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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 39-58 were previously 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 was previously acknowledged.
Receipt is acknowledged of the amendments to the claims submitted on 03 August 2026. Claims 39-54, 56, and 58 are amended.
Claims 53-58 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The Examiner thanks Applicant for properly labelling claims 53-58 as withdrawn in the response submitted on 03 August 2026.
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 statement (IDS) submitted on 03 August 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered 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.
Withdrawn Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Objections
The objections to claims 39, 44-45, and 47-48 are withdrawn in view of Applicant’s amendments to the claims. Applicant has corrected the issues that were previously objected to.
Claim Rejections - 35 USC § 101
The rejection of claims 50-52 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended claims 50-52 to recite a method with affirmative steps rather than a mere use with nothing more.
Claim Rejections - 35 USC § 112 (a) Written description
In view of Applicants’ amendment of the claims, the rejection of claims 39-52 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 has been withdrawn.
Claim Rejections - 35 USC § 102
The rejection of claims 39-40, 43-44, and 50-51 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”) is withdrawn in view of Applicant’s amendments to the claims. Gilleard does not teach a number of cells per dose.
Maintained Rejections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
Claims 40, 42-48, and 50-52 remain rejected and claims 39, 41, and 49 are newly 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.
Applicant amended the claims to correct the previously raised issues of indefiniteness but the amendments introduced new issues of indefiniteness in themselves. Therefore, this rejection is maintained and newly applied to claims previously not rejected under 35 U.S.C. 112(b) but which are now indefinite.
Claim 39 recites the limitation "the freshly isolated cell preparation" in sixth line of the claim and “the cells” in the eighth line of the claim. There is insufficient antecedent basis for these limitations in the claim. Nowhere in claim 39 is there a recitation of a freshly isolated cell preparation. In addition, the claim recites “cells comprising primary dermal fibroblasts” and “freshly isolated cells” which appear to be two distinct antecedents to which “the cells” could be referring. It is unclear which antecedent is intended here. Claims 40-49 are further rejected for their dependency on a rejected base claim.
Claims 40, and 44 similarly recite “the cells” multiple times while depending from claim 39. Therefore, claims 40 and 44 are also rejected for lack of antecedent basis as claim 39 itself s unclear with regard to which cells are “the cells”.
Claim 50 recites the limitation "the cells" in the sixth line of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 50 is an independent claim which recites “an autologous freshly-isolated cell preparation” but not “cells”. This in itself would not be ambiguous but for the reference to “the autologous freshly-isolated cell preparation” separately in the claim. With this recitation, it appears that the use of the term “the cells” was deliberate and was intended to refer to something distinct from the cell preparation yet no antecedent was provided for “the cells”. Accordingly, the metes and bounds of claim 50 cannot be determined and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Claims 51-52 are further rejected for their dependency on a rejected base claim.
Claims 39-52 remain 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 any administration to an area of skin of 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.
This rejection has been modified as necessitated by Applicant’s amendments to the claims. While Applicant has amended the claims to comply in part with the enabled claim scope previously identified, the claims continue to read on a vast genus of administration methods while the art evidences only several and the specification itself evidences none.
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 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 wherein the fibroblasts are administered via any route to the subject (for example: orally, topically, central catheter). It is noted that administering to an area of skin of a subject still reads on administering to that area of skin by all of the listed ways above. This breadth 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. Further, 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 administration other than intradermal injection might be used. 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, fibrin glue applications, or spray on applications (Thangapazham, “3.3.” subheading). In each of these cases, the cells are applied topically and directly to the site being treated (Thangapazham, “3.3.” subheading). The cells are typically injected into the site being treated in the art at the time of filing (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. Thus, the art at the time of filing evidences unpredictability in the administration via any means because the art at the time of filing lacks teachings of methods of administration other than those of applying the cells directly to the site being treated via injection or topical application.
As well, the claims are drawn to a large genus of administration modes. 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).
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 of filing would have had no basis to reasonably predict or conclude the claimed methods of 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 physiological activity. 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 lack of any working example of a treatment, the lack of guidance in the specification for 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.
Response to Arguments
Applicant argues that the amended claims comply with the enabled claim scope identified by the office (Remarks, pages 9-10), and that the amended claims satisfy the written description requirement (Remarks, page 11). These arguments have been fully considered but have not been found persuasive.
First, it is acknowledged that even a considerable amount of experimentation is not undue (as pointed out by Applicant). However, the amended claims still read on any route of administration insofar as they do not require application of the cells directly to the affected site. For example, one would still fall within the scope of the claim were they to orally administer fibroblasts to a human with the goal of some of those fibroblasts getting to the affected skin. In addition, the claim does not require the direct administration of the specified dose of cells to the affected skin by this same logic so long as 10,000 cells are “administered” even if only 1 makes it to the affected skin. This issue is presented still in both of the independent claims and the rejection above sets forth precisely why this presents an issue under both enablement and written description. Applicant has not engaged with the art at the time of filing to argue in favor of the vast genera they have claimed, nor have they even attempted to engage with the art cited by the office in determining the enabled claim scope. While example 3 in the instant application shows an in vitro culture example of application of fibroblasts, this does not show that Applicant themselves actually carried out a treatment of any of the claimed skin disorders via any route of administration at all. This is precisely why the art at the time of filing is so relevant to the determination of compliance with 35 U.S.C. 112(a) in the present case. Accordingly, the arguments have been fully considered but have not been found persuasive.
Claim Rejections - 35 USC § 102
Claims 39, 41-45, 47-50, and 52 remain 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”). This rejection has been modified as necessitated by Applicant’s amendments to the claims.
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). 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 more than 50% representation of fibroblasts in the cell population claimed. Further, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph). Thus, Watt discloses the method of claim 39.
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 a cosmetic method (Watt, page 18, third paragraph).
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). 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 more than 50% representation of fibroblasts in the cell population claimed. Further, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph).
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.
Response to Arguments
Applicant argues that Watt does not disclose the invention claimed in a single embodiment but rather discloses ex vivo expansion and direct administration as alternative embodiments and that Watt teaches that ex vivo expansion is desirable for therapeutic applications (Remarks, page 13). This argument has been fully considered but has not been found persuasive.
Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); < Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Here, just because Watt teaches a “desirable” embodiment does not detract from the weight of other embodiments taught elsewhere in the reference. Even assuming arguendo that it did counter novelty in some way, the claims read on cosmetic methods which Watt explicitly indicates for leaving out the ex vivo expansion step. In addition, it is not as if Watt’s teaching disparate methods with no connection. Watt teaches therapeutic methods which encompass the invention claimed and specifically teaches that those methods can be without an ex vivo expansion step which is particularly desirable where the method is a cosmetic method. Accordingly, this argument has been fully considered but has not been found persuasive.
Claim Rejections - 35 USC § 103
Claims 39 and 46 remain 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”. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
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). 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 more than 50% representation of fibroblasts in the cell population claimed. Further, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph). 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.
Response to Arguments
Applicant argues that the combined prior art references do not teach all of the limitations now claimed (Remarks, page 15), that Watt teaches away from the instant invention by teaching that ex vivo expansion is desirable for therapeutic applications (Remarks, page 15), and that the application presents unexpected results (Remarks, page 15). These arguments have been fully considered but have not been found persuasive.
First, the combined prior art references do teach all of the limitations now claimed. The amendments introduced limitations found elsewhere in the claims and introduced a property of the cell population that the population of Watt is presumed to possess considering the fact that the instant cells and the cells of Watt were produced through identical methods. Second, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Here, Watt’s teaching of the desirability of ex vivo expansion in therapeutic applications does not constitute a teaching away because Watt also specifically teaches that the method can exclude an ex vivo expansion step. Still further, the claimed methods read on a cosmetic method which Watt specifically suggests as the context for dropping ex vivo expansion. Third, evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). See also MPEP 716.02e. In this case, Applicant is arguing unexpected results for elements of the invention that were anticipated by Watt. Applicant has not attempted, for example, to argue that their use of collagenase (the limitation rendered obvious via the combination of references) produced unexpected results. Further, Applicant has not attempted to conduct a direct or indirect comparison of their method with the method of Watt to argue that their results are anything other than what would be expected were a person having ordinary skill in the art to follow the Watt reference. On the whole, this third argument appears to be an attempt to distinguish the present invention from that in Watt on grounds only applicable to rebutting a prima facie case of obviousness and not applicable to the novelty analysis under 35 U.S.C. 102. The obviousness rejection rests on the combination of Watt, Miltenyi, and Wang and the argument for unexpected results here focuses only on the method of Watt without comparing the instant invention to the method of Watt directly or indirectly to provide a basis for finding an unexpected result. It is noted that Applicant’s argument here also rests on the assertion that the art “taught toward cultured cells and larger cell numbers” (Remarks, page 16). The art (Watt) taught to exclude ex vivo expansion and taught to use a dose as low as the instant invention. Accordingly, these arguments have been fully considered but have not been found persuasive.
New Rejections Necessitated by Applicant’s Amendments to the Claims
Claim Rejections - 35 USC § 103
Claims 39-40, and 50-51 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019/122931 (published: 27 June, 2019) (Hereinafter “Watt”) in view of Thangapazham, et al. International journal of molecular sciences 15.5 (2014): 8407-8427, hereinafter “Thangapazham”.
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). 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 more than 50% representation of fibroblasts in the cell population claimed. Further, Watt discloses a single dose may comprise 10,000 cells (Watt, page 20, first paragraph). Thus, Watt discloses the methods of claims 39 and 50.
Watt does not explicitly teach to administer the cells within 48 hours of isolating them.
However, a person having ordinary skill in the art at the time of filing knew that avoidance of the loss of unique cellular identity of autologous fibroblasts used in therapies is an important consideration and that one of the main disadvantages of expansion steps is that they are time consuming (Thangapazham, “3.2.” subheading). While the method of Watt does not explicitly teach to administer the cells within 48 hours of isolation, a person having ordinary skill in the art would have known that they could have done so because the cells would be ready for application following isolation in a method without an expansion step. The results of doing so would have been predictable insofar as the cells of Watt would have predictably functioned immediately after isolation better than they would have with waiting a length of time in consideration of the teachings of Thagapazham. Even further, a person having ordinary skill in the art would have been motivated to immediately administer the cells following isolation to better preserve their unique cellular identity as Thangapazham teaches this to be a priority in autologous fibroblast therapies.
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 immediately administered the fibroblasts of Watt following isolation and to have arrived at the invention claimed in instant claims 40 and 51 at least because they could have done so to produce predictable results but also because they would have been motivated to do so to better preserve their unique cellular identity as Thangapazham teaches this to be a priority in autologous fibroblast therapies. There would have been a reasonable expectation of success in doing so because following isolation, the cells themselves are ready for use when the method does not include an expansion step.
Conclusion
No claim is 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 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.
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.
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, MARIA G LEAVITT can be reached at 571-272-1085. 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.
/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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