DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of the species of CD90 in the reply filed on 04/13/2026 is acknowledged. The traversal is on the ground(s) that the claim requires at least two antigen recognizing moieties and not a single species election. This is found persuasive and the election requirement is withdrawn.
Status of the Claims
Claims 1-15 are currently pending.
Claims 1-15 are amended.
Claims 1-15 have been considered on the merits.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-21 of copending Application No. 16/823,012 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a process for providing CAR cells comprising steps of screening tumor antigens as described below.
Instant claim 1 falls entirely within the scope of claim 13 of ‘012. Instant claim 1 requires the active steps of “contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety” which is met by step (b) of claim 13 of ‘012; “removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates” which is met by steps (c)-(d) of claim 13 of ‘012; and “erasing the fluorescence emitted by the fluorescent moieties of the conjugates” which is met by step (e) of claim 13 of ‘012. Dependent claim 2 is met by independent claim 13 of ‘012. Dependent claim 3 is met by claim 14 of ‘012. Dependent claim 4 is met by claim 15 of ‘012. Dependent claim 5 is met by claims 16 and 17 of ‘012. Dependent claim 6 is met by claims 16 and 17 of ‘012. Dependent claim 7 is met by claim 18 of ‘012. Dependent claim 8 is met by claim 19 of ‘012. Dependent claim 10 is met by claim 13 of ‘012. Dependent claim 15 is met by claim 13 of ‘012. Claims 9 and 11-14 describe specific erasure techniques or targeting antigens while the claims of ‘012 do not, however both sets of the claims are drawn to the same method of screening for CAR with fluorescent labelled antibody conjugates and both sets of claims have the same steps to obtains CAR cells, thus the claims of ‘012 recite a species of the presently claimed genus and the claims of ‘012 would anticipate and render obvious the presently claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Objections
Claim 7 is objected to because of the following informalities: “at least at least 20%” is a duplicate in line 3. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “binding” in line 3 should be amended to “bind”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: “chimeric antigen receptor (CAR)” should be amended to “a chimeric antigen receptor (CAR)”. Additionally, “a cell comprising biotin as antigen” should be amended to “a cell comprising biotin as an antigen”. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: “chimeric antigen receptor (CAR)” should be amended to “a chimeric antigen receptor (CAR)”. Additionally, “a cell comprising biotin as antigen” should be amended to “a cell comprising biotin as an antigen”. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: the phrase “is erased by enzymatically degrading of the conjugates” is grammatically incorrect and should be amended to “is erased by degrading the conjugates enzymatically” or similar. Appropriate correction is required.
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 1-15 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.
Claim 1 recites the phrase “and repeating the steps of” in line 4 of claim 1, which is indefinite. It is not clear if Applicant intends to limit the claim to requiring a repetition of the steps of “contacting”, “removing”, and “erasing”. It is not clear if repetition is required if the first round of completing the steps positively identifies two conjugates of antigen recognizing moieties. Appropriate clarification is required. Dependent claims 2-15 are included in this rejection due to dependency on claim 1.
Claim 1 recites the limitation "the cell tissue" in lines 5 and 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the first conjugates" in lines 8-9. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the fluorescence radiation" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the phrase “allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells”, which is indefinite. It is unclear what the phrase imparts on the claim and how the claimed steps achieve this result. Appropriate clarification is required.
Claim 1 recites the limitation "the identified at least two antigen recognizing moieties" in the last two lines. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites “of the conjugates” in line 10. It is unclear which conjugates applicant is referring to because “a conjugate” is introduced in line 5, “unbound conjugate” is introduced in line 7, “the first conjugates” is introduced in lines 8-9. Thus, it is not clear to which conjugates Applicant is referring to in line 10.
Claim 2 recites the limitation "the cell comprising a chimeric antigen receptor" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 5 and 6 generally recite providing a cell comprising biotin as an antigen recognizing moiety of a CAR and providing conjugates of the identifies at least two antigen recognizing moieties with an anti-biotin moiety, which is unclear. It is not clear if the claimed CAR is meant to be a receptor for the at least two antigen recognizing moieties or to be a biotin receptor, further it is not clear if the at least two antigen recognizing moieties are meant to be conjugated with an anti-biotin moiety, the CAR, or both. Appropriate clarification is required.
Claim 12 recites the limitation "tumor stromal cells" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation "PaCa cells" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the phrase “allowing in combination to discriminate between tumor microenvironment cells and tumor cells against non-tumor microenvironment cell”, which is indefinite. It is unclear what the phrase imparts on the claim and how the claimed steps achieve this result. Appropriate clarification 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.
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 1-2, 5-10, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Bosio et al (EP3311832 A1), in view of Dose et al (EP3037821B1).
Regarding claim 1, Bosio teaches a method of making, identifying and preparing cells engineered to express a CAR containing an antigen binding domain specific to one or more antigens exposed on the tumor microenvironment cells (abstract, Claim 1, and [0087]). Bosio teaches that “The treatment of cancer may encompass any method which involves at least one antigen as disclosed or any combination of antigens as disclosed as target molecule” ([0087]). Additionally, Example 15 details that cells expressing one or more pancreas cancer specific targets were incubated with T cells expressing pancreas cancer specific CARs and T cells containing the CAR were the only cells able to kill the target cancer cells ([0111]).
Regarding claim 2, Bosio teaches that the cell comprising the CAR is selected from a T cell, NK cell, or a cell engineered to destroy other cells when triggered by the binding of the other cell ([0028]).
Regarding claims 5 and 6, Bosio teaches that the cells provided with the at least two antigen recognizing moieties as chimeric antigen receptors by providing an anti-tag binding region which can bind to a tag which is coupled to an antigen binding domain ([0035]). Further, Bosio teaches that the tag is biotin ([0035]).
Regarding claims 7 and 8, both claims contain a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. The intended result of the method appears to be selecting conjugates that “the at least two conjugates provided with antigen recognizing moieties binding at least at least 25% of the tumor microenvironment and less than 5 % of the non-tumor microenvironment cells” of claim 7 and “the at least two conjugates provided with antigen recognizing moieties binding at least 10-fold more tumor microenvironment cells than non-tumor microenvironment cells of the cell sample” of claim 8. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since these claims only recite the results of the steps, then art reading on claim 1 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Regarding claim 10, Bosio teaches that the cells comprising a CAR specific to one or more target antigens exposed on pancreatic tumor microenvironment are further specific to the pancreatic cancer cells of that specific environment as demonstrated in Example 15 ([0111]-[0112]).
Regarding claim 15, Bosio teaches a method of making, identifying and preparing cells engineered to express a CAR containing an antigen binding domain specific to one or more antigens exposed on the tumor microenvironment cells (abstract, Claim 1, and [0087]). Bosio teaches that “The treatment of cancer may encompass any method which involves at least one antigen as disclosed or any combination of antigens as disclosed as target molecule” ([0087]). Additionally, Example 15 details that cells expressing one or more pancreas cancer specific targets were incubated with T cells expressing pancreas cancer specific CARs and T cells containing the CAR were the only cells able to kill the target cancer cells ([0111]).
Bosio does not teach that the specific antigen recognizing moieties of the CAR molecule are chosen through the process steps of contacting, removing, and erasing as required by claim 1. Bosio does not teach that the fluorescence radiation emitted by the fluorescent moieties is erased by enzymatically degrading of the conjugates as required by claim 9.
Does teaches a process for providing a cell with a CAR specific to one or more target antigens exposed on any biological specimen including tissues, organs, cell aggregates, and suspension or adherent cells ([0022]) by repeating the steps of:
Contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety ([0019]/[0023])
Removing unbound conjugate from the cell tissue ([0021]) and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates ([0024]/See claim 1)
Erasing the fluorescence emitted by the fluorescent moieties of the conjugates (See claim 1/[0065]).
Additionally, Dose teaches performing the method until identifying at least two conjugates wherein each antigen recognizing moiety recognizes different antigens (See claim 1). Further, Does teaches simultaneous labelling of cells with three antigen recognizing moieties to achieve discrimination of different cell subpopulations using fluorescence prior to the erasing step of the instant claim ([0085]/[0086]).
Regarding claim 9, Dose teaches that the erasing step is performed by enzymatically degrading the conjugates (See claim 1 and [0001]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the CAR immune cell of Bosio with the process steps of identifying antigen recognizing moieties towards a target tissue taught by Dose to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Dose teaches simultaneous labelling of cells with three antigen recognizing moieties to achieve discrimination of different cell subpopulations using fluorescence prior to the erasing step of the instant claim ([0085]/[0086]) and Bosio teaches choosing pancreas cancer specific targets which were incubated with T cells expressing pancreas cancer specific CARs and T cells containing the CAR were the only cells able to kill the target cancer cells ([0111]). One of ordinary skill in the art would have a reasonable expectation of success when combining Bosio with Dose because Bosio teaches employing cancer specific target antigen recognizing moieties in CAR immune cells and Dose teaches a method of identifying cancer tissue specific target antigen recognizing moieties.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Bosio et al (EP3311832 A1), in view of Dose et al (EP3037821B1), as applied to claims 1-2, 5-10, and 15 above, and in further view of Seitz et al (Blood, 2018).
Regarding claims 3-4, the limitations of the independent claim 1 are taught above.
Bosio and Dose do not explicitly teach that the CAR T system employing the at least two antigen recognizing moieties are provided as AND-, OR-, or NOT-type as required by claim 3 or as ADAPTER-type as required by claim 4.
However, Seitz teaches that combinatorial targeting multiple antigens by adapter CAR-T (aCAR-T) allows for target cell discrimination and specific lysis based on differential expressions (abstract and pg. 1 para 2). Seitz teaches that by splitting antigen recognition and CAR-T activation, introducing an adapter molecule, the system is able to allow quantitative (on/off switch) as well as qualitative regulation of CAR-T function (pg. 1 para 2). Seitz also teaches that aCAR-Ts with AND-gate are capable of identifying and differentiating target cells based on the expression profile (pg. 2). Further, Seitz teaches that “our results indicate that aCAR-Ts in combination with selected AM combinations might have the ability to identify and specifically eliminate cancer cells based on complex antigen expression profiles. This would have major implications for clinical translation, enabling combinatorial therapy, essential to avoid antigen evasion, and the possibility to spare vitally essential tissue from elimination” (pg. 2, last para).
Regarding claims 3-4, Seitz teaches a combination adapter CAR-T cell and AND-gate logic (pg. 2, para 2).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the CAR immune cell of Bosio and Dose with the Adapter and And-type CAR-T cells by Seitz to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Seitz teaches that “our results indicate that aCAR-Ts in combination with selected AM combinations might have the ability to identify and specifically eliminate cancer cells based on complex antigen expression profiles. This would have major implications for clinical translation, enabling combinatorial therapy, essential to avoid antigen evasion, and the possibility to spare vitally essential tissue from elimination” (pg. 2, last para). One of ordinary skill in the art would have a reasonable expectation of success when combining Bosio and Dose with Seitz because Bosio teaches employing cancer specific target antigen recognizing moieties in CAR immune cells, Dose teaches a method of identifying cancer tissue specific target antigen recognizing moieties, and Seitz teaches the enhanced abilities of the CAR-T cell system when employing adapter- and and-type logic.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Bosio et al (EP3311832 A1), in view of Dose et al (EP3037821B1), as applied to claims 1-2, 5-10, and 15 above, and in further view of Lafleur et al (US20180209983A1).
Regarding claims 11-14, the limitations of the independent claim 1 are taught above.
Bosio and Dose do not teach that the CAR is specific for one or more target antigens exposed on tumor microenvironment cells selected from alpha-SMA, CD74, CXCL12, and PDGFRbeta as required by claims 11 and 12. Bosio and Dose do not teach that the CAR is specific for one or more target antigens exposed on tumor microenvironment cells selected from CD47, CD51, CD58, CD90, CD206, and CD239 as required by claims 13 and 14.
However, Lafleur et al teaches about de novo binding domain containing polypeptides which are coupled to CAR T cells for the expressed purpose of treating or preventing cancer through administering a CAR T cell which expresses a tumor antigen on its surface (abstract and [0055]). Lafleur also teaches that “In some embodiments, a combination of cancer antigens is targeted, for example by coupling or otherwise combining various target-binding polypeptides. In some embodiments, two, three, four or more different cancer antigens are targeted. In some embodiments, multiple target-binding polypeptides are used to enhance the ability and/or capacity to bind a single target (e.g., dimers, trimers, etc.)” ([0009]).
Regarding claims 11 and 12, Lafleur teaches CD74, CXCL12, and PDGFRbeta ([0162]).
Regarding claims 13 and 14, Lafleur teaches CD47, CD51 (also known as integrin AV or alpha-V), CD90, and CD239 (also known as BCAM).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the CAR immune cell of Bosio and Dose with the specific cancer target antigens taught by Lafleur to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Lafleur also teaches that “In some embodiments, a combination of cancer antigens is targeted, for example by coupling or otherwise combining various target-binding polypeptides. In some embodiments, two, three, four or more different cancer antigens are targeted. In some embodiments, multiple target-binding polypeptides are used to enhance the ability and/or capacity to bind a single target (e.g., dimers, trimers, etc.)” ([0009]). One of ordinary skill in the art would have a reasonable expectation of success when combining Bosio and Dose with Seitz because Bosio teaches employing cancer specific target antigen recognizing moieties in CAR immune cells, Dose teaches a method of identifying cancer tissue specific target antigen recognizing moieties, and Seitz teaches employing specific cancer target antigens in a coupled manner presented by CAR T cells to treat tumors.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
Prosecution Insights