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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 26th of August 2025 has been entered.
Priority
This application was filed 18th of June 2019 and is a 371 application of PCT/GB2017/053835 filed on 20th of December 2017, which claims benefit to the foreign application GB1621891.9 filed on 21st of December 2016.
Status of the Application
Applicant’s response and amendment filed 26th of August 2025 are acknowledged and entered.
Applicant’s election of the species in which the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline (i.e. Group 13) in the reply filed on 22nd of May 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)).
Claim Status
In the reply filed 26th of August 2025, Applicants have amended claims 23, 28, and 31, and canceled claims 1-22, 24, 26-27, 29-30, 32, 36, 39-42, 45, 48 and 50. Currently, claims 23,25, 28,31, 33-35, 37-38,43-44 46-47 and 49 are pending.
However, claims 35, 38, 43-44, and 46-47 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Currently, claims 23, 25, 28, 31, 33-34, 37, and 49 are under consideration.
Information Disclosure Statement
Applicant is reminded of 37 CFR §1.56, which details Applicant's duty to disclose all information known to be material to patentability.
If the disclosure statements filed lists a “Search Reports”. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a). Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The rejection of claims 23, 25, 28, 31, 33-34, 49 and 50 under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al. (WO 2016138034 A1, published 2016, previously cited) is withdrawn due to Applicants amendments to the claims of the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline.
The rejection of claim is 23 and 37 under 35 U.S.C. 103 as being unpatentable over Lim et al. (WO 2016138034 A1, published 2016, previously cited) and He, et al., (Proceedings of the National Academy of Sciences 114.21: 5467-5472, published 2017, previously cited), and Stassinopoulos et al. (WO2016073381A1, published 2016, previously cited) is withdrawn due to Applicants amendments to the claims of the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline.
Improper Markush
This rejection is a new rejection necessitated by amendments to the claims.
Claims 23, 28, and 31 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the first and second binding domain and agent, wherein:
(1) the first binding domain is p53, the second binding domain is MDM2, and the agent is nutin, (2) the first binding domain is MDM2, the second binding domain is p53, and the agent is nutin, (3) the first binding domain is anti-apoptotic Bcl2 member, the second binding domain is apoptotic Bcl2 member, and the agent is GX015 or ABT-737, (4) the first binding domain is apoptotic Bcl2 member, the second binding domain is anti-apoptotic Bcl2 member, and the agent is is GX015 or ABT-737, (5) the first binding domain is caspase-3, caspase-7 or caspase-9, the second binding domain is X-lined inhibitory of apoptosis protein (XIAP), and the agent is DIABLO or a DIABLO mimetic, (6) the first binding domain is X-linked inhibitory of apoptosis protein (XIAP), The second binding domain is caspase-3, caspase-7 or caspase-9, and the agent is DIABLO or a DIABLO mimetic, (7) the first binding domain is RAS, the second binding domain is RAF. and the agent is a furano-indene derivative, (8) the first binding domain is RAF. the second binding domain is RAS. and the agent is a furano-indene derivative (9) the first binding domain is FR2-7. the second binding domain is the PD2 domain of DVL, and the agent is FJ9, (10) the first binding domain is the PD2 domain of DVL. the second binding domain is FR2-7. and the agent is FJ9, (11) the first binding domain is T-cell factor. the second binding domain is cyclic AMP response element binding protein, and the agent is ICG-001, (12) the first binding domain is cyclic AMP response element binding protein, The second binding domain is T-cell factor. and the agent is ICG-001, (13) the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline, (14) the first binding domain is TIP, the second binding domain is TetR, and the agent is tetracycline, Doxycycline, or minocycline, (15) the first binding domain is a streptavidin-binding epitope, the second binding domain is a biotin mimic and the agent is biotin, or (16) the first binding domain is a biotin mimic, the second binding domain is a streptavidin-binding epitope, and the agent is biotin
is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The alternatives are not part of the same art-recognized class and are not considered to be functionally equivalent, for example: the first binding domain is caspase-3, and the first binding domain is a streptavidin-binding epitope, are different binding domains. Thus, the alternatives fail to share a single structure or functional similarity (i.e. enzyme versus antigen). Further, the first and second binding domains have different agents (i.e. DIABLO versus biotin), which results in different outcomes (i.e. functions of the binding domains).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 23, 25, 28, 31, 33-34, 37, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Pule et al. (WO2016/030691A1, published March 2016; hereinafter as “Pule 2016”, cited IDS 9/19/2019), Bujard, Hermann (WO96/01313, published 1996; hereinafter as “Bujard”), Klotzsche et al., (J. Biol. Chem. 280:24591-9, published 2005, hereinafter “Klotzsche” cited IDS 9/19/2019), and Luckner, Sylvia R., et al. (Journal of molecular biology 368.3: 780-790, published 2007; hereinafter as “Luckner,” cited IDS 9/19/2019).
This rejection is a new rejection necessitated by amendments to the claims.
Regarding claim 23, 28, 31, 33-34, and 49, Pule 2016 discloses a vector encoding a transcription system which comprises (a) a first nucleic acid sequence encoding a docking component which comprises a first binding domain (i.e. TetR) and a membrane localization domain (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4, 32, and pages 7-9, 27-40), wherein the membrane localization domain comprises a transmembrane sequence, a stop transfer sequence (i.e. a CD4 derived transmembrane and intracellular domain) (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4). Further, Pule 2016 discloses (b) a second nucleic acid sequence encoding a second binding domain which binds the first binding domain of the docking component (e.g. CAR with TetR)(see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4); Further, Pule 2016 discloses wherein binding of the first and second binding domains is competitively disrupted by the presence of an agent (e.g. tetracycline)(see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4); such that in the absence of the agent, the docking components heterodimerize and are held on the intracellular side of the plasma membrane (see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4). Further, Pule 2016 discloses whereas the presence of the agent competitively dissociates the transcription control component from the docking component by the agent competitively binding to the docking component (see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4), and wherein: (13) the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline (see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4).
Pule 2016 does not explicitly disclose the second nucleic acid sequence encoding a transcription control component, which comprises a transcription factor, a nuclear localization signal, and where the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene.
However, the prior art of Bujard discloses a Tet repressor fusion protein comprising a transcription control component (e.g. VP16), which comprises a transcription factor (e.g. Gal4), a nuclear localization signal (e.g. NLS) (see e.g. pages 3, 14-15, 30, 36, 52, 57, 61, 65). Further, the Specification discloses the prior art of Klotzsche and Luckner for controlling the co-localization of peptides are known in the art and the control component being TetR or TiP (see Spec. para. 242-245).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the transcriptional system, as taught by Pule 2016, and incorporate a transcription control component, which comprises a transcription factor and a nuclear localization signal, as taught by Bujard, Klotzsche and Luckner, with a reasonable expectation of success because one of ordinary skill in the art would know that controlling the co-localization of peptides are known in the art and the control component may be fused with the TetR or TiP (see Spec. para. 242-245). Further, a person of ordinary skill in the art would know that a Tet repressor fusion protein may comprise a transcription control component, which comprises a transcription factor and a nuclear localization signal (as taught by Bujard, as discussed above).
As stated above, Pule 2016 et al. does not explicitly disclose the second nucleic acid sequence encoding a transcription control component, which comprises a transcription factor, a nuclear localization signal, and where the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene.
Nevertheless, the outcomes of the transcription system in the presence or absence of the agent is considered to necessarily flow from the teachings of Pule 2016, Bujard, Klotzsche and Luckner, since Pule 2016 teaches the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline (see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4), as discussed above. Thus, the outcome of the presence or absence of the agent must therefore flow from the same structure as taught by Pule 2016 and will naturally have the same effect.
Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims."
Regarding the issue of inherency, see Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). (see MPEP 2112 (IV)).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the effective filing date to modify the vector encoding transcription system as taught by Pule 2016 with a reasonable expectation of success because a person of ordinary skill in the art would have done so because the transcription system of Pule 2016 discloses that a signal peptide may be incorporated to help enforce proper topology of the polypeptide during translocation (see e.g. page 20). Further, Pule 2016 discloses that the transcription system allows the potency of CAR cells to be controlled pharmacologically and tuned to an acceptable balance between achieving the desired therapeutic effect and avoiding unwanted toxicities (see e.g. page 9). Thus, providing motivation to do.
Regarding claim 25, as stated supra, Pule 2016 discloses a third nucleic acid sequence encoding a chimeric antigen receptor (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4 and page 35).
Regarding claim 33, as stated supra, Pule 2016 discloses a cell which comprises a vector (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4 and pages 1-9, 10, 27-31, 35, 39).
Regarding claim 34, as stated supra, Pule 2016 discloses a cell which expresses a chimeric antigen receptor (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4 and pages 1-10, 27-31, 33-35, 39).
Regarding claim 37, as stated supra, Pule 2016 discloses a pharmaceutical composition comprising a plurality of cells (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4 and pages 1-9, 33-35, 39-40).
Regarding claim 49, as stated supra, Pule 2016 discloses a composition which comprises a plurality of cells with the agent which disrupts binding of the first and second binding domains (see e.g. abstract, examples 1-3, fig. 1-12, claims 1-4 and pages 22, 28, 35 and 38-40).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 23, 25, 28, 31, 33-34, 37, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Pule et al. (WO2015150771A1, published Oct. 8, 2015, hereinafter as “Pule 2015”; cited IDS 9/19/2019), Wu et al., (WO2014/127261A1, published 2014), Bujard, Hermann (WO96/01313, published 1996; hereinafter as “Bujard”), Klotzsche et al., (J. Biol. Chem. 280:24591-9, published 2005, hereinafter “Klotzsche” cited IDS 9/19/2019), and Luckner, Sylvia R., et al. (Journal of molecular biology 368.3: 780-790, published 2007; hereinafter as “Luckner,” cited IDS 9/19/2019).
This rejection is a new rejection necessitated by amendments to the claims.
Regarding claims 23, 28, 31, 33-34, and 49, Pule 2015 discloses a vector encoding a transcription system (see e.g. abstract and page 30-34), which comprises (a) a first nucleic acid sequence encoding a docking component which comprises a first binding domain and a membrane localization domain, wherein the membrane localization domain comprises a transmembrane sequence (see e.g. abstract, Examples 1-3, and fig. 1-11, claims 1-23); (b) a second nucleic acid sequence encoding a second binding domain which binds the first binding domain of the docking component (see e.g. abstract, Examples 1-3, and fig. 1-11, claims 1-23).
Pule 2015 does not explicitly disclose that the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), the agent is tetracycline, and wherein binding of the first and second binding domains is competitively disrupted by the presence of an agent (i.e. CID), such that in the absence of the agent, the docking component and the transcription control component heterodimerize and the transcription control component is held on the intracellular side of the plasma membrane; whereas the presence of the agent competitively dissociates the transcription control component from the docking component by the agent competitively binding to the docking component and the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene.
Nevertheless, Pule 2015 discloses the same principle of a protein complex with which signaling occurs through a signaling component and a receptor component interacting via binding domains which necessitate a small molecule (i.e. agent). However, the system of Pule is always turned on and the continuous activity of the CAR is known to be toxic. Thus, a person of ordinary skill in the art would want to avoid toxicity, and said CAR would be better in an inactivated state first and then the activity turned on as needed (i.e. in the presence of an agent).
Furthermore, Pule 2015 discloses that the system may be used to avoid toxicity by reciting that “another possibility of this system is to "tune" the signal strength the receptor transmits. If the affinity between one or both of the CID binding domains is lessened, less CAR systems will be active and hence signal propagation upon antigen binding is lessened”(see e.g. page 13). Further, the prior art of Wu discloses the use of CARs with reversible inducible promoters, such as tetracycline regulated promoters, (e.g., promoter systems including Tet Activators, TetON, TetOFF, etc.)(see e.g. abstract, para. 197). Additionally, the prior art of Bujard disclose that it was well known that the binding of tetracycline (referred to as reverse tetracycline controlled transactivator)(i.e. tSD) to the tetO sequences in the absence of tetracycline or analogue ( e.g. doxycycline) inhibits the basal constitutive transcription of the gene of interest, thus keeping the gene of interest in a repressed state until gene expression is desired (see e.g. abstract, and page 43).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the transcriptional system, as taught by Pule 2015, and incorporate a reverse tetracycline controlled transactivator system as taught by Wu and Bujard, with a reasonable expectation of success because one of ordinary skill in the art would know that controlling the transcriptional system as suggested by Pule 2015 would avoid toxicity (as suggested by Pule 2015, and Bujard, as discussed above).
As stated above, Pule 2015 et al. does not explicitly disclose the second nucleic acid sequence encoding a transcription control component, which comprises a transcription factor, a nuclear localization signal, and where the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene.
However, the prior art of Bujard discloses a Tet repressor fusion protein comprising a transcription control component (e.g. VP16), which comprises a transcription factor (e.g. Gal4), a nuclear localization signal (e.g. NLS) (see e.g. pages 3, 14-15, 30, 36, 52, 57, 61, 65). Further, the Specification discloses the prior art of Klotzsche and Luckner for controlling the co-localization of peptides are known in the art and the control component being TetR or TiP (see Spec. para. 242-245).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have combined the transcriptional system, as taught by Pule 2015, and incorporate a transcription control component, which comprises a transcription factor and a nuclear localization signal, as taught by Bujard, Klotzsche and Luckner, with a reasonable expectation of success because one of ordinary skill in the art would know that controlling the co-localization of peptides are known in the art and the control component may be fused with the TetR or TiP (see Spec. para. 242-245). Further, a person of ordinary skill in the art would know that a Tet repressor fusion protein may comprise a transcription control component, which comprises a transcription factor and a nuclear localization signal (as taught by Bujard, as discussed above).
As stated above, Pule 2015 et al. does not explicitly disclose the second nucleic acid sequence encoding a transcription control component, which comprises a transcription factor, a nuclear localization signal, and where the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene.
Nevertheless, the outcomes of the transcription system in the presence of absence of the agent is considered to necessarily flow from the teachings of Pule 2015, Bujard, Klotzsche and Luckner, since Pule 2015 teaches the first binding domain is TetR, the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline, doxycycline, or minocycline (see e.g. abstract, examples 1-3, fig. 1-12, and claims 1-4), as discussed above. Thus, the outcome of the presence or absence of the agent must therefore flow from the same structure as taught by Pule 2015 et al., and will naturally have the same effect.
Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims."
Regarding the issue of inherency, see Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). (see MPEP 2112 (IV)).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the effective filing date to modify the vector encoding transcription system as taught by Pule 2015 with a reasonable expectation of success because a person of ordinary skill in the art would have done so because the transcription system of Pule 2015 discloses that a signal peptide may be incorporated to help enforce proper topology of the polypeptide during translocation (see e.g. page 20). Further, Pule 2015 discloses that the transcription system allows the potency of CAR cells to be controlled pharmacologically and tuned to an acceptable balance between achieving the desired therapeutic effect and avoiding unwanted toxicities (see e.g. page 2-139). Thus, providing motivation to do.
Regarding claim 25, Pule 2015 discloses a third (i.e. plurality) nucleic acid sequence encoding a chimeric antigen receptor (see e.g. abstract, Examples 1-3, and fig. 1-11, claims 1-23, and pages 4, 26, 28, 33-36, and 54).
Regarding claim 37, Pule 2015 a pharmaceutical composition comprising a plurality of cells (see e.g. abstract, Examples 1-3, and fig. 1-11, claims 1-23, and pages 4, 26, 28, 33-36, 54).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
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 23, 25, 28, 31, 33-34, 37, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, and 15 of U.S. Patent No. US10654927 B2 (published 2020; hereinafter as “the ’927 patent”) in view of Pule et al., (WO2016030691A1, published March 2016, cited IDS 9/19/2019).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the competing claims are drawn to a disclosed species of the instant claims.
The instant claims are directed to:
A vector encoding a transcription system which comprises (a) a first nucleic acid sequence encoding a docking component which comprises a first binding domain and a membrane localization domain, wherein the membrane localization domain comprises a transmembrane sequence, a stop transfer sequence, a GPI anchor or a myristoylation/prenylation/palmitoylation site; and (b) a second nucleic acid sequence encoding a transcription control component which comprises a transcription factor, a nuclear localization signal and a second binding domain which binds the first binding domain of the docking component; wherein binding of the first and second binding domains is competitively disrupted by the presence of an agent, such that in the absence of the agent, the docking component and the transcription control component heterodimerize and the transcription control component is held on the intracellular side of the plasma membrane; whereas the presence of the agent competitively dissociates the transcription control component from the docking component by the agent competitively binding to the docking component and the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene: and wherein (13) the first binding domain is TetR. the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline. doxycycline. or minocycline (see claim 23).
The ‘927 patent’s claims are directed to:
“A chimeric antigen receptor (CAR) system comprising; (i) a receptor component comprising an extracellular antigen binding domain, a spacer, a transmembrane domain, and a first intracellular binding domain; and (ii) an intracellular signaling component comprising a signaling domain and a second binding domain which specifically binds to the first intracellular binding domain of the receptor component; wherein (i) and (ii) are separate molecules; wherein the receptor component and signaling component are co-expressed; wherein binding of the first and second binding domains of the CAR system is disruptable by the presence of an agent, wherein, in the absence of the agent, the receptor component and the intracellular signaling component heterodimerize, and binding of the antigen binding domain to antigen results in signaling through the signaling domain, whereas in the presence of the agent, the receptor component and the signaling component do not heterodimerize, and binding of the antigen binding domain to antigen does not result in signaling through the signaling domain; and wherein the first intracellular binding domain comprises Tet Repressor Protein (TetR) or a variant thereof and the second binding domain comprises Transcription inducing peptide (TiP) or a variant thereof; or wherein the first intracellular binding domain comprises TiP or a variant thereof and the second binding domain comprises TetR or a variant thereof; and the agent is tetracycline, doxycycline or minocycline or an analogue thereof” (see claims 1-16).
Both claims are direct to a receptor component and signaling component that are co-expressed in a system, wherein binding of the first and second binding domains of the system is disruptable by the presence of an agent. Further, both claims are directed to the first intracellular binding domain comprises Tet Repressor Protein (TetR) or a variant thereof and the second binding domain comprises Transcription inducing peptide (TiP) or a variant thereof; or wherein the first intracellular binding domain comprises TiP or a variant thereof and the second binding domain comprises TetR or a variant thereof; and the agent is tetracycline, doxycycline or minocycline or an analogue thereof.
The patented claims do not recite a kit of nucleic acid sequence vectors encoding a transcription system.
However, the kit of nucleic acid sequence vectors encoding a transcription system would have been obvious in view of the prior art in view of Pule et al.(see e.g. col. 6, and 19-21)
It would have been obvious for one of ordinary skill in the art to use the patented claims and modify it with a kit of nucleic acid sequence vectors encoding a transcription system, as taught by Pule et al.(see e.g. col. 6, and 19-21), for the benefit of optimizing therapy that would provide acceptable monitoring of disease progression (as taught by Pule et al., see e.g. col. 6). One would have been motivated to do so with a reasonable expectation of success because the cited prior art teaches the benefits of making those modifications.
Therefore, all the limitations of the instant claims would have been obvious in view of the patented claims an ‘927 patent’s claims and the cited prior art.
Claims 23, 25, 28, 31, 33-34, 37, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. US12187769 B2 (published 2025; hereinafter as “the ’769 patent”) in view of Pule et al., (WO2016030691A1, published March 2016, cited IDS 9/19/2019).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the competing claims are drawn to a disclosed species of the instant claims.
The instant claims are directed to:
A vector encoding a transcription system which comprises (a) a first nucleic acid sequence encoding a docking component which comprises a first binding domain and a membrane localization domain, wherein the membrane localization domain comprises a transmembrane sequence, a stop transfer sequence, a GPI anchor or a myristoylation/prenylation/palmitoylation site; and (b) a second nucleic acid sequence encoding a transcription control component which comprises a transcription factor, a nuclear localization signal and a second binding domain which binds the first binding domain of the docking component; wherein binding of the first and second binding domains is competitively disrupted by the presence of an agent, such that in the absence of the agent, the docking component and the transcription control component heterodimerize and the transcription control component is held on the intracellular side of the plasma membrane; whereas the presence of the agent competitively dissociates the transcription control component from the docking component by the agent competitively binding to the docking component and the transcription control component translocates to the nucleus where the transcription factor of the transcription control component binds DNA and regulates the transcription of a gene: and wherein (13) the first binding domain is TetR. the second binding domain is TetR interacting protein (TIP), and the agent is tetracycline. doxycycline. or minocycline (see claim 23).
The ‘769 patent’s claims are directed to:
A cytolytic immune cell which comprises a CAR and an inducible Signal Transducer and Activator of Transcription (STAT) molecule, wherein (a) the STAT molecule comprises a first polypeptide comprising a first dimerizing domain (DD) and a second polypeptide comprising a second DD, which second DD specifically binds to the first DD; and wherein the presence of an agent causes dimerization of the first and second DD and induces activation of the STAT molecule, or (b) the STAT molecule comprises a first polypeptide comprising a first dimerizing domain (DD) and a second polypeptide comprising a second DD, which second DD specifically binds to the first DD; and wherein the presence of an agent causes dissociation of the first and second DD and induces non-activation of the STAT molecule (see claim1). A cell according to claim 1 (a), wherein the first DD comprises FRB and the second DD comprises FKBP12 and the agent is rapamycin (see claim 2). A cell according to claim 1 (b), wherein the first DD comprises Tet Repressor Protein (TetR) and the second DD comprises Transcription Inducing Peptide (TiP); and the agent is tetracycline, doxycycline or minocycline (see claims 1-3).
Both claims are direct to a receptor component and signaling component that are co-expressed in a system, wherein binding of the first and second binding domains of the system is disruptable by the presence of an agent. Further, both claims are directed to the first intracellular binding domain comprises Tet Repressor Protein (TetR) or a variant thereof and the second binding domain comprises Transcription inducing peptide (TiP) or a variant thereof; or wherein the first intracellular binding domain comprises TiP or a variant thereof and the second binding domain comprises TetR or a variant thereof; and the agent is tetracycline, doxycycline or minocycline or an analogue thereof.
The patented claims do not recite a vector or a kit of nucleic acid sequence vectors encoding a transcription system.
However, the vector and kit of nucleic acid sequence vectors encoding a transcription system would have been obvious in view of the prior art in view of Pule et al.(see e.g. col. 6, and 19-22)
It would have been obvious for one of ordinary skill in the art to use the patented claims and modify it with a vector or kit of nucleic acid sequence vectors encoding a transcription system, as taught by Pule et al.(see e.g. col. 6, and 19-21), for the benefit of optimizing therapy that would provide acceptable monitoring of disease progression (as taught by Pule et al., see e.g. col. 6). One would have been motivated to do so with a reasonable expectation of success because the cited prior art teaches the benefits of making those modifications.
Therefore, all the limitations of the instant claims would have been obvious in view of the patented claims an ‘769 patent’s claims and the cited prior art.
Conclusion
No claim is allowed.
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Josephine Gonzales PhD
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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