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 .
Election/Restrictions
Applicant’s election of Group III (claims 10-17) in the reply filed on 04/16/2026 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 1-17 are currently pending.
Claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/16/2026.
Claims 10-17 have been examined on their 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 11, 13, 16-17 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.
Regarding claims 11, 13, 16 and 17, the phrase "such as" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
For examination purposes the limitations following the phrase “such as” are interpreted as optional and thus not required.
Appropriate correction is required.
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.
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.
Claim(s) 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Ge et al. (CN-109234231-A, using a machine translation, previously cited) in view of Malda et al (TRENDS in Biotechnology, 2006) and Sart (American Institute of Chemical Engineers Biotechnology Progress, 2013).
Regarding claims 10-11 and 13, Ge disclose methods of removing adherent cells from a surface of a microparticle suitable for use as a microcarrier particle, wherein the microcarriers comprise gelatin crosslinked by genipin (page 5 embodiment 1, pages 6-7 examples 2-9). Ge disclose providing a composition comprising cell-seeded microcarriers dispersed in PBS (solvent) and contacting this composition with a protease mixture (0.25% pancreatin EDTA) for a sufficient period of time (30 minutes) to enzymatically degrade the microcarriers and release the cells from the microcarrier surface (pages 6-7 examples 2-9). The microcarriers have a diameter of 75-300 µm (page 5 Embodiment 1) which overlaps with the claimed diameter range and thus renders the claimed range obvious (MPEP 2144.05).
Ge are silent with regard to Young’s modulus, microcarrier density in g/cm3, and the coefficient of variation (CoV) of the diameter of the microcarrier.
However, the values of the diameter, elastic modulus, and density of the microcarrier are considered properties that a skilled person looking to improve the microcarriers for cell expansion would inevitably arrive at during routine optimization.
Malda disclose an overview of the microcarrier culture system (abstract) and that microcarrier diameters are typically 100-400 µm, that the size distribution should be as narrow as possible to provide a homogenous culture (variation in size/diameter of the microcarriers should be as low as possible) and their specific density should be slightly higher than that of the culture medium (typically between 1.02 and 1.10) to enable them to be maintained in suspension by gentle agitation (page 299 column 2).
Sart disclose that the biochemical and biomechanical properties of microcarriers can affect stem cell fate (Title, abstract). A microcarrier with a matrix stiffness of 34 kPa (Young’s Modulus) promoted spindle-like shape and osteogenic differentiation of MSCs (page 1357, column 2).
One of ordinary skill in the art would have been motivated to optimize the diameter, elastic modulus (Young’s modulus), density and coefficient of variance for the diameter, and optionally for the Young’s modulus and the density, of the microcarriers used in the method of Ge because Malda and Sart indicate that these are microcarrier properties that are known in the prior art to be suitable and beneficial for the culture of cells. Values for the claimed diameter, elastic modulus and density are known in the prior art to be suitable for microcarriers for cell culture as disclosed by Malda and Sart above. As for the difference pertaining to the CoV of the diameter, it would also be obvious for the skilled person who is looking to improve the microcarriers for cell expansion to consider reducing the CoV of the microcarrier size through routine methods in the art (e.g. cell sorting or microfluidics) and to inevitably arrive at the CoV of the diameter specified in the claims. A coefficient of variance that is 5% or less is also motivated by the teaching of Malda that the size distribution of the microcarriers should be as narrow as possible to provide a homogenous culture. A very narrow size range would provide a monodispersed population of microparticles/microcarriers. One of ordinary skill in the art would have had a reasonable expectation of success because Ge is also using microcarriers that comprise gelatin crosslinked by genipin, the same material and crosslinking as used and claimed by Applicant.
Regarding claim 12, Ge do not specifically indicate that the microparticles are present in a concentration of from 5 to 50% of the composition, but this would have been an obvious feature to include since higher concentrations of microparticles would lead to a composition that was crowded with microparticles and more potential for aggregation of the microparticles in suspension. One of ordinary skill in the art would have been motivated with a reasonable expectation of success to optimize the concentration of the microparticles in suspension to achieve a balanced suspension that allows the microparticles to float without aggregation.
Regarding claim 14, Ge disclose collecting the released cells from the composition and including washing the cells (pages 6-7 examples 2-9). Ge is silent with regard to any residue of the microparticles accompanying the cells and thus the washed and collected cells are deemed to be substantially free of microcarrier residue.
Regarding claims 15-17, Ge disclose wherein the composition is obtained by adding cells and microparticles to a culture medium for a period of time, wherein the initial cell seeding density is 4 x 105 cells/ml and the culturing time of days (page 6 example 2).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to optimize the initial cell seeding density and the culturing time in the method of Ge because the amount and viability of the cells cultured would have been affected by these conditions. “[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) (MPEP 2144.05).
Therefore, the combined teachings of Ge et al, Malda et al and Sart render obvious Applicant’s invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nguyen et al., “Tissue Regeneration of Human Mesenchymal Stem Cells on Porous Gelatin Micro-Carriers by Long-Term Dynamic In Vitro Culture”, Tissue Engineering and Regenerative Medicine (2019) 16(1):19–28.
Nguyen disclose gelatin microcarriers used for the culture of cells having a density of 1.02–1.04 g/cm3, diameter of 130–380 µm (page 21, column 1).
Samsudin et al., “Optimization of ultraviolet ozone treatment process for improvement of polycaprolactone (PCL) microcarrier performance”, Cytotechnology (2017) 69:601–616.
Samsudin disclose that the density of a microcarrier is approximately 1.02–1.04 g/cm3, which is slightly higher than that of the culture medium and that the ideal size for a microcarrier is in the 100–500 um range and narrow size distribution is important to ensure size uniformity and easy maintenance in suspension at low agitation speeds (page 602, column 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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