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 I, claims 1-12 and 16-20 in the reply filed on 05/27/2026 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Claims 14-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/27/2026.
Status of the Claims
Claims 1-12 and 14-20 are currently pending.
Claims 1, 3-12, and 14-15 are amended.
Claims 14-15 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claim 13 is cancelled.
New claims 16-20 have been added.
Claims 1-12 and 16-20 have been considered 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.
Claim 19 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 19 contains the trademark/trade name AGE.CR1™ and EB.66™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe specific cell lines which should be described in generic terms and, accordingly, the identification/description is indefinite.
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 1-2, 4-8, 10, 12, and 16-19 are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by Lee et al (US20110190162 A1).
With regards to claim 1, Lee teaches a method of performing a bioproduction process comprising production of a transformed cell population ([0059 and Fig. 4) comprising the step of culturing a cell population at least partially embedded in a hydrogel matrix forming a 3D structure (See Fig. 4). Lee teaches wherein the hydrogel matrix comprises a transforming agent (Fig. 4 and [0059]). Lee teaches wherein the growth of the cell population at least partially embedded in the hydrogel matrix results in the transformation of at least a part of the cell population by uptake of the transforming agent (See [0059] and Fig. 4).
Regarding claim 2, Lee teaches wherein the hydrogel structure has been obtained by depositing one or more bioink compositions comprising a biomaterial capable of forming a hydrogel, in this case alginate, mixed with a retroviral transforming agent and a biomaterial, in this case alginate, mixed with a cell population in a controlled 3D shape to obtain a cellularised structure (See Fig. 4 and [0059]).
Regarding claim 4, Lee teaches the formation of a hydrogel structure by first layering a retroviral transforming agent-alginate mixture and subsequently layering a cell-alginate mixture which would constitute a first region comprising the cell population in a hydrogel matrix and a second region comprising the transforming agent in the hydrogel matrix ([0059] and Fig. 4).
Regarding claim 5, Lee teaches wherein the hydrogel structure has been obtained by depositing one or more of a first bioink composition including the alginate capable of forming a hydrogel structure and a cell population which is incubated in complete medium for 24 hours ([0057]) to form a first region of a hydrogel structure and one or more additional bioink compositions containing the alginate and a transforming agent to a second region of the hydrogel structure ([0057]-[0059] and Fig. 4).
Regarding claim 6, Lee teaches that the transforming agent is a virus, more specifically a retrovirus ([0057]-[0059]).
Regarding claim 7, Lee teaches the inclusion of an additive, polybrene, “to increase transfection efficiency” ([0057]), which meets the limitations of the additive being a transfection reagent which neutralizes negative charges on viral particles and cell surfaces which results in an increase in transfection efficiency and an increased bioavailability of the transforming agent, in this case the retrovirus, ([0057]).
Regarding claim 8, Lee teaches that the cell population comprises one or more cell lines, NIH3T3 and/or CHO-K1 ([0057]-[0059]).
Regarding claim 10, Lee teaches that the deposited bioink (alginate) solution is consolidated by cross-linking the biomaterials capable of forming a hydrogel ([0035]).
Regarding claim 12, Lee teaches wherein the growth of the cells in the hydrogel results in the transformation of at least part of the cell population after a predetermined amount of time which is at least after 3-4 days in culture ([0057]-[0059]).
Regarding claim 16, Lee teaches the formation of a hydrogel structure by first layering a retroviral transforming agent-alginate mixture (bioink) and subsequently layering a cell-alginate mixture (bioink) which would constitute a first region/layer comprising the cell population in a hydrogel matrix and a second region/layer comprising the transforming agent in the hydrogel matrix ([0059] and Fig. 4). Further, Fig. 4 demonstrates that the deposited materials are in a liquid cell culture medium (Fig. 4).
Regarding claim 17, Lee teaches the formation of a hydrogel structure by simultaneously depositing a cell and alginate mixture (bioink) to form a first layer in a liquid cell culture medium ([0057]-[0059] and [0042]) and then depositing a retroviral transforming agent-alginate mixture (bioink) forming a second region/layer comprising the transforming agent in the hydrogel matrix ([0059] and Fig. 4). Further, Fig. 4 demonstrates that the deposited materials are in a liquid cell culture medium (Fig. 4).
Regarding claim 18, Lee teaches the inclusion of an additive, polybrene, “to increase transfection efficiency” ([0057]), which meets the limitations of the additive being a transfection reagent because polybrene is a positively charged reagent which neutralizes negative charges on viral particles and cell surfaces which results in an increase in transfection efficiency and an increased bioavailability of the transforming agent, in this case the retrovirus, ([0057]).
Regarding claim 19, Lee teaches that the cell populations is mammalian cells and is one or more of cell lines a CHO, more specifically CHO-K1, or HEK cells ([0036] and [0057]-[0059]).
Therefore, Lee 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 3 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US20110190162 A1), as applied to claims 1-2, 4-8, 10, 12, and 16-19 above, and in further view of Grant et al (US20220175534 A1).
Regarding claims 3 and 9, the limitations of the independent claim 1 are taught above.
Regarding claim 3, Lee teaches that the method comprises providing one or more bioink compositions comprising alginate, a cell population in a liquid culture medium and a transforming agent, wherein providing comprises incubating the bioink composition at a predetermined temperature for a predetermined period of time such that the viscosity is compatible with printing (Fig. 4, [0057]-[0059], [0065]). Lee teaches that obtaining the hydrogel structure forming a 3D structure by depositing the bioink composition in a controlled 3D shape to obtain a cellularised structure ([0057]-[0059], Fig. 4), wherein the bioink composition has been obtained by mixing one or more solutions comprising one or more biomaterials capable of forming a hydrogel and cells in a liquid culture medium (Fig. 4, [0042]).
Regarding claim 9, Lee teaches that the method comprises obtaining a 3D structure (See Fig. 4).
Lee does not teach that the bioink is deposited by additive manufacturing, also known as a bioprinter as required by claim 3. Lee does not teach that the method comprises obtaining a 3D structure by additive manufacturing or wherein the additive manufacturing comprises depositing a composition at a rate below 0.2 mm/s as required by claim 9.
However, Grant teaches a custom bioprinter assembly ([0301]).
Regarding claim 3, Grant teaches a custom bioprinter assembly which has multiple motors controlling the X, Y, and Z axis containing an error of movement less than 0.1 µm ([0301]) which is used for bioprinting various hydrogels including collagen and alginate ([0211]).
Regarding claim 9, Grant teaches obtaining a 3D structure comprising a hydrogel matrix by additive manufacturing (bioprinting) ([0297]). Further, Grant teaches that using additive manufacturing methods like extrusion-based bioprinting creates unique fabrication capabilities for patient-specific treatments ([0297]). Further, Grant teaches that the print rate can be from 0.1 mm/s – 0.2 mm/s ([0176]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method including depositing the hydrogel composition taught by Lee with the additive manufacturing method of depositing the hydrogel composition taught by Grant to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Grant teaches that using additive manufacturing methods like extrusion-based bioprinting creates unique fabrication capabilities for patient-specific treatments ([0297]). One of ordinary skill in the art would have a reasonable expectation of success when combining Lee with Grant because Lee teaches the method completed with manual depositing of the hydrogel whereas Grant provides a custom bioprinter assembly which has multiple motors controlling the X, Y, and Z axis containing an error of movement less than 0.1 µm ([0301]) which is used for bioprinting various hydrogels including collagen and alginate ([0211]).
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.
Claims 11 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US20110190162 A1), as applied to claims 1-2, 4-8, 10, 12, and 16-19 above, and in further view of Deplano et al (US20140030762 A1).
Regarding claim 11, the limitations of the independent claim 1 are taught above.
Lee does not teach wherein the hydrogel matrix comprises alginate and fibrin and/or wherein the cell culture embedded in the hydrogel matrix forming the cellularised product is cultured in a bioreactor as required by claim 11.
However, Deplano teaches about a bioreactor used to culture hydrogel based cellularised materials (abstract, [0045]).
Regarding claim 11, Deplano teaches that the hydrogel can contain alginate and fibrin ([0044]), and that “the bioreactors according to the invention are particularly advantageous for cell culture on a three-dimensional support, notably on porous hydrogels” ([0126]) because hydrogels “have very great potential when it comes to cell culture in three dimensions and they are used as replacement for many materials usually used in cell culture” ([0018]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method including incubating the hydrogel compositions within a typical cell culture chamber taught by Deplano with the method culturing a hydrogel composition within a bioreactor taught by Deplano to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Deplano teaches “the bioreactors according to the invention are particularly advantageous for cell culture on a three-dimensional support, notably on porous hydrogels” ([0126]). One of ordinary skill in the art would have a reasonable expectation of success when combining Lee with Deplano because Deplano teaches the necessary information to culture hydrogels containing cells.
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.
Claims 20 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US20110190162 A1), as applied to claims 1-2, 4-8, 10, 12, and 16-19 above, and in further view of Ledo et al (Acta Biomater. 2020).
Regarding claim 20, the limitations of the independent claim 1 are taught above.
Lee does not teach wherein the method comprises harvesting a cellular product wherein the cellular product comprises a cellular product exclusively or more effectively produced by transformed cells, wherein the step of harvesting is during the culture step or at the end of the culturing step and wherein the cell product is optionally a cell population comprising transformed cells as required by claim 20.
However, Ledo teaches about transfection of mesenchymal stem cells within hydrogels and teaches that the MSCs transfected within the hydrogels showed higher expression of chondrogenic markers compared to MSCs transfected in 2D prior to encapsulation (abstract).
Regarding claim 20, Ledo teaches that at desired time points cells were retrieved from the hydrogel matrix containing the transforming agent and the cells were released from the hydrogel and pelleted before performing testing on the cells (pg. 5 last para spanning pg. 6 para 1-2).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method including incubating cells and a transforming agent within a hydrogel composition taught by Lee with the method of harvesting cells from a transforming agent containing hydrogel composition taught by Ledo to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because harvesting cells from a hydrogel for further experimentation/testing is routine and conventional in the art and Ledo teaches a similar method of transforming cells using a transforming agent within a hydrogel, including subsequent harvesting of the cells. One of ordinary skill in the art would have a reasonable expectation of success when combining Lee with Ledo because harvesting cells from a hydrogel is a routine and conventional activity in the art.
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.
Conclusion
No claims are allowed.
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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