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 .
Response to Amendments
Applicant's amendments filed 7/31/2026 to claim 1 have been entered. Claims 2, 9, and 11 are canceled. Claims 1, 3-8, and 10 remain pending, of which claims 1 and 3-7 are being considered on their merits. Claims 8 and 10 remain withdrawn from consideration. References not included with this Office action can be found in a prior action. The 35 U.S.C. § 102 rejections of record over Murphy are withdrawn in view of the instant amendments to claim 1.
Any other rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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 1 and 3-7 are is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 1 is directed towards a method, and recites wherein the cells are seeded into the culture dish in an initial required number of single cells calculated by the claimed equation. Therefore, the claim is directed towards a mathematical formula and calculations and so necessarily is directed towards an abstract idea. See M.P.E.P. § 2106.04(a)(2).
This judicial exception is not integrated into a practical application because the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception itself. Regarding the other elements of claim 1 and claims 3-7, seeding known quantities of mesenchymal stem cells (MSCs) to generate MSC spheroids of known radii (and so diameter) is routine and conventional in this art over Murphy et al. (J. R. Soc. Interface (2016), 14: 20160851). Murphy teaches a method producing a mesenchymal stem cell (MSCs) spheroid, the method comprising 1) measuring the diameter of the MSCs by estimating the MSC diameter to be about 15 µm (subheading 2.5), 2) seeding 15000 (i.e. 1.5 * 104), 30000 (i.e. 3 x 105), or 60000 (i.e. 6 x 105) MSCs into a hanging drop culture dish and obtaining an MSC spheroid by culturing the MSCs in 25 µl hanging drops for 48 hours (i.e. 2 days) (subheading 2.2), and 3) obtaining MSC spheroids with radii of 176 ± 8 µm, 251 ± 12 µm and 353 ± 18 µm, respectively for the initial 15000, 30000 and 60000 cells per spheroid (Abstract), and which equates to diameters of 88 ± 4 µm, 125.5 ± 6 µm and 176.5 ± 9 µm (i.e. diameter = 2 * radius).
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 1 and 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (J. R. Soc. Interface (2016), 14: 20160851).
Other species were found during the search. This rejection addresses the embodiment of bone marrow-derived mesenchymal stem cells.
Murphy teaches a method producing a bone marrow-derived mesenchymal stem cell (MSCs) spheroid, the method comprising 1) measuring the diameter of the MSCs by estimating the MSC diameter to be about 15 µm (subheading 2.5), 2) seeding 15000 (i.e. 1.5 * 104), 30000 (i.e. 3 x 105), or 60000 (i.e. 6 x 105) MSCs into a hanging drop culture dish and obtaining an MSC spheroid by culturing the MSCs in 25 µl hanging drops for 48 hours (i.e. 2 days) (subheading 2.2), reading on claims 1, 3, 4, and 6. Murphy teaches obtaining MSC spheroids with radii of 251 ± 12 µm and 353 ± 18 µm, respectively for the initial 30000 and 60000 cells per spheroid (Abstract), which equates to diameters of 125.5 ± 6 µm and 176.5 ± 9 µm (i.e. diameter = 2 * radius) and so anticipates claim 5. Murphy teaches that MSCs are regenerative (the first sentence of the first paragraph of the Introduction on page 1), reading on claim 7.
Regarding claim 1, Murphy does not teach wherein the cells are seeded into the culture dish in an initial required number of single cells calculated by the claimed equation.
However, it would have been obvious to try to derive mathematical formula and utilize the claimed equation because: 1) Murphy teaches a need in this art to optimize MSC seeding density because cell viability and metabolism decreases as radii (and so the diameter) of spheroids increases (subheading 3.3 on pages 5-6), 2) Murphy teaches a finite number of identified, predictable potential solutions to the recognized need or problem; in that, there is a known correlation between number of cells in the MSC spheroid and measurements of cell viability (Murphy at Fig. 3), and so 3) a person of ordinary skill in the art could choose from a finite number of identified, predictable solutions, with a reasonable expectation of success (i.e. Murphy’s starting MSC seeding density, number of cells in spheroid, and spheroid radii and thus diameter) to derive the claimed to derive mathematical formula, and utilize said mathematical formula to calculate an optimal MSC spheroid diameter with respect to cell viability and metabolism. See M.P.E.P. § 2143 (E).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 1 and 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (J. R. Soc. Interface (2016), 14: 20160851) in view of Li et al. (Stem Cell Res Ther. (2015) 6(1):55).
The teachings of Murphy are relied upon as set forth above in rejecting claims 1 and 3-7 under 35 U.S.C. § 103. Murphy further teaches expanding and culturing the MSCs prior towards generating spheroids (subheading 2.1), reading in-part on claims 1 and 6.
Regarding claims 1 and 6, Murphy does not teach the elected species of adipose-derived mesenchymal stem cells.
Li teaches that are promising candidates for cell-based therapies and that adipose tissue-derived mesenchymal stem cells (MSCs) have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects relative to bone marrow-derived MSCs (Abstract and Figure 2), reading on claims 1 and 6.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the adipose tissue-derived MSCs of Li for the bone marrow-derived MSCs of Murphy in Murphy’s methods of generating MSC spheroids. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Murphy and Li are in-part directed towards methods of culturing MSCs, and because Li expressly compares the properties of MSCs based upon differing source tissues. The skilled artisan would have been motivated to do so because Li teaches that adipose tissue-derived MSCs have improved proliferative capacity, and so the substitution would be predictably advantageous to generate additional stem cells in the culturing methods of Murphy prior to the seeding and generation of MSC spheroids taught by Murphy.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Affidavit/Declaration
The Declaration under 37 CFR 1.132 filed 7/31/2026 is insufficient to overcome the rejection of claims 1 and 3-7 over Murphy alone and over Murphy in view of Li as set forth in the last Office action because:
It include(s) statements and evidence which amount to an affirmation that the claimed subject matter functions as it was intended to function. This is not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716. The data proffered at points 13-16 of the instant Declaration only affirm the claimed method is operable, which is not germane to considerations of non-obviousness. Applicant bears the burden of showing that any differences between the claims and the prior art are in-fact unexpected and of both statistical and practical significance (see M.P.E.P. § 716.02(b), and Declarant does not clearly set forth what results are expected such as to then persuasively show any unexpected result reasonably commensurate to the scope of the claims
Declarant’s arguments at points 6-12 and 17-22 do not appear to provide any additional factual evidence in support of what amounts to a general allegation of nonobviousness. See M.P.E.P. § 716.01(c)(III), in so much that opinions without factual support to a legal conclusion are not entitled to any weight and are highly unlikely to be of substantial evidentiary value.
The Declaration as a whole does not address any the four pillars of the “obvious to try” rationale of record and maintained above, and so cannot rebut the prima facie case for obviousness of record at this time (see M.P.E.P. § 2143(E)). At this time, there is no clear showing in the record by a preponderance of evidence that the claimed methods yield any unexpected result compared to Murphy and Murphy in view of Li.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Response to Arguments
Applicant's arguments on pages 4-13 of the reply have been fully considered, but not found persuasive of error for the reasons given below. Any reference to the instant Declaration is fully addressed above.
On pages 7-9 of the reply, Applicant alleges that Murphy is deficient by “merely” disclosing a relationship between the number of seeded mesenchymal stem cells (MSCs) and the size of the resulting MSC spheroids under experimental conditions and that Li is deficient for only disclosing (the elected species) of adipose stem cells (ASCs). This is not found persuasive because the claims were rejected under the “obvious to try” rationale and none of Applicant’s arguments address and rebut the four pillars of the “obvious to try” rationale as set forth in M.P.E.P. § 2143(E) and summarized as 1) need in the art, 2) finite number of known and predictable solutions, 3) reasonable expectation of success, and 4) “additional findings” (as a catchall for other pertinent considerations of obviousness).
Applicant’s arguments on pages 10-12 of the reply are not found persuasive, as they rely on the instant Declaration and are fully addressed above. Briefly restated, . the data proffered at points 13-16 of the instant Declaration only affirm the claimed method is operable, which is not germane to considerations of non-obviousness
Conclusion
No claims are allowed. No claims are free of the art.
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 SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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