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 .
Election/Restrictions
Applicant’s election of Invention I, presently claims 1, 3, 6, and 7, in the reply filed on 7/13/2026 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 § 818.01(a)).
Claims 2, 4, 5, 8, and 9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election has been treated as made without traverse in the reply filed on 7/13/2026.
Claims 1, 3, 6, and 7 are under consideration on the merits.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on four applications filed in the European Union on 5/03/2023, 6/05/2023, and 11/29/2023. It is noted, however, that applicant has not filed a certified copy of the foreign applications as required by 37 CFR 1.55.
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.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is 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 7 recites the limitation "the recirculation ratio”, but there is insufficient antecedent basis for this limitation in the claim as the claim from which it depends, claim 1, does not recite any “recirculation ratio”. Correction is required.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In this case, claim 7 depends from claim 1 but claim 1 does not require any step of recirculation. As such, claim 7 fails to further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 10,100,286; Reference A) in view of Kolenda et al. (J Neurooncol (2011), 103:43-58; Reference U) as evidenced by Bionumbers (“Sizes of various cells”, 2022; Reference V).
Kim teaches systems and methods for automatically and continuously dissociating spheres of cells (Abstract). Kim teaches an embodiment comprising 1) providing brain tumor stem cell spheres, 2) passaging the stem cell spheres through a conduit having an inner diameter of 50-250 μm and at a shear stress of about 60 dynes/cm2 (equating to about 0.5-6 Pa) (Column 4, lines 25-58 and Fig. 1; Column 6, lines 19-24), such as to generate single cells (Column 8, lines 22-33; claim 13), reading in-part on claim 1. Kim teaches there is a need in this art when culturing therapeutic stem cells and malignant cancer stem cells (CSCs) to dissociate cell aggregates into single cells once grown to a critical sphere diameter as when the spheres become too large, inadequate nutrient and oxygen supplies can cause premature necrotic cell death which would then negate efforts to expand said stem cells. (Column 1, line 60 through Column 2, line 4), reading on claim 1. Kim as evidenced by Bionumbers teaches that U87 glioblastoma inherently have a size/diameter of 12-14 μm (right column, towards the bottom), reading on claim 1.Kim teaches that the percentage of viable U87 glioblastoma cells post-dissociation is less than 20% tested across three time periods (Fig. 9; Column 4, lines 11-47; Column 8, lines 34-50), reading on claim 3.
Regarding claim 1, Kim does not teach a U87 glioblastoma spheroid/agglomeration diameter range of 30-300 μm. Regarding claim 6, Kim does not teach a U87 glioblastoma spheroid/agglomeration average diameter range of 100-200 μm.
Kolenda teaches methods of culturing glioblastoma cells as spheroids (Abstract). Kolenda teaches that U87 glioblastoma spheroids have a diameter range between 200-250 μm under normoxic conditions and between 100-150 μm under hypoxic conditions (Fig. 3C; detailed methods at page 54, subheading “Cell culturing”), reading on claims 1 and 6. Kolenda teaches that tumor hypoxia has been attributed to play a crucial role in tumorigenesis and therapeutic resistance (Abstract), reading on claims 1 and 6.
Regarding claims 1 and 6, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further culture the U87 glioblastoma spheroids of Kim under either the normoxic or hypoxic conditions of Kolenda to achieve the claimed spheroid/agglomeration diameter ranges. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Kim and Kolenda are directed towards U87 glioblastoma spheroids/agglomerations, because Kolenda teaches detailed methods of culturing U87 glioblastoma spheroids, and because Kolenda teaches that the U87 glioblastoma spheroid diameter depends on the oxygen concentration in the culture methods. The skilled artisan would have been motivated to do so because Kolenda teaches that tumor hypoxia has been attributed to play a crucial role in tumorigenesis and therapeutic resistance, and so the addition of Kolenda’s culture methods would predictably improve the methods of Kim to study the effects of oxygen tension on the single dissociated U87 glioblastoma cells of Kim.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kim and Kolenda as applied to claim 1 above, and further in view of Aidun et al. (WO 2011/104373; provided in the IDS dated 11/21/2024).
The teachings of Kim and Kolenda are relied upon as set forth above.
In view of the indefiniteness rejections above and in the interest of compact prosecution, Kim and Kolenda do not teach the embodiment of any step of recirculation and do not teach wherein the recirculation ratio is between 3 and 10.
Aidun teaches methods and devices for dispersing/dissociating biological material suspended in a liquid, such as cultured animal cells, but the application of compressional and extensional strain (Abstract). Aidun teaches a disperser device comprising a means of recirculating the liquid in flow channel (100) with a pump (page 4, lines 25-27; Figure 2 and page 8, lines 5-11), reading in-part on claim 7. Aidun teaches mixing chamber (101) comprises a transparent wall section for visual inspection of the size distribution of the matter to be dispersed and configured as a recirculation loop, which allows for circulating the assemblies through the same constrictions repeatedly thus making it possible to construct a more compact, simpler and cheaper device in comparison to a linear flow channel (100) configuration and allows for allows for monitoring and controlling the degree of dispersion. (page 20, lines 8-23), reading in-part on claim 7. Aidun teaches controlling the flow of the recirculation configuration by the addition of valves, and that a fluid reservoir may be used to provide fluid when needed to move the dispersed assemblies further in the device (page 21, lines 3-18), reading in-part on the recirculation ratio of claim 7.
Regarding claim 7, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the dissociation device of Kim with the dispersing/dissociating device of Aidun comprising a transparent window and recirculation loop configuration in Kim’s methods. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Kim and Aidun are directed towards devices/systems and methods of dissociating animal cells. The skilled artisan would have been motivated to do so because Aidun teaches that the combination of a transparent window and recirculation loop configuration is predictably advantageous to construct a more compact, simpler, and cheaper device and to monitor and control the degree of dispersion until the desired degree of dispersion is achieved, thus improving upon the methods of Kim.
Regarding the recirculation ratio range of claim 7, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. While Aidun does not teach the claimed recirculation ratio range, Aidun necessarily teaches that any recirculation ratio range is result-effect to both achieve a desired degree of dispersion of the cells and provides an expression motivation to optimize the recirculation ratio by providing additional fluid to move the dispersed assemblies further., the burden is shifted back to establish criticality of the claimed recirculation ratio range by objective evidence over Kim in view of Aidun. Alternatively, repetition of steps previously recited within a claim is on its own not inventive because it merely requires employing the well-known maxim, “If at first you don’t succeed, try, try again.” See Perfect Web Techs., Inc. v. InfoUSA Inc., 92 U.S.P.Q.2d 1849, 1856 (Fed. Cir. 2009). Repeating steps until a desired result is achieved requires only common sense and so is obvious to try, and in the absent of any showing to the contrary, is not inventive. Id. at 1854-55 (citing KSR Int’l Co. v. Teleflex Inc., 82 U.S.P.Q.2d 1385 (U.S. 2007)). See M.P.E.P. § 2143(I)(E). In this case, Aidun makes clear that any recirculation ratio range is related to the express motivation taught by Aidun to achieve a desired degree of dispersion and the movement of the dispersed assemblies within Aidun’s device, and so the claimed recirculation ratio range must be held as prima facie obvious to try absent any showing to the contrary.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
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).
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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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