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 .
Status of the Claims
Claims 1-5 and 7-13 are currently pending.
Claims 1, 2, and 4 are amended.
Claims 8-11 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 12 and 13 are newly added.
Claims 1-5, 7, and 12-13 have been considered on the merits.
Withdrawn Objections/Rejections
The objections made onto claims 2 and 4 have been withdrawn in light of the amendments made on 04/09/2026.
The 112(b) rejection made onto claim 6 is withdrawn in light of the amendments made on 04/09/2026.
New Rejections Necessitated by Amendment
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.
Claim 13 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 13 recites the phrase “wherein performing the cell culture includes spreading the crosslinked culture colloid on a surface of a culture dish until a height of the crosslinked culture colloid is 10 mm to 50 mm, and culturing the cells with 0.1 mL/cm2 to 0.5 mL/cm2 of culture medium”, which renders the claim indefinite. The claim requires a first step of providing a culture colloid with cells, a second step of performing crosslinking treatment to the culture colloid “embedding the cells to obtain a crosslinked culture colloid”, and finally performing a cell culture. The indefinite limitation is a wherein clause which acts to limit the final step of “performing cell culture” which is unclear. By the step of performing cell culture the cells have already been embedded within the crosslinked culture colloid, thus it is unclear how the subsequent step of “performing cell culture” is performed by spreading a culture colloid which has already been crosslinked. Crosslinking typically imparts a rigidity to the culture colloid which does not allow it to spread. It is not clear if applicant intended to limit the step of performing the crosslinking treatment to including spreading the culture colloid prior to crosslinking. Appropriate clarification is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mazrouei et al (Scientific Reports, 2020), as evidenced by Kotelevets et al (Cancers, 2023).
Regarding claim 1, Mazrouei teaches providing a culture colloid mix with cells (pg. 9, para 4), performing a crosslinking treatment to the culture colloid with the cells so that the culture colloid is a spherical structure and the cells are suspended in the crosslinked culture colloid (pg. 9, para 4), and performing cell culture (pg. 9, para 4). Mazrouei teaches that the spherical culture colloid is crosslinked from a 3D printer, i.e. a dispensing machine, using syringe mixing (pg. 9, para 4).
Regarding claim 2, Mazrouei teaches that the culture colloid is alginate and nanofibrillar cellulose (pg. 9, para 4).
Regarding claims 3-4, Mazrouei meets the limitations of claim 3 requiring that the culture colloid further includes a cell growth promoter, and further the limitations of claim 4 wherein the cell growth promoter is selected from a group including extracellular vesicles as evidenced by Kotelevets et al. Mazrouei teaches that the cells included in the culture colloid mix are human colon cancer cells (pg. 9, para 3) and Kotelevets provides evidence that human colon cancer cells intrinsically produce extracellular vesicles (EVs). Kotelevets states that EVs are released by almost all cell types and the ones released by colon cancer cells can be employed for early detection, demonstrating that colon cancer cells also secrete EVs (abstract). Thus, the human colon cancer cells of Mazrouei would intrinsically secrete EVs which would be present in the culture colloid of Mazrouei.
Regarding claim 5, Mazrouei teaches that the cells used are Human colon cancer cells, which are a known type of epithelial cell (pg. 9, para 3).
Regarding claim 12, Mazrouei teaches that the diameter of the spherical structure is about 1 mm (see Fig. 2. A).
Therefore, Mazrouei anticipates the claims.
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.
Claims 1-5, 7, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Mazrouei et al (Scientific Reports, 2020), in view of Voytik-Harbin et al (US20120094376 A1), referred to as Harbin.
Regarding claim 7, the limitations of independent claim 1 and dependent claims 2-5 and 12 are taught by Mazrouei above.
Mazrouei does not teach that the storage modulus of the culture colloid is 1000-5000 Pa as required by claim 7.
However, Harbin teaches a method of a 3D culture through providing a culture colloid mixed with cells ([0092]), performing a crosslinking treatment to the culture colloid mixed with cells thereby embedding and suspending the cells in the crosslinked colloid ([0098]), and then performing cell culture with the embedded cells in the crosslinked colloid ([0115]).
Regarding claim 2, Harbin also teaches that the culture colloid contains collagen ([0001]) and hyaluronic acid ([0112]).
Regarding claims 3-4, Harbin also teaches that the culture colloid further comprises a cell growth promoter including collagen ([0001]), extracellular matrix ([0024]), Fibronectin, laminin, and/or growth factors ([0111]).
Regarding claim 5, Harbin also teaches that the cells are mammalian or human cells ([0120]) and can be fibroblasts, endothelial cells, epithelial cells ([0092]), or mesenchymal stem cells ([0213]).
Regarding claim 7, Harbin teaches that the modulus of the culture colloid can be from 0.5 to 40 kPa, which encompasses the entire claimed range of 1000-5000 Pa ([0010]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the 3D cell culture colloid method taught by Mazrouei with the storage modulus taught by Harbin to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Harbin attributes the storage modulus to a fibril area fraction ([0010]) and Mazrouei demonstrates the culture colloid is formed using fibrillar cellulose (pg. 8, para 3). One of ordinary skill in the art would have a reasonable expectation of success when combining Mazrouei with Harbin because both Mazrouei and Harbin demonstrate methods of forming 3D culture colloids which are crosslinked.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Voytik-Harbin et al referred to as Harbin (US20120094376 A1), in view of Mazrouei et al (Scientific Reports, 2020).
Regarding claim 13, Harbin teaches a method of a 3D culture through providing a culture colloid mixed with cells ([0092]), performing a crosslinking treatment to the culture colloid mixed with cells thereby embedding and suspending the cells in the crosslinked colloid ([0098]), and then performing cell culture with the embedded cells in the crosslinked colloid ([0115]).
Harbin does not teach that the culture colloid is on a surface of a culture dish with a height of 10-50 mm, nor that culturing the cells with specifically 0.1 mL/cm2 to 0.5 mL/cm2 of culture medium as required by claim 13.
However, Mazrouei teaches a similar embodiment to that of Harbin. Mazrouei teaches that using a culture dish with the size of 15 mm x 15 mm x 3 mm and filling the culture dish with enough colloid to adequately fill this size of crosslinked culture colloid (See Fig. 4B, and pg. 9, para 1). Further, Mazrouei teaches culturing this crosslinked cultures with cell culture media in an incubator (pg. 9, para 1 and 4).
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. ___, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In the present situation, rationales A, B, D, and E are applicable. The modification of Harbin et al with Mazrouei et al represent combining prior methods to yield predictable results, substitution for one known element for another, and choosing from a finite number of identified, predictable results. Specifically, the limitation of performing the cell culture with a crosslinked culture colloid having a height of between 10-50 mm is obvious to try using any culture dish in the art due to Mazrouei’s teaching of filling the 15 mm x 15 mm x 3 mm culture dish to form the crosslinked culture colloid (pg. 9, para 1 and 4). Additionally, the claimed culturing the cells with specifically 0.1 mL/cm2 to 0.5 mL/cm2 of culture medium provides a known culture technique of providing crosslinked cell culture with culture medium in a typical range which would be obvious to try. The teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, Harbin and Mazrouei render the claims obvious.
Response to Arguments
Applicant’s arguments, see Remarks, pg. 5-8, filed 04/19/2026, with respect to the rejection(s) of claims 1-7 under 35 U.S.C. 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Mazrouei et al, Harbin et al, and a combination of Mazrouei and Harbin.
Conclusion
No claims are allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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