DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed September 22, 2025. Currently, claims 1-7, 13, 64-75 are pending. Claims 65-75 have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
This action is FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election of Group I, baldness, male pattern baldness, Androgen receptor and RS6152 in the paper filed June 13, 2024 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 65-75 have been withdrawn as non-elected subject matter.
Priority
This application claims priority to
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Information Disclosure Statement
It is noted that the IDS filed January 27, 2025 and June 10, 2025 contains an extremely large number of references for consideration by the Examiner. The January 27, 2025 IDS is 42 pages and the June 10, 2025 IDS is 26 pages. If the Applicant and/or Applicant and/or Applicant's representative are aware of any particular reference or portion of a reference in the extensive list which the examiner should pay particular attention to, it is required that it be specifically pointed out in response to this Office action.
Applicant is reminded that "burying" relevant references in a lengthy IDS is discouraged. See, e.g., Molins PLC v. Textron Inc., 48 F.3d 1172, 33USPQ2d 1823, 1831 (Fed. Cir. 1995) The court concluded that, by “burying” Wagenseil in a multitude of other references, Hirsh and Smith intentionally withheld it from the PTO becausethis manner of disclosure was tantamount to a failure to disclose. Citing Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F.Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), aff'd, 479 F.2d 1328, 178 USPQ 577 (5th Cir.), cert. denied, 414 U.S. 874 (1973), the court stated that Hirsh's and Smith's failure to highlight Wagenseil in light of their knowledge of Whitson's actions in the foreign prosecutions violated their duty of candor to the PTO. Citing our precedent, Textron asserts that Smith's and Hirsh's conduct is “inexcusable,fraudulent, and cannot operate to cure Whitson's inequitable conduct.” See
Rohm & Haas Co. v. Crystal Chem. Co., 722 F.2d 1556, 220 USPQ 289 (Fed.Cir. 1983), cert. denied, 469 U.S. 851 (1984) (where intentional material misrepresentations have been made, a “cure” through voluntary efforts during prosecution must be demonstrated y clear, unequivocal, and convincing evidence).
Response to Arguments
The response provides 14 references identified in a search of the IDS for particular review.
Specification
The specification has been amended to remove the reference to Figures.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation 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.
Claims 1-7, 13, 64 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 claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims
Claims 6-7 are directed to a treating baldness using the MSC exosome composition. Claims 1-5, 13, 64 have been amended to recite the intended use of the composition for treatment.
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The unpredictability of the art and the state of the prior art
Yuan et al. (E. J. of Pharmacology, Vol. 881, August 15, 2020) published after the filing date of the application reviews current advances in stem cell-based therapies for hair regeneration. Figure 1 illustrates currently available treatments for hair loss which does not include exosomes. Yuan reviews exosomes and their use for hair treatment (para 4). Yuan clearly states “there are no clinical studies regarding the use of exosomes or EVs for the treatment of hair loss” (para 5). Table 4 further provides the limitations of exosome for hair regeneration.
Istanbul Med Assist further considers whether exosomes work for hair loss (IMA, 2024, https://www.istanbulmedassist.com/blog/do-exosomes-really-work-for-hair-loss/#:~:text=Do%20Exosomes%20Actually%20Work?,%2C%20age%2C%20and%20overall%20health.). IMA states that in 2024 research is currently being done to determine whether exosome treatment works for hair loss but experts warn that more extensive, long-term research is necessary to properly prove its usefulness, the majority of the evidence is anecdotal.
Guidance in the Specification.
The specification provides no evidence that an MSC exosome composition comprising the rs6152 SNP may treat baldness. The specification is filled with definitions and prophetic discussions. There is no evidence of any MSC exosome comprising rs6152 treats baldness.
The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention.
Working Examples
The specification has no working examples of treating baldness with the MSC exosomes.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to treat baldness using an exosome created from a MSC lacking the rs6152 SNP. The specification fails to treat baldness using the MSC exosome composition. The art teaches exosomes to treat hair loss is being researched but extensive unpredictable experimentation is required before exosomes may be used to treat hair loss. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of a working example and the negative teachings in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
The response traverses the rejection. The response asserts a patent need not teach and preferably omits what is well known in the art. This argument has been considered but is not deemed persuasive. The prior art does not teach a method for creating MSC exosome compositions for treatment of baldness. In fact, the art demonstrates exosomes to treat hair loss is being researched but extensive unpredictable experimentation is required before exosomes may be used to treat hair loss.
The response asserts the claim is fully enabled by the specification at paragraphs 54, 97-99, 119-122. Paragraphs 97-99 do not provide any evidence or discussion of what was administered or the results, for example. Paragraphs 119-122 are directed to reducing oxygen levels to hypoxic conditions and wound healing. The specification does not provide any guidance to how reducing oxygen levels treats baldness. There is no nexus between the passage in the specification and the claims. There is no evidence in the specification to overcome the evidence in the art. The art teaches exosomes to treat hair loss is being researched but extensive unpredictable experimentation is required before exosomes may be used to treat hair loss.
The response asserts and the examiner agrees the art enables how to identify a SNP of Rs6152 in a patient that is not associated with disease. The enablement argument does not suggest that this aspect of the claimed invention is not enabled. Instead formulating and treating MSCs into a treatment is unpredictable. The response merely states that working examples for treating baldness is not required. The response also points to Sasaki et al. (Aesthetic surgery journal, Open Forum 4: ojac045, 1-15 (2022)). It is noted Sasaki is published nearly 2 years post-filing date and does not demonstrate the state of the art at the time the invention was made. Sasaki states that “no evidence-based data has been published” (page 3, para 1). Even more the Sasaki paper does not provide the method for bone marrow MSCs culturing or formulating or the presence of a SNP in the exosomes such that the results have any bearing on the instant claims. XoFLo is a bone marrow mesenchymal stem cell-derived EV isolate, but there is no evidence these exosomes have SNP difference associated with baldness. Sasaki does not mention SNPs.
Thus, for the reasons above and those already of record, the rejection is maintained.
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.
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 1-5, 13, 64 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Brenner et al. (US 2013/0129688, May 2013) in view of Kordelas et al. (Leukemia, pages 935-979, 2014) and Hayes et al. (Cancer Epidemiol Biomarkers Prev, Vol. 14, No. 4, pages 993-996, 2005) and further in view of Brodie et al. (US 2019/0269739, September 5, 2019).
Brenner teaches methods of selecting mesenchymal stem cells for therapeutic effectiveness by determining a variant. Brenner teaches analyzing a sample for an allele and selecting donors having a therapeutic allele, obtaining a population of MSCs from a donor (see para 10, 28, for example). Brenner thus teaches obtaining MSCs from donors that lack the mutant SNP that causes disease.
Brenner does not teach culturing the MSCs to prepare an exosome preparation.
However, Hayes teaches the AR-E211 G>A (rs6152) SNP “A” allele is associated with a lower risk of vertex and vertex-frontal baldness. Hayes further teaches the “A” allele does not appear to have a significant effect on frontal baldness.
Kordelas teaches MSC-derived exosomes as a novel tool to treat therapy-refractory graft-versus-host disease. Kordelas teaches MSC exosomes are ideal therapeutically active component of MSCs and the application of exosomes provides a number of advantages compared to the MSC application itself. Kordelas teaches the regulatory items to produce exosome fractions for clinical treatment strategies should be less complicated than for any cellular therapeutic of in vitro expanded cells (page 971, col. 1). Further, it might be possible to harvest exosomes from supernatant of immortalized MSC cell lines which could not be used for cellular therapies. Kordelas then teaches raising MSCs from 4 (four) different unrelated bone marrow donors (see page 971, col. 1). Kordelas teaches a method of culturing and enriching fractions that contain proportions of exosomes (page 971, col. 2).
Further, Brodie teaches mesenchymal stem cell populations may cultured to obtain exosomes (para 219). Brodie teaches growing MSCs in hypoxic conditions (i.e. low oxygen) or incubated in medium with low pH increases the yield of exosomes (para 219). Brodie teaches hypoxic conditions is below 5% oxygen (see para 243). Brodie also teaches low pH is at or below 6.0 (i.e. about 6.0)(see par 249).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have modified the MSC treatment method of Brenner to have prepared an MSC exosome preparation for baldness by screening for rs6152 “A” allele associated with baldness, as taught by Hayes and Kordelas, using 0.1%-10% oxygen and pH of 6.0, as taught by Brodie to generate mesenchymal stem cell exosome compositions for treatment of diseases. Kordelas teaches culturing and raising MSC exosomes for treatment of disease. Brodie teaches conditions to improve exosome yield. The ordinary artisan would have been motivated to have improved exosome yield to produce more exosomes for therapy, as suggested by Kordelas.
With respect to Claim 2, Kordelas teaches analyzing the MSC exosome-enriched fractions for growth factor beta and HLA-G (page 972, col. 1).
With respect to Claim 3, the growth factors were identified by western blot analysis (i.e. proteomic analysis).
With respect to Claims 4-5, Brodie teaches analyzing RNAs following culturing.
Response to Arguments
The response traverses the rejection.
The response argues Hayes is entirely silent as to the detection of the presence or absence of a SNP in the generation of an MSC-derived exosome for composition for the treatment of baldness, it cannot be considered analogous art. This argument has been reviewed but deemed not persuasive. Brenner teaches methods of selecting mesenchymal stem cells for therapeutic effectiveness by determining a variant. Brenner teaches analyzing a sample for an allele and selecting donors having a therapeutic allele, obtaining a population of MSCs from a donor (see para 10, 28, for example). Brenner thus teaches obtaining MSCs from donors that lack the mutant SNP that causes disease. Hayes teaches the SNP associated with baldeness. The ordinary artisan would have been motivated to have designed a MSC from a donor without the SNP for baldness to treat baldness. The SNP reference of Hayes is the same field of endeavor for biotechnology genotyping for the purpose of treating a disease. Identifying SNPs associated with disease and disorders would have found Hayes reasonably pertinent to the problem of treating baldness.
The response asserts Kordelas does not teach or disclose the culturing conditions or genotyping a targeted donor for absence of SNP associated with baldness. This argument has been reviewed but is not persuasive. Brodie teaches the culturing conditions and Brenner teaches the genotyping step. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The response argues Brenner does not teach culturing MSCs to prepare exosome preparation. This argument has been considered but is not convincing because these limitations are taught by Brodie. The response asserts there is no motivation to combine the references but provides no arguments. As noted in the rejection above, it would have been obvious to have modified the MSC treatment method of Brenner to have prepared an MSC exosome preparation, as taught by Kordelas, using 0.1%-10% oxygen and pH of 6.0, as taught by Brodie to generate mesenchymal stem cell exosome compositions for treatment of diseases. Kordelas teaches culturing and raising MSC exosomes for treatment of disease. Brodie teaches conditions to improve exosome yield. The ordinary artisan would have been motivated to have improved exosome yield to produce more exosomes for therapy, as suggested by Kordelas. Thus, for the reasons above and those already of record, the rejection is maintained.
The response argues that the combination of references fail to provide a person of skill in the art a reasonable expectation of success. It is noted that the case provides both an enablement rejection and an obviousness rejection. It is noted that if the specification is enabling, then so are the references, and the claims may be unpatentable over the teachings of this references. If the references are not enabling, neither is the specification, which would also make the claims unpatentable. The examiner is not able to choose based on the limited evidence provided which is the more correct rejection, however either rejection would render the claims unpatentable. Therefore, the examiner has made a superficially inconsistent art and enablement rejection and places the burden on the Applicants to distinguish his or her specification from the prior art and to point out how the specification goes beyond and elaborates upon what is taught by the previously published reference. In the instant case the specification and the scope of the claims clearly imply that it is possible to treat baldness using MSC exosomes with SNP profiles not associated with baldness. If this is true then the claims are rendered obvious in view of the combination of references cited in the 103 rejection. Applicant argues there is no undue experimentation and a reasonable expectation of success in the enablement rejection above and yet argues there is no reasonable expectation of success in the 103. The response is taking positions in opposite of one another.
The response argues unexpected finding that specific MSC populations are amendable to treatment specific diseases and disorders. This argument has been reviewed but is not persuasive. Applicant is requested to point to the unexpected results in the specification and the specific MSC populations with these unexpected properties. The instant claims are not commensurate in scope with any particular MSC populations that treat baldness. A showing of specific MSC populations that treat and inhibit glioblastoma is not commensurate in scope with the claims.
Sasaki et al. (Aesthetic surgery journal, Open Forum 4: ojac045, 1-15 (2022)) is published nearly 2 years post-filing date and does not demonstrate the state of the art at the time the invention was made. Even more the Sasaki paper does not provide the method for bone marrow MSCs culturing or formulating or the presence of a rs6152 SNP in the exosomes such that the results have any bearing on the instant claims.
Conclusion
No claims allowable.
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 JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
October 19, 2025