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 .
Claim Status
Claims 39-58 are pending.
Applicant’s election without traverse of the invention of group I drawn to methods of preventing or treating a skin condition (claims 39-52) in the reply filed on 27 April, 2026 is acknowledged.
Claims 53-58 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. It is noted that Applicant has failed to properly label claims 53-58 as withdrawn in the response submitted on 27 April, 2026. Applicant should be aware that, upon election, whether with or without traverse, Applicant should properly label pending claims as withdrawn when they do not read on the elected invention. See 37 C.F.R. 1.142.
Therefore, claims 39-52 are pending and are the subject of the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2022/057831, filed 24 March, 2022, which claims priority to United Kingdom of Great Britan and Northern Ireland Application No. GB2104130.6, filed 24 March, 2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copies of papers required by 37 CFR 1.55 have been filed in this application on 22 September, 2023.
The earliest possible priority for the instant application is 24 March, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 13 December, 2024, and 31 July, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 22 September, 2023 are accepted by the Examiner.
Examiner’s Comment
Throughout the present Official Action, where reference is made to the instant specification, the Examiner will be citing to the publication of the instant Application (US2024/0024369) for ease of citation.
Claim Objections
Claim 39 is objected to because the recitation of “a freshly-isolated cells” is grammatically incorrect as the indefinite singular article “a” is used with a plural noun “cells”. Appropriate correction is requested.
Claim 44 is objected to because of the following informalities: The claim recites “one or more of the following” then recites “and/or” in the list. This is redundant and Applicant should instead list the steps as separated by “and” since “one or more of the following steps” achieves the same ends as “and/or”. Appropriate correction is required.
Claim 45 is objected to because of the following informalities: Markush groups should be recited in the alternative (with “or” for example). Applicant should replace “and/or” with “or”. Appropriate correction is required.
Claims 17 and 48 are objected to because of the following informalities: both claims recite “selected from”. A proper Markush group should recite the phrase “selected from the group consisting of”. Appropriate correction is required.
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 40, 42-48, and 50-52 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 42 recites “and/or” in the second and fourth lines of the claim. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include, for example, that the cells are administered to skin of the subject within 48 hours only , or, that cells are administered to skin of the subject within 48 hours and isolating the cells from the skin sample “or” would imply that the function types are in the alternative. Appropriate correction is required.
Claim 42 recites “and/or” in the second line of the claim. This renders the claim unclear because it is unclear whether Applicant intends the scope of claim 42 to encompass cosmetic methods and the listed skin conditions or either of these in the alternative. This issue is confounded by Applicant’s description of cosmetic methods as encompassing methods of treating the listed skin conditions in claim 42 (See Specification, [0112]). Thus, it is unclear how these can be claimed in the alternative at all. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 42.
Regarding claim 43, the phrase "preferably" 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 44 and 48 recite a plurality of “and/or” conjunctions. While this may be a convenient means for Applicant, such legalese renders the claims indefinite because the claimed protein cannot be simultaneously be each of the structurally different molecules recited in parts (a), (b) and (c). As such, claim 44 is considered indefinite because it is grammatically awkward and it is unclear which limitations are required to be combined rather than alternative.
Regarding claim 45, the phrase "preferably" 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).
Additionally, claim 45 recites the term “and/or” in line 4 which renders the claim indefinite for the reasons set forth in the paragraphs above.
Claim 46 recites “one of the two or more enzymes comprises or consists of a collagenase”. This language renders claim 46 unclear because it is unclear how a single enzyme might “comprise” a collagenase. A single enzyme either is or is not a collagenase and it is unclear how an enzyme might be a collagenase and, for example, a papain. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought in claim 46. This rejection can be overcome by amending the claim to instead recite “consists of” in place of “comprises or consists of”.
Regarding claim 47, the phrase "preferably" 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 47 and 48 are indefinite in the recitation of “the cell isolation step” . There is not proper antecedent bases in the claim or parent claim 39.
Regarding claim 48, the phrase "preferably" 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 50-52 are directed to the use of an autologous freshly-isolated cell preparation. Claim 50 provides for the use of an autologous freshly-isolated cell preparation, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claims 51 and 52 recites the term “and/or” in line 2 which renders the claim indefinite for the reasons set forth in the paragraphs above.
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 39-52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating skin ageing, wrinkling, scarring or atrophy in a human, the method comprising isolating cells comprising primary dermal fibroblasts from a skin sample obtained from the human to obtain freshly-isolated cells; and intradermally injecting the freshly-isolated cells into skin of the human,
does not reasonably provide enablement for a method of preventing, nor a method of treating any skin condition, nor a method of treating any subject, nor administration by any route to the subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim 39-52 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 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.
While the written description and enablement requirements are separate and generally separable requirements, the instant application fails to meet either requirement for essentially the same reasons, as set forth below.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of the Invention. The instant claims are drawn to a method of preventing or treating a skin condition in a subject by isolating primary dermal fibroblasts from the subject and administering those fibroblasts back to the subject.
2) Scope of the Invention. The claims broadly encompass methods of prevention (requiring the ability to predict therapeutic necessity), as well as methods of treating any skin condition (for example: melanoma, erythropoietic protoporphyria, Argyria) in any subject (for example: human, dog, fish, reptile, bird, amphibian), as well as methods wherein the fibroblasts are administered via any route to the subject (for example: orally, topically, central catheter). This breadth not only establishes a vast scope needing support in the instant specification and the art at the time of filing to preclude the imposition of undue experimentation on skilled artisans, but also establishes a vast genus of methods in which any subjects needing treatment for any skin condition may be predicted and, thus, prevented from having the skin condition. This genus encompasses, for example, a method of preventing frogs from contracting chytridiomycosis (a fungal infection of frog skin) by predicting which populations of frogs will contract the disease, then isolating fibroblasts from the frogs and feeding the fibroblasts back to the same frogs. The burden is on the Applicant for supporting this genus in a manner sufficient for skilled artisans to believe that Applicant had possession of the claimed invention.
3) Number of Working Examples and Guidance. The specification provides working examples for the isolation of freshly-isolated dermal fibroblasts from humans ([0134], Example 1, [0143], Example 3). The working examples also describe comparing the marker profiles of the fibroblasts with or without an ex vivo expansion step ([0140]-[0141], Example 2, [0147], Example 4). The working examples also teach different methods of digestion of human dermal tissue ([0150]-[0160]). Where the working examples attempt to teach a treatment, only two paragraphs are provided ([0148]-[0149]). The first teaches that the same subject that the cells are isolated from is to be the subject being treated and that the administration is to be via intradermal injection of 100 μL doses containing 100,000 cells per cm2 of atrophic scar tissue ([0148]). No details are given besides these. The second paragraph attempts to support any possible treatment that has previously been taught in the art by incorporating by reference all of the publications referenced in the remainer of the specification ([0149]). Thus, the only reasonable conclusion from the working examples is that no actual treatment was performed. Rather, Applicant’s appear to be attempting to incorporate a method of isolating a naturally occurring population of fibroblasts into a method of treatment without ever actually performing such a treatment. No example is taught in which any skin condition is prevented, any subjects other than humans are used, nor any administration other than intradermal injection. In addition, no working example is provided for a method of treatment at all. Thus, the extent to which undue experimentation may be imposed upon a skilled artisan is entirely weighed by an evaluation of the art at the time of filing.
4) State of the Art. The use of autologous fibroblasts to treat facial contour deformities like wrinkles and scars is not new (Weiss, et al. Dermatologic surgery 33.3 (2007): 263-268. Hereinafter Weiss). In fact, Weiss teaches a phase III clinical trial in humans wherein autologous dermal fibroblasts were injected in dermal filler applications to treat scarring and wrinkles which was published in 2007 (Weiss, Abstract). Methods using autologous dermal fibroblasts typically start with a skin biopsy, followed by enzymatic isolation, culture, expansion, and purification (Thangapazham, et al. International journal of molecular sciences 15.5 (2014): 8407-8427, hereinafter “Thangapazham”, page 8410, “3.2.” subheading). These also are typically aimed at treating humans with autologous human fibroblasts for wound healing or cosmetic indications like facial rhytides (Thangapazham, “Introduction” subheading; “3.1.” subheading). In addition, the mode of administration is most commonly via injection to the affected site (Thangapazham, “3.3.” subheading).
5) Unpredictability of the Art. The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability M.P.E.P. § 2164.03.
Where the art teaches anything other than injection of autologous dermal fibroblasts as a treatment, it teaches topical application in the form of matrix suspensions (Thangapazham, “3.3.” subheading). In addition, the cells are typically injected into the site being treated (Weiss, Abstract). No teaching in the art at the time of filing has been found to support an oral administration of autologous fibroblasts to treat anything. In addition, no art has been uncovered for the treatment of skin conditions of fish or of frogs where autologous fibroblasts are harvested from the fish or frog to be treated. While preventing cosmetic conditions of the skin that can be reasonably predicted is possible (like wrinkling associated with ageing), no art has been uncovered which teaches preventing unpredictable skin conditions (like melanoma) from developing by administering fibroblasts. In addition, the art at the time of filing is concerned with the treatment of human skin conditions in this way and any teaching of other organisms appears to be limited to model organisms for humans as an incident of developing the cell therapies (See Thangapazham, page 8410, first paragraph). In addition, autologous fibroblast cell therapy is not one of the recognized treatment options for humans suffering from erythropoietic protoporphyria (Minder, et al. Cellular and Molecular Biology 55.1 (2009): 84-97, hereinafter “Minder”, whole document). Thus, the art at the time of filing evidences unpredictability in the prevention of any skin condition, and the treatment of any skin condition in any subject comprising administration via any means because the art at the time of filing lacks teachings of methods of preventing unpredictable skin conditions and of methods of treating anything other than humans for human-specific skin conditions like wound healing, and wrinkles.
As well, the claims are drawn to incredibly large genera of administration modes, skin conditions, and subjects. The physiological art is recognized as unpredictable. (MPEP 2164.03.) In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. It is not a question of safety but one of predictability. The claims require administration by many routes that are not potentially able to deliver enough “freshly-isolated cells” to achieve the end results in humans (like oral administration). Further, the claims are drawn to a genus of skin conditions encompassing conditions in which autologous fibroblasts are not recognized as a treatment because the factors causing the disease do not implicate fibroblasts at all (See Minder, whole document).
This raises issues under description as well as enablement. The description component of the rejection is herein included as you cannot use what you have not described. Furthermore, the enablement of the instant invention has been assessed in light of the specification and the prior art available at the time of filing. "However, claims reading on significant numbers of inoperative embodiments would render claims non- enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298,302 (CCPA 1971). (see MPEP 2164.08(b). Specifically, the method of administration is more limited than by any as claimed as set forth above. As well, for delivery of fibroblasts to specific sites, delivery directly to those sites is needed.
In addition, the claims are drawn to a method of prevention. This requires predicting the subjects that would require treatment which would be highly unpredictable. In humans, skin conditions are usually established before therapy is offered (wounds and melanoma for example). The specification does not adequately teach how to effectively predict for whom prevention would be required. One establishes a large genus of target subjects for whom the method is intended, however, establishing whether a person or persons actually requires the treatment is a highly unpredictable art. Screening procedures for indications of those requiring inhibition of the onset of disease are unknown and highly prejudicial leading to conditions in which those who require the treatment cannot be distinguished from those who do not. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. In this case, applicants exacerbate the unpredictability of the art by reciting subjects to be targeted for whom the disease must be prevented.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention.
Consequently, the prior art when combined with the lack of any disclosed direct experimental test of Applicant's hypothesized treatments, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed methods of preventing or treating could be identified given the lack of details necessary to identify those meeting the necessary functions. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
In view of the breadth of the claims, the relative lack of guidance in the specification for preventing any skin condition, and the lack of guidance in the specification for treating any subject with any skin condition by any route of administration of fibroblasts, and the unpredictability evidenced in the art at the time of filing, it would require undue experimentation for a skilled artisan to use the invention claimed. Further, in an unpredictable art, the disclosure of limited examples utilizing only human fibroblasts, the teaching of only a specific route of administration, and the lack of a teaching of any treatment of any skin condition at all would represent to the skilled artisan that applicants were not in possession of claimed genus.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 50-52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because claims 50-52 are directed to a use of an autologous freshly-isolated cell preparation. The claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e. results in a claim which is not a proper process under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ678 (Bd.App.1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp.131, 149 USPQ 475 (D.D.C.1966).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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 39-45, and 47-52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2019/122931 (published: 27 June, 2019) (Hereinafter “Watt”) (cited on the IDS submitted 13 December, 2024) as evidenced by Miltenyi whole skin dissociation kit data sheet (accessed: 05 May, 2026) (hereinafter “Miltenyi”).
Watt discloses methods of treating skin disorders in humans comprising administering isolated dermal fibroblasts to the humans (Watt, page 18, last two paragraphs, claims 22-23). Watt discloses directly administering the fibroblasts without ex vivo expanding the isolated fibroblasts and with the isolated fibroblasts being isolated from the human to be treated (Watt, page 18, last two paragraphs, claims 22-23). Thus, Watt discloses the method of claims 39-40.
Regarding claim 41, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph). Thus, Watt discloses fewer than 500,000 cells are administered per cm2 of the skin of the subject.
Regarding claim 42, Watt discloses treating skin ageing, wrinkles, or scarring (Watt, page 19, second paragraph). In addition, skin ageing, wrinkles, and scarring are all examples of skin atrophy.
Regarding claim 43, Watt discloses a skin sample of 5mm diameter which is 0.2cm2 (20mm2 = πr2 where r is 2.5mm)(Watt, page 26, first paragraph).
Regarding claim 44, Watt discloses to remove the epidermis of the skin sample (Watt, page 26, first paragraph).
Regarding claim 45, Watt discloses enzymatically digesting the dermis of the skin sample with the Miltenyi whole skin dissociation kit (Watt, page 26, first paragraph). Thus, Watt necessarily discloses enzymatic digestion with two or more enzymes as evidenced by Miltenyi which teaches that the whole skin dissociation kit relies on at least three different enzymes (Miltenyi, “2.1” subheading).
Regarding claim 47, Watt discloses sorting fibroblasts into subpopulations based on the expression of CD31, CD45, CD90, and CD324 (Watt, page 17, whole page).
Regarding claim 48, Watt discloses sorting fibroblasts into subpopulations based on the expression of CD26, CD39, and CD36 (Watt, page 17, whole page).
Regarding claim 49, it is noted that where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01. The claimed isolated fibroblasts are produced by identical or substantially identical processes to those disclosed in Watt. Therefore, the isolated fibroblasts of Watt are deemed to inherently possess the claimed cell count.
Regarding claim 50, Watt discloses methods of treating skin disorders in humans comprising administering isolated dermal fibroblasts to the humans (Watt, page 18, last two paragraphs, claims 22-23). Watt discloses directly administering the fibroblasts without ex vivo expanding the isolated fibroblasts and with the isolated fibroblasts being isolated from the human to be treated (Watt, page 18, last two paragraphs, claims 22-23).
Regarding claim 51, Watt discloses directly administering the fibroblasts without ex vivo expanding the isolated fibroblasts and with the isolated fibroblasts being isolated from the human to be treated (Watt, page 18, last two paragraphs, claims 22-23).
Regarding claim 52, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph). Thus, Watt discloses fewer than 500,000 cells are administered to the skin of the subject.
Claims 39-40, 43-44, and 50-51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gilleard, et al. Archives of Plastic Surgery 40.05 (2013): 627-629, hereinafter “Gilleard”).
Gilleard discloses a method of treating wounds from ablative skin cancer surgery comprising isolating cells comprising dermal fibroblasts (excising skin from patients with wounds, digesting the skin with trypsin to produce a complete population of cells including fibroblasts), and administering the cells to the skin of the subject (spraying onto donor site flaps) (Gilleard, Abstract; pages 627-628, last and first paragraphs respectively). Thus, Gilleard discloses the invention of instant claims 39, and 50.
Regarding claims 40 and 51, the method of Gilleard does not include an ex vivo expansion step.
Regarding claim 43, the skin sample of Gilleard is 10 mm x 5 mm which is 0.5cm2 (Gilleard, page 627, last paragraph).
Regarding claim 44, the method of Gilleard comprises scraping of the epidermis and enzymatically digesting the skin samples (Gilleard, page 628, first paragraph).
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.
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.
Claims 39 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019/122931 (published: 27 June, 2019) (Hereinafter “Watt”) in view of Miltenyi whole skin dissociation kit data sheet (accessed: 05 May, 2026) (hereinafter “Miltenyi”), and Wang, et al. In Vitro Cellular & Developmental Biology-Animal 40.8 (2004): 268-277, hereinafter “Wang”.
Watt discloses methods of treating skin disorders in humans comprising administering isolated dermal fibroblasts to the humans (Watt, page 18, last two paragraphs, claims 22-23). Watt discloses directly administering the fibroblasts without ex vivo expanding the isolated fibroblasts and with the isolated fibroblasts being isolated from the human to be treated (Watt, page 18, last two paragraphs, claims 22-23). Watt discloses enzymatically digesting the dermis of the skin sample with the Miltenyi whole skin dissociation kit (Watt, page 26, first paragraph). Thus, Watt necessarily discloses enzymatic digestion with two or more enzymes as evidenced by Miltenyi which teaches that the whole skin dissociation kit relies on at least three different enzymes (Miltenyi, “2.1” subheading). The precise types of enzymes in the Miltenyi kit are proprietary.
Thus, Watt does not specifically teach to use collagenase in the enzymatic digestion step.
However, Watt does teach that collagenase can be used to isolate fibroblasts from skin (Watt, page 25, last paragraph). In addition, Wang teaches to use Clostridium histolyticum collagenase (CHC), teaches that CHC contains collagenase, neutral protease, clostripain, and trypsin, and teaches that the efficient digestion of human dermal skin in CHC requires a mixture of collagenase, neutral protease, and clostripain activities (Wang, Summary; page 275, fifth paragraph). Wang also teaches that CHC is most frequently used for isolation of dermal fibroblasts (Wang, page 269, first paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have digested the dermal tissue of Watt with two or more enzymes wherein one of those enzymes consists of collagenase as taught by Wang and to have arrived at the invention claimed in instant claim 46 with a reasonable expectation of success because they would have been motivated to do so leverage a frequently used enzymatic mixture comprising collagenase to efficiently isolate dermal fibroblasts. There would have been a reasonable expectation of success in doing to insofar as Wang teaches that CHC is frequently used to isolate dermal fibroblasts.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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