERIC OLSON/Primary Examiner, Art Unit 1693
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