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 .
Applicant’s election without traverse of Group I, claims 1-3, 15 and 16, in the reply filed on 27 April 2026 is acknowledged.
Claims 14, 17 and 18 have been cancelled.
Claims 4-11 have been withdrawn as being directed to a nonelected invention.
Claims 1-3, 12, 13 and 15-16 are presented for examination on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 12, 13 and 15-16 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 1 is rendered vague and indefinite by the phrase “an improved adipose-derived stem cell conditioned medium (ASC-CM) or secretome”. The term “improved” is a relative term which renders the claim indefinite. The term “improved” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. That is – what is the ASC-CM compared to in order to determine an improvement? Improved in what characteristic? Efficacy in treating ALS?
Appropriate clarification is required.
Claim 12 is indefinite because it is unclear where the itemized steps are to be placed within the method of independent claim 1. That is – the method of claim 1 includes the steps of “isolating, growing and stimulating”, but it is unclear if the recited steps of claim 12 are additional steps to these or further define “isolating, growing and stimulating”. Perhaps, it would help to clarify the claimed method to itemize the steps of claim 1 as done in claim 12, which would allow easier reference in the dependent claim(s).
Appropriate clarification is required.
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under U.S.C. 112, second paragraph, for the reasons set forth above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 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.
Claim(s) 1-3, 12, 13 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Trzyna et al. (2021) in view of Bunnell et al. (2008) and Roxburgh et al. (2016) and Estes et al. (2010) [cited by Applicant in IDS filed 2/3/26] in view of Wahyungingsih et al. (2020).
Trzyna et al. discloses a method of obtaining an improved adipose-derived stem cell conditioned medium (ASC-CM) (ASC-conditioned medium, page 6 second paragraph) or secretome with a profile of secreted factors capable of use in the treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders and in different embodiments, Tryzna discloses isolating (ASCs isolated from WAT, page 10 third paragraph), growing and stimulating adipose-derived stem cell in a growth media containing one or more growth factors (ASCs stimulation with FGF-2 or epidermal growth factor (EGF), page 5 third paragraph). The previous disclosure of Tryzna includes isolating (ASCs isolated from WAT, page 10 third paragraph), growing and stimulating adipose-derived stem cell in a growth media containing one or more growth factors (ASCs stimulation with FGF-2 or epidermal growth factor (EGF), page 5 third paragraph), and provides the benefit of increasing the secretion of desirable factors including HGF (Tryzna reference; page 5 third paragraph). Trzyna further discloses wherein the growth factors are selected from one or more of: HGF, PDGF-AA, EGF (ASCs stimulation with FGF-2 or epidermal growth factor (EGF), page 5 third paragraph), HB-EGF, GDNF, NT-4, bFGF, VEGF-A, TGF-B3, SCF, TGF-B2, VEGF-D, IGF-IR, M-CSF, IGF-2, NT-3, PDGF-AB, IGF-1, PLGF, bNGF, PDGF-BB, TGF-a, and GCSF.
Trzyna further discloses wherein the growth media containing one or more cytokines selected from: Pentraxin-3, PAI-1, Thromnospondin-1, MCP-1, IL-8 (adipose-derived stem cells secrete other cytokines with a well-defined pro-inflammatory properties such as IL-7, IL-8, page 5 second paragraph), GROa/CXCLI, Dkk-1, Chitinase-3-like-l, MCP-3, IGFBP-3, HGF (HGF production is increase, page 5 third paragraph), ENA-78/CXCL5, uPAR, Osteopontin, Emmprin/CD147, MMP-9, MIC-I/GDF-15, VEGF, TFF3, IL-6 SDF-la, Endoglin/CD105, Adiponectin, IL-17A, SHGB, IFN-gamma, Andiopoietin-2, Angiogenin, GM-CSF, IL-la, Lipcalin-2, Vitamin D-BP, Kallikrein-3, CD40L, FGF-19 and CD30.
Trzyna discloses the method for obtaining an improved adipose-derived stem cell conditioned medium (ASC-CM) (ASC-conditioned medium, page 6 second paragraph) of claim 1, comprising: i) isolating subcutaneous adipose tissue samples were obtained from a patient, wherein the tissue sample is obtained from lipo-aspiration or liposuction (advantage of MSCs isolated from AT is that they can be easily obtained by liposuction from autologous subcutaneous adipose tissue, page 2 first paragraph).
Trzyna discloses wherein the adlpose-derived stem cell conditioned medium (ASC-CM) comprises one or more growth factors (ASCs are better in the bioactive factors secretion such as nerve growth factor (NGF), hepatocyte growth factor (HGF), page 4 second paragraph).
Trzyna also discloses EGF cells such as (EGF, FGF-2, and TGF alpha are essential wound healing factors, enhancing these processes and cell migration, page 5 third paragraph).
Bunnell discloses: digesting the adipose tissue samples in filtered collagenase (collagenase digests of adipose tissue, page 2 third paragraph) type I (Collagenase Type I, page 3 second paragraph); separating the adipose-derived stem cells from the adipose tissue adipocytes via centrifugation to obtain a first pellet containing the
adipose-derived stem cells (ASCs, is obtained by centrifuging the sample this step completes the separation of the stromal cells from the primary adipocytes, page 3 second paragraph), treating the adipose-derived stem cell pellet with a red blood cell lysis buffer (The pellet is then resuspended in 1 ml lysis buffer, page 3 second paragraph) and further centrifuging to obtain a second adipose-derived stem cell
pellet (centrifuged at 2000 rpm for. 5 min. The supernatant is aspirated, the cell pellet, page 3 second paragraph); and, resuspending the second adipose-derived stem cell pellet in a growth medium (cell pellet is resuspended in a maximum of 3 ml of stromal medium, page 3 second paragraph) to stimulate the adipose-derived stem cells (Scheme for processing of adipose tissue and isolation of adipose-derived
stem cells, figure 1).
Roxburgh discloses wherein the adipose-derived stem cells are stimulated with a growth media comprising DMEM/F12 (DMEM:F12, table 1) produce the adipose-derived stem cell conditioned medium (ASC-CM) (isolation and proliferation of Adipose-derived stem cells, page 966 first column third paragraph) or secretome. Roxburgh does not disclose 5% FBS; EGF (5ng/ml); hFGF-B (10 ng/ml); ascorbic acid (250 uM).
Estes discloses a solution of FBS and DMEM/F12 (80% (v/v) FBS, 10% (v/v) DMEM/F.12, and 10% (v/v) DMSO, page 11 first paragraph).
Wahyungingsih et al. disclose that supplementing DMEM with ascorbic acid increased the cell division and suppressed the aging processes indicated by normal spread cell in size compared to cell cultured in DMEM and FBS without ascorbic acid supplementation.
It would have been obvious to a person of ordinary skill in the art, at the time of the effective filing date of the Application to have prepared ASC-CM for treatment of ALS by growing the cells in growth medium containing DMEM-F12, FBS, EGF, FGF and ascorbic acid as all are known in the prior art as appropriate components of growth media for ASC-CM, which are thought to be effective in treatment of ALS.
Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40oC and 80oC and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100oC and an acid concentration of 10%); See also, Peterson, 315 F.3d at 1330, 65 USPQ 2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references where held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ 2d 1843 (Fed. Cir.), cert denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ 2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ 2d 1362 (Fed. Cir. 1997).
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
Applicant’s invention appears predicated on an unexpected result (i.e., “improved” ASC-CM), - an unpredictable phenomenon, highly dependent upon specific conditions and/or amounts of particular ingredients. With respect to such unexpected results, please note that in KSR, the Court also reaffirmed that evidence of unexpected results may overcome an examiner's prima facie case of obviousness. KSR, 550 U.S. at 416 ("The fact that the elements worked together in an unexpected and fruitful manner supported the conclusion that Adams' design was not obvious to those skilled in the art" - discussing United States v. Adams, 383 U.S. 39). However, "any superior property must be unexpected to be considered as evidence of non-obviousness." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). Thus, "[m]ere improvement in properties does not always suffice to show unexpected results ....[W]hen an applicant demonstrates substantially improved results.., and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary." In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). Moreover, in order to establish unexpected results for claimed invention, objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support. In re Greenfield, 571 F.2d 1185, 1189 (CCPA 1978). Please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)).
Thus, the claimed method is deemed merely a optimized version of growth medium commonly-employed to grow ASC-CM, which would have been well within the purview of the skilled practitioner as routine experimentation to alter the components of a growth media to maximize its efficacy in producing ASC-CM for ALS treatment.
Accordingly, the instant claims, in the range of growth condition where no unexpected results are observed (e.g., “improved” efficacy of ASC-CM produced with a specific growth medium, that is – evidence of the criticality of the recited component amounts in the growth medium), would have been obvious to one of ordinary skill having the above cited references before him/her.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL G FIEBIG whose telephone number is (571)270-5366. The examiner can normally be reached M-F 8-4.
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/RUSSELL G FIEBIG/Examiner, Art Unit 1655
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