DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment and response filed on 6/17/2026 have been received and entered into the case. Claims 2, 6, 10, and 14 have been canceled. Claims 1, 3-5, 7-9, 11-13, and 15-20 are pending, Claim 20 has been withdrawn, and Claims 1, 3-5, 7-9, 11-13, and 15-19 have been considered on the merits, insofar as they read on the elected species of bromelain (first protease), ficain (second protease), actinidain (third protease), asclepain (fourth protease), and Interleukin-1β (protein). All arguments have been fully considered.
Withdrawn Rejections
Rejections of Claims 1, 3 and 17-19 under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Kling et al (US 2015/0297687 A1; 10/22/2015.) are withdrawn in view of applicant’s amendments.
Rejections of Claims 4-5, 7-9, 11-13, and 15-16 under 35 U.S.C. 103 as being unpatentable over Kling et al (US 2015/0297687 A1; 10/22/2015.) in view of Schultz et al (Wounds International. 2017;1-6.) are withdrawn in view of applicant’s amendments.
Rejections of Claims 2, 6, 10, and 14 under 35 U.S.C. 103 as being unpatentable over Kling et al (US 2015/0297687 A1; 10/22/2015.) in view of Schmalz (https://awakeninghealth.ca/physiological-effects-of-inflammation. 2022;1-2.) are withdrawn in view of applicant’s amendments.
Claim Rejections - 35 USC § 112
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 1, 3-5, 7-9, 11-13, and 15-19 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 pre-AIA the applicant regards as the invention.
Claim 1, line 6-7, recites the limitation “the first protease composition”. There is insufficient antecedent basis for this limitation in the claim. Applicant is required to amend the claim so as to provide proper antecedent basis for this language in the claim.
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 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 of this title, 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 1, 3-5, 7-9, 11-13, and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kling et al (US 2015/0297687 A1; 10/22/2015.) in view of Schultz et al (Wounds International. 2017;1-6.) and Schmalz (https://awakeninghealth.ca/physiological-effects-of-inflammation. 2022;1-2.).
The instant claims recite a method to promote tissue repair and wound healing, the method comprising: applying a protease composition to an area of skin during a first wound healing stage, the first wound healing stage being selected from the group consisting of a hemostasis stage, an inflammatory stage, a proliferative stage, and a remodeling stage; wherein the first protease composition comprises one or more proteases; modulating, by the first protease composition, at least one of a wound-related protein or an inflammation-related protein; and treating the area of skin for a first period of time in a range of 6 to 72 hours.
Kling teaches a method for modulating the protein profile of a tissue or its surrounding environment to promote the repair of a damaged tissue, or one that is otherwise compromised by disease or injury, by administering a composition containing proteases to the affected area (para 0013), wherein the protease can modulate the action or level of at least one protein, and said protein is a wound-related protein or an inflammation-related protein (para 0014). Said proteases are useful for wound healing, reducing inflammation (an inflammatory stage) and promoting development of healthy skin (a proliferative stage / a remodeling stage) (para 0026, 0039), and promote wound healing and prevent or treat skin problems (para 0038). Said proteases include bromelain, ficain, actinidain, and asclepain (para 0032). Wound-related protein include Interleukin-1β (IL-β) (para 0018). Inflammation-related protein include IL-β (para 0019). One of skill in the art can choose an appropriate protease or combination of proteases to achieve the quality and quantity of modulation desired (para 0024-0025, 0028, 0038). Administration of the composition comprises proteases diminishes the rate of itching (para 0021). Said proteases can be formulated into a therapeutic composition including a solution, a skin covering or dressing that provide slow or timed release of the proteases into a wound (para 0039).
Kling does not teach the method comprises a first protease composition (claim 1), a second protease composition including ficain that is applied subsequent to the first wound healing stage (claims 5 & 7), a third protease composition including actinidain that is applied subsequent to the first wound healing stage (claims 9 & 11), a fourth protease composition including asclepain that is applied subsequent to the first wound healing stage (claims 13 & 15), and the claimed treating time (claims 1, 5, 9, and 13).
However, Kling does teach the method wherein said proteases include ficain, actinidain, and asclepain (para 0032), said proteases are useful for wound healing, reducing inflammation (an inflammatory stage) and promoting development of healthy skin (a proliferative stage / a remodeling stage) (para 0026), by varying the type and amount of proteases applied, the degree of protein degradation and consequently inhibition can be controlled (para 0024), one of skill in the art can choose an appropriate protease or combination of proteases to achieve the quality and quantity of modulation desired, the type and quantity of proteases used determines the level of inhibitory and/or activation modulatory effects on the target proteins, one of skill in the art can readily make modifications to the protease mixtures and observe the type and degree to which a given protein is inhibited (para 0025), lesser or greater levels of inhibition can be achieved by varying the type, content and amount of inhibitor polypeptides so that healing and healthy skin development is promoted, depending on the wound etiology, the patient immune system and the tissue trauma, various formulations could be developed in order to provide an optimal protein and enzyme activation and inactivation ratios specific for the disease (para 0038), and the dosage and method of administration can vary depending upon the location of the skin or tissue to be treated and/or upon severity of the wound (para 0040). In addition, Schultz teaches at each of the physiological stages of normal wound healing, controlled proteases are necessary for wound healing, these proteases must always be present in the right places, at the right times and at the right levels (p.2 col left – para 2). Schultz teaches elevated levels of active proteases and excessive protease activity greatly reduce the probability of healing unless appropriate interventions are in place (p.2 col right – para 1, p.3 col right – last para). Finally, Schmalz teaches a typical inflammatory response last 48-72 hours (p.1 para 3).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply an appropriate protease during various wound healing stages and to treat an area of skin for a desired period of time depending upon the location of the skin or tissue to be treated and/or upon severity of the wound, since Kling discloses that claimed proteases are useful for wound healing, reducing inflammation (an inflammatory stage) and promoting development of healthy skin (a proliferative stage / a remodeling stage), that one of skill in the art can choose an appropriate protease or combination of proteases to achieve the quality and quantity of modulation desired depending upon the location of the skin or tissue to be treated and/or upon severity of the wound, that various formulations could be developed in order to provide an optimal protein and enzyme activation and inactivation ratios specific for the disease, Schultz discloses that elevated levels of active proteases and excessive protease activity greatly reduce the probability of healing, that proteases must always be present in the right places, at the right times and at the right levels, and Schmalz discloses that a typical inflammatory response last 48-72 hours. In other words, one of skill in the art would apply specific proteases during various wound healing stages for an optimal period of time to target different proteins depending on the disease conditions and to better control the level of protease activity to promote tissue repair and wound healing. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references to apply an appropriate protease during various wound healing stages and to treat an area of skin for a desired period of time, with a reasonable expectation of success.
References cited above do not teach the claimed concentration (claims 4, 8, 12, and 16).
However, Kling does teach the method wherein the proteases can be formulated into a therapeutic composition including a solution (para 0039), the proteases form about 1.0% to about 10% by weight of the composition, the amount of the proteases required for healthy skin development or wound treatment will vary not only with the route of administration, but also the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician (para 0040).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to optimize the concentration of proteases in a solution, since Kling discloses that proteases form about 1.0% to about 10% by weight of the composition, and that the dosage vary depending upon the location of the skin or tissue to be treated and/or upon severity of the wound. Generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. (MPEP 2144.05 II) Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate an optimized concentration of proteases to a skin area with a reasonable expectation for successfully modulating the protein profile of a tissue or its surrounding environment to promote the repair of a damaged tissue, or one that is otherwise compromised by disease or injury.
Response to Arguments
Applicant argues that cited references do not teach or suggest the specifically claimed multi-stage treatment protocol wherein different protease compositions are applied during distinct wound healing stages selected from hemostasis, inflammatory, proliferative, and remodeling stages as amended in the claims. However, these arguments are moot since those rejections are withdrawn in view of applicant’s amendments.
Applicant argues that the specification at paragraph [0094] discloses concentrations of approximately 10-8 to 2% (w/v), and paragraphs [0095]-[0096] provide specific sub-ranges (e.g., 0.001 µg/ml to 0.01 µg/ml), confirming that the lower end of the claimed range is a purposeful feature of the invention, not merely a routine optimization.
These arguments are not found persuasive because differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. (MPEP 2144.05 II) In the instant case, applicant has failed to demonstrate the criticality of the claimed concentration.
Conclusion
No claims are allowed.
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 extension fee 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759
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