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 .
Priority
The instant application is a continuation of US Application No. 17/093943, filed 10 November 2020 (now US Patent No. 12163146 B2, filed 10 December 2024). Acknowledgement is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 62/933575, filed 11 November 2019.
Status of the Claims
Instant claims 1-19, of record 06 November 2024, are pending. Therefore, prosecution on the merits commences for claims 1-19.
Information Disclosure Statement
The listing of references in the Specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the Specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of
browser-executable code in the listing of references on Pages 44-46. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
It is of note that the recitation of “nanostring.com” in Pages 18 and 20 is permissible because the reference to the website is limited to the top-level domain name without any prefix.
Claim Objections
Claims 1 and 18 are objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “CAR-T cell” in method step (g) instead of “CAR T-cell”, which is otherwise utilized throughout the claim language.
Appropriate correction is required.
Regarding claim 18: The instant claim is objected to for reciting “CAR-T cell” in Lines 1-2 instead of “CAR T-cell”, which is otherwise utilized throughout the claim language.
Likewise, the instant claim is further objected to for reciting “CAR-T manufacturing product” in Line 2 instead of “CAR T manufacturing product” to better align with the formatting utilized throughout the claim language.
Appropriate correction is required.
Claim Interpretation
The claim language utilizes the transitional term of “including” which is synonymous with “comprising”. See MPEP § 2111.03. Therefore, the transitional term is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.
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 3-4 and 18-19 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 3-4: Instant claim 3 recites the limitation "the T-cell culture" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there are multiple recitations of T-cell cultures within parent claim 1, including a pre-modified T-cell culture and an activated T-cell culture. Therefore, the metes and bounds of the claim cannot readily be determined, rendering the scope of the claim indefinite. See MPEP § 2173.05(e).
Instant claim 4 is included within the rejection because it is dependent upon instant claim 3 and does not correct the deficiencies of the parent claim.
Appropriate correction is required.
Regarding claim 18: The instant claim recites the limitation, “wherein step (h) is performed with a sample input of CAR T-cells of the CAR T-cell culture, a CAR T manufacturing product, or nucleic acids”. The scope of the claim is indefinite, as it is unclear how a sample input of nucleic acids in step (h) results in the determination of one or more molecular characteristics of a CAR T-cell culture, wherein the claim requires a CAR T-cell product. Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim.
Appropriate correction is required.
Regarding claim 19: The instant claim recites the limitation, “wherein step (a) is performed with a sample input of sorted T-cells of the pre-modified T-cell culture, whole blood, or nucleic acids”. The scope of the claim is indefinite, as it is unclear how a sample input of nucleic acids in step (a) results in the determination of one or more molecular characteristics of a pre-modified T-cell culture, wherein the claim ultimately requires a CAR T-cell product. Therefore, the ordinary artisan cannot readily determine the metes and bounds of the claim.
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.
Claims 1-10, 12-13, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kaiser et al (US 2017/0037370 A1) as evidenced by Jakubzick et al (Nature Reviews Immunology, 2017), in view of Masquelier et al (US 2019/0002814 A1, of record on IDS filed 13 March 2025).
Kaiser et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Masquelier et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 1 and 8-10: Kaiser et al disclose an automatic process for the generation of genetically modified T cells that is performed in a closed and sterile cell culture system, wherein the T cells may be genetically modified to express a chimeric antigen receptor (CAR) on their cell surface (Abstract; Paragraphs [0037], [0070]-[0071], [0108]-[0109]). Kaiser et al further disclose that the CAR comprises an extracellular domain, a transmembrane domain, and at least one intracellular signaling domain (Paragraph [0108]).
As such, Kaiser et al disclose that, in order to automatically generate CAR T cells, a patient blood sample comprising T cells is first introduced into a chamber of the closed and sterile culture system (Paragraphs [0065], [0079]). The sample is then centrifugated, resulting in the separation of erythrocytes and platelets from other cells including the T cells (Paragraphs [0065], [0071]). Next, magnetic separation of the T cells is performed using antibodies coupled to magnetic beads specific for markers of T cells – such as CD3 and CD28 – by conducting the labeled cells through a magnetic unit within the separation column of the device, resulting in an enrichment of said T cells (Paragraphs [0065], [0068]-[0071]). After automatically moving the separated T cells to a cultivation chamber of the device, said cells are set at a given density and activated by using modulatory agents (Paragraphs [0066], [0071], [0079]-[0081]). After activation, said T cells are genetically modified, wherein the genetic modification includes said T cells being transduced with a lentiviral vector comprising a polynucleotide sequence encoding for a CAR (Paragraphs [0067], [0071], [0074]-[0075], [0109]). After genetic modification, said CAR T cells are expanded under shaking conditions (Paragraphs [0067], [0071]). Finally, the cultured CAR T cells are washed by centrifugation, concentrated, and harvested (Paragraph [0067], [0114]).
Kaiser et al further disclose activation markers of the T cells are measured prior to being activated and 24 hours post-activation (Paragraphs [0054], [0114]; Figure 2).
Kaiser et al further disclose that, in order to ensure the T cells are cultured in optimal conditions, the cell density, glucose, or pH can be measured remotely periodically throughout the culture process (Paragraphs [0060], [0114]; Figure 6).
Kaiser et al do not disclose that the cell density, glucose, or pH of the culture is automatically optimized based on a molecular characteristic of the T cell culture, as required by instant claim 1.
Masquelier et al, however, disclose automated multi-module cell editing instruments that automate multiple edits into nucleic acid sequences inside one or more cells, and methods of using the automated multi-module cell editing instruments thereof (Abstract; Paragraph [0019]).
As such, Masquelier et al disclose an embodiment wherein the automated multi-module cell editing instrument comprises a housing configured to comprise the following modules: a receptacle configured to receive cells; at least one receptacle configured to receive a nucleic acid backbone and an editing cassette; a nucleic acid assembly module configured to a) assemble the backbone and editing cassette, and b) de-salt assembled nucleic acids after assembly; a growth module configured to grow the cells and measure optical density (OD) of the cells; a filtration module configured to concentrate the cells and render the cells electrocompetent; a transformation module comprising a flow-through electroporator to introduce the assembled nucleic acids into the cells; a combination growth, recovery, and editing module configured to allow the cells to recover after electroporation in the transformation module and to allow the assembled nucleic acids to edit nucleic acids in the cells; and a processor configured to operate the automated multi-module cell editing instrument based on user input and/or selection of an appropriate controller script (Paragraphs [0014], [0217]).
With that, Masquelier et al disclose that the growth module includes a temperature-controlled rotating growth vial, a motor assembly to spin the vial, a spectrophotometer for measuring, e.g., OD in the vial, and a processor to accept input from a user and control the growth rate of the cells. As such, the growth module automatically measures the OD of the growing cells in the rotating growth vial continuously or at set intervals, and controls the growth of the cells to a target OD and a target time as specified by the user. That is, the methods and devices described by Masquelier et al provide a feedback loop that monitors cell growth in real time, and adjusts the temperature, speed, and/or direction of rotation of the rotating growth vial in real time to reach the target OD at a target time specified by a user (Paragraphs [0016], [0140]-[0141]).
Masquelier et al further disclose alternate embodiments of the automated multi-module cell editing instrument, wherein other measures of cell density and physiological state are automatically measured within the growth module rather than optical density, including released enzymes (Paragraph [0299]).
Therefore, it would have been prima facie obvious to have modified the method of Kaiser et al such that the glucose level or pH of the cell culture is automatically optimized in response to the protein expression of the cultured T cells, as suggested in Masquelier et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to have an automated system that can optimize culture conditions in real-time based on feedback provided by the cultured cells, and would have had a reasonable expectation of success given that Masquelier et al disclose the automated adjustment of cell culture conditions following data automatically collected by sensors within the culture device – including enzyme (protein) expression – and Kaiser et al already suggest the remote monitoring of the glucose level and pH of the culture, as well as the protein expression of the cultured T cells. See MPEP § 2143(I)(G).
Consequently, Kaiser et al as modified by Masquelier et al render obvious a method of automatically editing a T cell culture to express a CAR, wherein a baseline protein expression is first measured in T cells introduced into the automated closed and sterile culture system (instant step (a)), wherein the T cells are then activated, genetically modified via the introduction of a CAR having an extracellular domain, a transmembrane domain, and at least one intracellular signaling domain comprised within a lentiviral vector (instant steps (c)-(d)) (claims 8-9), allowed to expand (instant step (e)), and then be concentrated (instant step (f)) and harvested (instant step (g)). As the protein expression of the T cells is periodically monitored throughout the culture – including T cell activation markers (claim 10) – with the data creating a feedback loop to automatically adjust the glucose level or pH of the culture media in response to the protein expression, (instant steps (b), (h)-(i)), this therefore renders obvious the method of instant claim 1.
Regarding claim 2: Following the discussion of claim 1, Kaiser et al further disclose that about 100 million CAR T cells can be harvested (Paragraphs [0058], [0061], [0064], [0114]) This therefore reads on the method of the instant claim.
Regarding claims 3-4: Following the discussion of claim 1, Kaiser et al further disclose an embodiment of the invention wherein a buffy coat from a healthy donor is connected to the tubing set installed on the automated device and naïve and central memory T cell subsets are enriched using a CD62L reagent. The enriched cells are then placed in the culture chamber, activated, transduced on with a lentiviral vector encoding the green fluorescent protein, and expanded. The frequency of the cell subsets is measured throughout the process, wherein the cell subsets include: T cells, B cells, Monocytes, NK cells, NK T cells, and granulocytes. After eleven days of culture and in the final harvest sample, the cell product is composed of over 95% of T cells (Paragraph [0064]; Figure 10).
Kaiser et al further disclose the activation of the T cells via anti-CD3 and anti-CD28 antibodies immobilized on the surface of magnetic beads (Paragraphs [0065], [0068]-[0071]). Kaiser et al also disclose that activation may occur via the co-culture of the T cells with antigen presenting cells or artificial antigen presenting cells (Paragraph [0066]).
Therefore, the mixed population of the enriched cell culture containing monocytes reads on the method of the instant claims, as monocytes are inherently antigen-presenting cells (Jakubzick et al, Pages 349-350). Consequently, the enriched T cell culture comprises at least one accessory cell (claim 3), wherein the accessory cell comprises a monocyte and antigens for a T cell receptor comprising CD28 (claim 4).
Regarding claims 5-7: As aforementioned in the discussion of claim 1, Kaiser et al disclose the activation of the T cells via modulatory agents. Kaiser et al further disclose that the modulatory agents include antibodies (claim 5) coupled to magnetic beads (claim 7) specific for markers of T cells – such as CD3 and CD28 (claim 6) (Paragraphs [0028], [0056], [0071], [0093], [0104], [0106]). This therefore reads on the method of the instant claims.
Regarding claim 12: Following the discussion of claim 1, Masquelier et al further disclose adjusting the temperature of the cell culture in response to the cell data (Paragraphs [0014], [0016], [0217], [0299]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 13: Following the discussion of claim 1, Kaiser et al further disclose that the extracellular domain of the CAR comprises a signal peptide, an antigen binding domain, and a spacer (Paragraphs [0103]-[105], [0108]-[109]). This therefore reads on the method of the instant claim.
Regarding claim 18: As aforementioned in the discussion of claim 1, Kaiser et al as modified by Masquelier et al teach that method step (h) is performed on a sample of the CAR T cells from culture. This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 19: As aforementioned in the discussion of claim 1, Kaiser et al as modified by Masquelier et al teach that method step (a) is performed on a sample of sorted T cells. This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Claims 1-13 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kaiser et al (US 2017/0037370 A1) as evidenced by Jakubzick et al (Nature Reviews Immunology, 2017), in view of Masquelier et al (US 2019/0002814 A1, of record on IDS filed 13 March 2025), and further in view of Fraietta et al (Nat Med, 2018, of record).
The discussion of Kaiser et al as modified by Masquelier et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Kaiser et al as evidenced by Jakubzick et al and as modified by Masquelier et al render obvious claims 1-10, 12-13, and 18-19. Fraietta et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 11: Following the discussion of claim 1 above, Kaiser et al further disclose an embodiment wherein the manufactured gene-modified T cells are analyzed for the percentage of transduced cells and the level of transgene expression per transduced cells (Paragraph [0061]; Figure 7).
With that, Masquelier et al further disclose that the automated methods can be used to generate libraries of living cells of interest with desired genomic changes (Paragraph [0005]).
The combination of Kaiser et al and Masquelier et al fail to teach the determination of at least 500 gene expressions, as required by instant claim 11.
Fraietta et al, however, perform genomic, phenotypic, and functional evaluations to identify determinants of patient response to CAR-T therapy (Abstract).
As such, in one embodiment of the experiment, Fraietta et al disclose the gene expression profiles of CAR T cells generated from patients with advanced, heavily pretreated and high-risk chronic lymphocytic leukemia who received at least one dose of CD19-directed CAR-T cells (Pages 2 and 4). Patients in complete remission (CR) and a small subset of partially responding patients with highly active T cell products (PRTD) had markedly different profiles from those generated from partially responding (PR) and nonresponding (NR) patients (Figure 2; Supplementary Table 3). The disclosed expression profiles in the supplemental table of Fraietta et al examine at least 500 gene expressions.
Therefore, it would have been prima facie obvious to have modified the combined method of Kaiser et al and Masquelier et al to include the generation of gene expression profiles, as detailed in Fraietta et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to better identify the mechanisms of therapeutic success and failure within patient-derived CAR T cells (Fraietta et al: Abstract), and would have had a reasonable expectation of success given the combined protocols of Kaiser et al (Paragraphs [0065], [0071]; Figures 2 and 6), Masquelier et al ([0014], [0016], [0140]-[0141], [0217], [0299]), and Fraietta et al (Pages 10-11). See MPEP § 2143(I)(G).
Consequently, Kaiser et al as modified by Masquelier et al and Fraietta et al render obvious a method of automatically editing a T cell culture to express a CAR, wherein at least 500 gene expressions are determined. This therefore renders obvious the method of the instant claim.
Claims 1-10 and 12-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kaiser et al (US 2017/0037370 A1) as evidenced by Jakubzick et al (Nature Reviews Immunology, 2017), in view of Masquelier et al (US 2019/0002814 A1, of record on IDS filed 13 March 2025), and further in view of Sadelain et al (US 2021/0236554 A1).
The discussion of Kaiser et al as modified by Masquelier et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Kaiser et al as evidenced by Jakubzick et al and as modified by Masquelier et al render obvious claims 1-10, 12-13, and 18-19. Sadelain et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 19 October 2018.
Regarding claims 14-15: As aforementioned in the discussion of claim 1 above, Kaiser et al disclose that the CAR comprises an extracellular antigen binding domain. Kaiser et al further disclose that extracellular domain of the CAR comprises a signal peptide, an antigen binding domain, and a spacer (Paragraphs [0103]-[105], [0108]-[109]). Kaiser et al further disclose an anti-CD20 CAR (Paragraphs [0058], [0061], [0115]).
Kaiser et al further disclose that the harvested CAR T cells can be utilized as a therapeutic (Paragraphs [0002], [0110]-[0113]).
The combination of Kaiser et al and Masquelier et al fail to teach that the signal peptide is a scFv, as required by instant claim 14.
Sadelain et al, however, disclose therapeutic CAR T cells having an extracellular domain comprising an scFv, which is a fusion protein of the light and heavy chains of immunoglobulins that are fused by a flexible linker (Abstract; Paragraphs [0005], [0053], [0055], [0057], [0070], [0092], [0110], [0115]-[0117], [0213], [0227]-[0229]). Sadelain et al further disclose that the CAR can be an anti-CD20 CAR (Paragraphs [0011], [0096]).
Therefore, it would have been prima facie obvious to have substituted the extracellular signal peptide within the CAR of Kaiser et al with the scFv of Sadelain et al, as doing so would have been a simple substitution of one CAR signal peptide for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two extracellular signal peptides are functionally comparable, as both are comprised within anti-CD20 CARs, and thereby would have been able to substitute the two signal peptides with predictable results.
Consequently, Kaiser et al as modified by Masquelier et al and Sadelain et al render obvious a method of automatically editing a T cell culture to express a CAR, wherein the CAR comprises an extracellular domain including a scFv signal peptide (claim 14). As the scFv is a fusion protein of the light and heavy chains of immunoglobulins that are fused by a flexible linker, this therefore renders obvious the method of instant claim 15.
Regarding claim 16: As aforementioned in the discussion of claim 1 above, Kaiser et al disclose that the CAR comprises a transmembrane domain. Kaiser et al further disclose an anti-CD20 CAR (Paragraphs [0058], [0061], [0115]).
Kaiser et al further disclose that the harvested CAR T cells can be utilized as a therapeutic (Paragraphs [0002], [0110]-[0113]).
The combination of Kaiser et al and Masquelier et al fail to teach that the transmembrane domain is a hydrophobic α-helix that spans a membrane, as required by instant claim 16.
Sadelain et al, however, disclose therapeutic CAR T cells having a transmembrane domain comprising a hydrophobic alpha helix that spans at least a portion of the membrane (Abstract; Paragraphs [0005], [0012], [0057], [0070], [0092], [0110], [0113], [0128]-[0142], [0213], [0227]-[0229]). Sadelain et al further disclose that the CAR can be an anti-CD20 CAR (Paragraphs [0011], [0096]).
Therefore, it would have been prima facie obvious to have substituted the transmembrane domain within the CAR of Kaiser et al with the transmembrane domain of Sadelain et al, as doing so would have been a simple substitution of one CAR transmembrane domain for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two transmembrane domains are functionally comparable, as both are comprised within anti-CD20 CARs, and thereby would have been able to substitute the two transmembrane domains with predictable results.
Consequently, Kaiser et al as modified by Masquelier et al and Sadelain et al render obvious a method of automatically editing a T cell culture to express a CAR, wherein the CAR comprises a transmembrane domain comprising a hydrophobic α-helix that spans a membrane. This therefore renders obvious the method of the instant claim.
Regarding claim 17: As aforementioned in the discussion of claim 1 above, Kaiser et al disclose that the CAR comprises an intracellular signaling domain. Kaiser et al further disclose an anti-CD20 CAR (Paragraphs [0058], [0061], [0115]).
Kaiser et al further disclose that the harvested CAR T cells can be utilized as a therapeutic (Paragraphs [0002], [0110]-[0113]).
The combination of Kaiser et al and Masquelier et al fail to teach that the intracellular signaling domain is a CD3ζ intracellular signaling domain comprising 3 ITAMs, as required by instant claim 17.
Sadelain et al, however, disclose therapeutic CAR T cells having an intracellular signaling domain comprising a CD3ζ polypeptide, which comprises 3 ITAMs (Abstract; Paragraphs [0005], [0050], [0057], [0070], [0092], [0110], [0144]-[0150], [0213], [0227]-[0229]). Sadelain et al further disclose that the CAR can be an anti-CD20 CAR (Paragraphs [0011], [0096]).
Therefore, it would have been prima facie obvious to have substituted the intracellular signaling domain within the CAR of Kaiser et al with the CD3ζ intracellular signaling domain of Sadelain et al, as doing so would have been a simple substitution of one CAR intracellular signaling domain for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two intracellular signaling domains are functionally comparable, as both are comprised within anti-CD20 CARs, and thereby would have been able to substitute the two intracellular signaling domains with predictable results.
Consequently, Kaiser et al as modified by Masquelier et al and Sadelain et al render obvious a method of automatically editing a T cell culture to express a CAR, wherein the CAR comprises a CD3ζ intracellular signaling domain including 3 ITAMs. This therefore renders obvious the method of the instant claim.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-22 of U.S. Patent No. 12163146 B2 in view of Kaiser et al (US 2017/0037370 A1) and Sadelain et al (US 2021/0236554 A1). It is of note that the instant application is a CONTINUATION of U.S. Patent No. 12163146 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims render obvious the instant claims. More specifically, the patent claims are not identical because no single patent claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patented claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a method for assessing and optimizing cellular quality of a chimeric antigen receptor T (CAR T) cell culture, comprising:
(a) determining one or more molecular characteristics of a pre-modified T-cell culture;
(b) optimizing one or more parameters of an automated cell engineering system to alter the one or more molecular characteristics of the pre-modified T-cell culture;
(c) activating the pre-modified T-cell culture with an activation reagent to produce an activated T-cell culture;
(d) transducing the activated T-cell culture with a vector encoding a chimeric antigen receptor, to produce a CAR T-cell culture;
(e) expanding the CAR T-cell culture;
(f) concentrating the expanded CAR T-cell culture of (e);
(g) harvesting the concentrated CAR-T cell culture of (f);
(h) automatically determining via the automated cell engineering system the one or more molecular characteristics of the CAR T-cell culture during or after any one of steps (c)-(g); and
(i) automatically optimizing one or more parameters of any one of steps (c)-(g) to alter the one or more molecular characteristics of the CAR T-cell culture based on the automatically determined one or more molecular characteristics, wherein the optimizing includes one or more of increasing or decreasing a flow rate of cell media, increasing or decreasing oxygen concentration, increasing or decreasing carbon dioxide concentration, increasing or decreasing a glucose level, increasing or decreasing a pH of cell media, and/or modifying a selection reagent used in a cell isolation procedure.
Patent claim 1 does not disclose that the CAR comprises an ectodomain, transmembrane domain, and endodomain, as required by instant claim 1.
Kaiser et al, however, disclose an automatic process for the generation of genetically modified T cells that is performed in a closed and sterile cell culture system, wherein the T cells may be genetically modified to express a chimeric antigen receptor (CAR) on their cell surface (Abstract; Paragraphs [0037], [0070]-[0071], [0108]-[0109]). Kaiser et al further disclose that the CAR comprises an extracellular domain, a transmembrane domain, and at least one intracellular signaling domain (Paragraph [0108]).
Therefore, it would have been prima facie obvious to have substituted the CAR of the patent claims with the CAR of Kaiser et al, as doing so would have been a simple substitution of one CAR utilized within an automated culture process for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two CARs are functionally comparable, as both are automatically transduced into T cells, and thereby would have been able to substitute the two CARs with predictable results.
Consequently, patent claim 1 as modified by Kaiser et al renders obvious the method of instant claim 1.
With that, instant claims 2-19 are known from the patent or prior art and can be further incorporated into the method rendered obvious to patent claim 1 as modified by Kaiser et al:
Patent claims 12-22 teach the limitations recited in instant claims 2-12.
Kaiser et al teach the limitations recited in instant claims 13 and 18-19.
Sadelain et al teach the limitations recited in instant claims 14-17.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
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