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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 15, 2026 has been entered.
The amendment filed January 15, 2026 has been entered. Claims 5 and 9 have been amended and claims 1-4 and 6 are cancelled. This application is a 371 of PCT/US2019/044785 filed 08/02/2019 and claims benefit to US provisional applications 62/822,193 filed 03/22/2019 and 62/714,114 filed 08/03/2018.
Applicant’s arguments filed January 15, 2026 with respect to claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claims 5 and 7-19 are pending in this application.
Claim Objections
Claims 5 and 9 are objected to because of the following informalities:
In claim 5 the phrase “a HIF prolyl hydroxylase domain” should read “a HIF prolyl hydroxylase domain inhibitor”.
In claims 5 and 9 HIF should be defined.
In claim 9 the phrase “car” should read “scar”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (a)
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.
Claims 5 and 7-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The specification, while being enabling for the reduction of scar collagen abundance, scar width, and scar tissue contracture during scar formation does not reasonably provide enablement for the reduction of scar collagen abundance, scar width, and scar tissue contracture of a scar that has already healed and re-epithelialized. The specification does not enable any person skilled in the art to which is pertains, or with which it is most clear connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art. All of the factors have been considered with regard to the claim, with the most relevant factors discussed below:
(1& 2)The breadth of the claims and nature of the invention: The claims are directed to a method for reducing scar collagen abundance, scar width, and scar tissue contracture comprising administering a compound that is an HIF prolyl hydroxylase inhibitor and/or a mast cell stabilizer in a subject having a scar, wherein the scar has already healed and re-epithelialized.
(3) The state of the prior art: While there are publications that describe methods of reducing scar formation during the healing process comprising administering a compound that is HIF prolyl hydroxylase inhibitor and/or a mast cell stabilizer, there is no evidence in the prior art that the claimed composition would reduce the scar after it is already healed.
Hong (Advances in Wound Care, 2014, cited on PTO-892) teaches hypoxia-inducible factor-1 (HIF-1), as the master regulator of oxygen homeostasis, is an important determinant of healing outcomes (abstract). HIF-1 contributes to all stages of wound healing through its role in cell migration, cell survival under hypoxic conditions, cell division, growth factor release, and matrix synthesis throughout the healing process (abstract). Hong teaches positive regulators of HIF-1, such as prolyl-4-hydroxylase inhibitors, have been shown to be beneficial in enhancing diabetic ischemic wound closure and are currently undergoing clinical trials for treatment of several human-ischemia-based conditions (abstract). According to Hong, Scar formation is part of the wound healing process (pg. 391, figure 1). Hong teaches hypertrophic scars develop after deep or extensive cutaneous insults, such as burns and surgical incisions, and can be treated through grafting and surgical corrections (pg. 396, col. 1, para. 1). Hong teaches wound care strategies currently available to patients remain far from ideal, owing mostly to our limited understanding of the complex mechanics involved in the healing process (pg. 396, col. 2, last para.). A better understanding of the complex role of hypoxia in scarring tissues and chronic wounds will aid in the development of pharmaceutical agents that can redress the detrimental outcomes often seen in insufficient repair and scarring (pg. 396, col. 2, last para.).
Tang (Cell Physiol. Biochem., 2018, cited in previous action) 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.).
Chen (PLoS ONE, 2014, IDS filed February 10, 2021) 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 (IJPRD, 2013, cited in previous action), 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). 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).
Larouche (Advances in Wound Care, July, 2018, cited in previous action) 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). 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).
Thus, in short, the art recognizes treatment including administering therapeutic compositions in the reduction of a scar when administered during wound repair/healing, but does not recognize the ability to reduce a scar once healed.
(4 & 6) The amount of direction provided by the inventor and the existence of working examples: Applicant has not provided examples that demonstrate that the composition claimed is effective at reducing the scar after it is already healed. The instant specification provides dual therapeutic approach to targeting both mast cells and fibroblasts with a mast cell stabilizer and a HIF prolyl hydroxylase inhibitor delivered locally to an incision to reduce collagen abundance, width, and scar tissue contracture (pg. 29, para. 00149). The instant specification demonstrates that mast cells contribute to incisional wound healing and scar formation (pg. 27, para. 00140). The instant specification demonstrates treatment with ketotifen, a mast cell stabilizer, lessened the inflammatory response to incisional wound, decreased scar width, and decreased scar collagen abundance in a wound scar compared to untreated wound scar (pg. 28, para. 00144). The instant specification states that during the inflammatory phase of wound healing, TF-B is secreted and activates fibroblasts to produce SMA, leading to scar contracture (pg. 29, para. 00147). The instant specification demonstrates that a HIF prolyl hydroxylase inhibitor decreases the abundance of TF-B induced SMA in fibroblasts (pg. 29, para. 00147). In short, the instant specification demonstrates administration of the claimed compositions comprising HIF prolyl hydroxylase inhibitor and/or mast cell stabilizer during the healing/scar formation process lead to reduction in the healed scar properties. Applicant has not demonstrated that when the composition is administered to a subject a scar that is already healed, it would reduce the scar tissue contracture, scar width, and scar collagen abundance.
(5) The level of predictability in the art: The prior art does not teach a method of reducing scar tissue contracture, scar width, and scar collagen abundance in a scar that is already healed by administering a therapeutic composition. Although some methods may aid in the reduction of a scar via treatment during the wound repair/healing process/scar formation or may surgically treat or use skin grafts to treat a scar, there is nothing in the prior art that indicates that reduction once a scar is formed is possible via the administration of therapeutic composition. The resulting impact on a scar that is already healed would not be predictable to a person of ordinary skill in the art.
(7) The quantity of experimentation: Neither the instant specification nor the state of the art have demonstrated how therapeutic compositions, such as the composition claimed, can reduce scar tissue contracture, scar width, and scar collagen abundance in a scar that is already healed. An undetermined number of experimental factors utilizing a composition and its method for treating a scar that is already healed would have to be resolved by the practitioner and/or the patient for the following reasons: the factors are not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
(8) The level of skill in the art: The level of skill in the art would be high, mostly likely at the Ph.D. /MD level.
Therefore, other than proposing an initial hypothesis, the entire burden of research
involved in utilizing the compositions claimed to reduce a scar that is already healed would fall on the shoulders of the skilled artisan attempting to practice the claimed invention, presenting an undue burden of unpredictable experimentation.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a
reward for search, but compensation for its successful conclusion.” And “patent protection is
granted in return for an enabling disclosure of an invention, not for vague intimations of general
ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention without undue experimentation.
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.
Claim 16 is 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 claim 16: Claim 16, which depends from claim 9 and recites, “wherein the mast cell stabilizer is administered locally to an incision site.”. According the instant specification administration to an incision cite is where the scar is expected to form (pg. 10, para. 0053). However claim 9 recites administration to “a subject having a scar, wherein the scar is has already healed, and re-epithelialzed”. Thus it is unclear whether the incision site is referring to the site of the scar, or is referring to a separate incision prior to healing that is unrelated to the scar the subject has.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 16: Claim 16, which depends from claim 9 and recites, “wherein the mast cell stabilizer is administered locally to an incision site.”. According the instant specification administration to an incision cite is where the scar is expected to form (pg. 10, para. 0053). However claim 9 recites administration to “a subject having a scar, wherein the scar is has already healed, and re-epithelialized”. The phrase incision site implies that the scar is not healed, thus claim 16 expands, rather than limits claim 16.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
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