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 .
Claim Status
Claims 8 and 22-31 were previously canceled and claims 1-7 and 9-21 have been considered 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.
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, which depends from claim 1, recites the limitation “…the cell container has a volume of 0.25 mL to 0.5mL.” Claim 1 describes two containers, the cryopreservation cell container and the separate container to which the cells are transferred. It is not clear to which cell container the claim is referring. Therefore, the scope of “cell container” is unclear. The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973). For the purpose of compact prosecution, the cell container of claim 13 is interpreted as the first cell container, the cell container used for cryopreservation.
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, 7, 9, 11, 14, and 19-20 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Maung et al. (US 2023/0031222 Al, published 02 February 2023) as evidenced by Stemcell Technologies (CryoStor® CS10 product data sheet, 2020).
Regarding claim 1, Maung teaches a system for processing cells which can include a cell culture container, a fluid handling device, and one or more removable cell processing modules for performing one or more cell processing processes (Abstract). Maung teaches PBMCs were cryopreserved in a cryopreservation medium in cell containers (claim 1(i)), then thawed (claim 1 (ii)) (para. [0789]). Maung teaches the cells were washed, resuspended then loaded into the cell processing system (transferred before step (iii)) (para. [0790]). Maung teaches T cells were isolated from the PBMCS, were counted, and aliquoted as 10-20e6 cells per nucleofection reaction (para. [0792]). Maung teaches the cells were resuspended with a Cas9/Ribonucleoprotein (RNP) mix, comprising Cas9 protein mixed with TRAC sgRNA (para. [0792]-[0793]). The RNP mixture reads as comprising genetic material, sgRNA, and a cell manipulation solution, Cas9, to introduce the genetic material into the cells (claim 1(iii)).
Regarding claim 2, Maung teaches the cells were frozen in CryoStor® CS10 cryopreservation medium (para. [0789]). CS10 is a medium suitable for freezing iPSCs or human peripheral blood and comprises 10% DMSO and is a serum free medium, as evidenced by Stemcell Technologies product description. The remaining limitations are listed as optional, as such, are not required by the claim.
Regarding claims 3 and 4, Maung teaches the cells were washed, resuspended in 1 ml buffer before being loaded into the cell processing system (para. [0790]). Since washing does not completely remove the previously media, as evidenced by Stemcell Technologies thawing cells protocol, this step reads as the freezing media and cells were transferred together to the separate container (claim 3). The previously described washing step would remove at least a portion of the freezing media and washing cells properly would not disturb the cell pellet (claim 4) as evidenced by Stemcell Technologies thawing cells protocol. The remaining limitations of claim 4 are listed as optional, as such, are not required by the claim.
Regarding claim 5, Maung teaches T cells were isolated from the PBMCS, were counted, and aliquoted as 10-20e6 cells per nucleofection reaction (para. [0792]). Maung teaches the cells were resuspended with a Cas9/Ribonucleoprotein (RNP) mix, comprising Cas9 protein mixed with TRAC sgRNA (para. [0792]-[0793]). The RNP mixture reads the separate container comprises a cell manipulation solution. The remaining limitations are presented in the alternative, as such, are not required by the claim.
Regarding claim 7, the Cas9/Ribonucleoprotein (RNP) mix of Maung reads as comprising a polynucleotide, sgRNA, and a CRISPR ribonucleoprotein complex, Cas9.
Regarding claim 9, Maung teaches the cells were aliquoted (para. [0792]). Aliquoting cells reads as one or more batches of cells which would require multiple containers.
Regarding claim 11, the claim recites therapeutically administering to processed cells to a subject having a condition, wherein administration of the cells causes a reduction in at least one indication of the condition. These limitations are considered intended use and intended results statements and is not given patentable weight because it does not add structure to the method of processing cells. Therefore, the claim is interpreted the method of claim 1, and is rejected for the same reasons.
Regarding claim 14, Maung teaches the cell processing module, the CARE hardware platform. Maung teaches the cells combined with the RNP mixture were loaded into the CARE electroporator to conduct the TRAC locus editing (para. [0793]). Maung teaches the CARE automated hardware is used for isolation of T cells from fresh and thawed from frozen human PBMCs (para. [0078]).
Regarding claim 19, Maung teaches all engineered cells were cultured in CARE cell
culture consumables for 7 days with T cell culture media, supplemented with IL-2 and IL-15 (para. [0795]). The cell culture consumable reads as a tissue culture plate and culturing T cells in a T cell culture media reads as conditions in which cells multiply.
Regarding claim 20, Maung teaches the cells were resuspended with a Cas9/Ribonucleoprotein (RNP) mix, comprising Cas9 protein mixed with TRAC sgRNA (para. [0792]-[0793]). The Cas9/Ribonucleoprotein (RNP) mix of Maung reads as the cells were contacted with a guide RNA and a Cas protein. The statement directed to the guide RNA and Cas protein editing the cells when plated is considered an intended result statement and is not given patentable weight because it does not add structure to the method of processing cells. Therefore, this statement is not considered limiting.
Thus, the reference anticipates the subject matter of claims 1-5, 7, 9, 11, 14, and 19-20.
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.
Claims 6, 12-13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Maung et al. (US 2023/0031222 Al, published 02 February 2023) as evidenced by Stemcell Technologies (CryoStor® CS10 product data sheet, 2020) as applied to claims 1-5, 7, 9, 11, 14, and 19-20 above, and further in view of Bouaita et al. (US 2017/0020128 A1, published 26 January 2017).
Maung anticipate the subject matter of claims 1-5, 7, 9, 11, 14, and 19-20, and thus, also render them obvious.
Regarding claim 6, Maung does not teach the cells are not washed or centrifuged after thawing the cells.
However, Bouaita teaches the classical process for post-thaw removal of cryoprotectant consists of thaw, spin, and resuspend, followed by removal of the cryoprotectant (para. [0008]). Bouaita teaches a new method for eliminating the necessity of post-thaw wash and spin (para. [0010]). Bouaita teaches this method would be suitable for a variety of living cells to include iPSCs or blood cells (para. [0030]).
Regarding claim 12, Maung does not teach the time between step (ii) and step (iii) is less than 60 minutes.
However, Bouaita teaches in their no-spin method of thawing and recovering cells, wherein the frozen vials are removed from the freezer and immediately placed into a 37°C water bath (para. [0090]). Bouaita teaches once the cells were “semi”-thawed, in approximately one minute, the vial was removed from the water bath and placed under a laminar flow hood before opening (para. [0090]). The point at which the vial is able to be opened is considered where step (iii) would begin. Therefore, Bouaita teaches the time between steps (ii) and (iii) would be approximately one minute, which is less than 60 minutes.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the post-thaw method of Bouaita with the method of processing cells of Maung with a reasonable expectation of success because Maung and Bouaita both teach methods comprising blood cells. One would be motivated to utilize the post-thaw method of Bouaita with the method of processing cells of Maung because Bouaita teaches the classical cell thawing and recovering process is time-consuming and costly, with higher risk of contamination due to additional handling and resuspension of the thawed cells, thus, highlighting the benefits of the new method for post-thaw processing of cells.
Regarding claim 13, Maung does not teach a cell container with a volume of 0.25 to 0.5 mL.
However, Bouaita teaches the 10 million cells are concentrated into 0.25 mL (1 vial), such that the concentration corresponds to 20 million cells/mL, and then, a 0.25 mL freezing solution with 20% DMSO (1 vial) is added into the concentrated cells, thus, the final volume of cell mixture is 0.5 mL (para. [0036]). Thus, is reasonable to expect a cell container with a volume of 0.5 mL would be utilized in the method of Bouaita.
Regarding claim 15, Maung does not teach a cell concentration of 1e6 to 1e7 cells/100uL.
However, Bouaita teaches a method of freezing cells at a concentration of 50 million cells/mL prior to cryopreservation (para. [0069]), which equals 5e6 cells per 100uL. The cell concentration falls within the required range of 1e6 to 1e7 cells/100uL.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Maung et al. (US 2023/0031222 Al, published 02 February 2023) as evidenced by Stemcell Technologies (CryoStor® CS10 product data sheet, 2020) as applied to claims 1-5, 7, 9, 11, 14, and 19-20 above, and further in view of Bouaita et al. (US 2017/0020128 A1, published 26 January 2017) and Laperle et al. (WO 2021/081229 A1, published 29 April 2021).
Maung anticipate the subject matter of claims 1-5, 7, 9, 11, 14, and 19-20, and thus, also render them obvious.
Regarding claim 10, Maung does not teach wherein the cells comprise iPSCs.
However, the cryopreservation of iPSCs as well as PBMCs are well-known in the art. Bouaita teaches the method of cryopreservation and thawing cells method would be suitable for a variety of living cells to include iPSCs or blood cells (para. [0030]).
Additionally, Laperle teaches contacting iPSCs with genetic material and a cell manipulation solution (Abstract). Laperle teaches clonal cell lines were generated with a single copy GDNF construct inserted in the AAVS1 safe landing site, including inducible expression of GDNF (Abstract). Laperle teaches the utilization of iPSCs provide the benefit of clonal expansion capabilities, where one can uniformly introduce genetic constructs, including inducible expression systems or deploying genetic editing techniques such as CRISPR (para. [0017]). The teachings of Laperle would necessarily comprise a cell manipulation solution as Laperle teaches introducing genetic material into cells.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the iPSCs of Laperle in the method of Maung in view of Bouaita with a reasonable expectation of success because Bouaita teaches both PBMCs and iPSCs can be thawed successfully following cryopreservation and Laperle teaches iPSCs can be genetically modified. One would be motivated to utilize the iPSCs of Laperle in the method of Maung in view of Bouaita because thawing cryopreserved iPSCs followed by genetic modification was a well-known process at the time of filing, thus making it an obvious cell to use in the method of Maung.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claims 16-18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Maung et al. (US 2023/0031222 Al, published 02 February 2023) as evidenced by Stemcell Technologies (CryoStor® CS10 product data sheet, 2020) as applied to claims 1-5, 7, 9, 11, 14, and 19-20 above.
Maung anticipate the subject matter of claims 1-5, 7, 9, 11, 14, and 19-20, and thus, also render them obvious.
Regarding claim 16, Maung teaches the system comprises a plurality of removable cell processing modules, comprising a module for performing transfection and a module for performing cryopreservation (para. [0389]).
Maung does not specifically teach the cryopreservation of a portion of the cells following the cells being contacted with the genetic material.
However, it would have been obvious to one of ordinary skill in the art to cryopreserve a portion of the cells in the method of Maung with a reasonable expectation of success because Maung teaches the cell processing system comprises a module for cryopreservation of cells. One would be motivated to cryopreserve a portion of the cells in the method of Maung because cryopreservation of cells facilitates the safe and protective long term storage and viability of cells, as evidenced by Stemcell Technologies product description.
Regarding claim 17, Maung teaches the cells were resuspended with a Cas9/Ribonucleoprotein (RNP) mix, comprising Cas9 protein mixed with TRAC sgRNA (para. [0792]-[0793]). The Cas9/Ribonucleoprotein (RNP) mix of Maung reads as the cells were contacted with a guide RNA and a Cas protein. The remaining limitations of claim 17 are listed as optional, as such, are not required by the claim.
Regarding claim 18, the claim recites wherein the cryopreserved cells are shipped frozen to a different location. This limitation is considered intended use and is not given patentable weight because it does not add structure to the method of processing cells. Therefore, the claim is interpreted the method of claim 17, and is rejected for the same reasons.
Regarding claim 21, Maung teaches the system comprises a plurality of removable cell processing modules, comprising a module for performing transfection and a module for performing cryopreservation (para. [0389]).
Maung does not specifically teach the cryopreservation of the cells following the cell expansion.
However, it would have been obvious to one of ordinary skill in the art to cryopreserve the cells following expansion in the method of Maung with a reasonable expectation of success because Maung teaches the cell processing system comprises a module for cryopreservation of cells. One would be motivated to cryopreserve the cells following expansion in the method of Maung because cryopreservation of cells facilitates the safe and protective long term storage and viability of cells, as evidenced by Stemcell Technologies product description. The remaining limitations of claim 21 are listed as optional, as such, are not required by the claim. Furthermore, the limitations directed to shipping the cryopreserved cells is considered an intended use statements and is not given patentable weight because it does not add structure to the method of processing cells.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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