Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Amendments
In the reply filed 10/28/2025, Applicant has made no amendments to the claims.
Claims 1-8, 10-13, 15-22 are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/29/2025 was filed after the mailing date of the non-final Office action on 8/05/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed by Dr. Malcolm Brenner on 10/28/2025 has been considered but is insufficient to overcome the rejection of instant claims based upon 35 U.S.C 103(a) as set forth in the last Office action for the reasons explained below.
Maintained Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) 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.
Claims 1-8, 10-13, 15-22 stand rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Berenson et al. (WO 2006/133398), in view of Anasetti et al., Blood, 1988, 72:1099-1100), Straathof et al., (Blood, 2005, 105:4247-4254) and Quintarelli et al., (Blood, 2007, 110:2793-2802)
In regard to claims 1(a) and 16(a), Berenson et al. teaches methods of cell therapy comprising administering allogeneic T cells to a transplant patient for the treatment of a malignancy (p. 2, Summary of the Invention, 1st line and last para.).
In regard to the transplant patient, Berenson teaches the subject is human in need of treatment (p. 43, 2nd para., p. 51, 2nd para.).
In regard to the allogeneic T cells, Berenson teaches the T cells are from an allogeneic human donor which comprise a mismatch at a loci that influences graft rejection (p. 11, 2nd para., p. 14, last para. to p. 15, 1st para.). Although Berenson is silent to non-allodepleted allogenic T cells, Berenson cites the work of other studies such as Anasetti et al., 1988 that were carried out in human transplant patients with human non-allodepleted “buffy-coat” derived allogeneic T cells (p. 13, lines 15-20).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize the method as taught by Berenson and to choose the non-allodepleted allogenic T cells as taught by Anasetti with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Anasetti teaches that the non-allodepleted T cells despite being more immunogenic result in a better treatment outcome (p. 1099, Fig. 1 of Anasetti). Second, Berenson teaches that mismatches between the allogeneic donor T cells and the patients is desirable because the mismatch promotes graft-vs-leukemia (GVL) effects of the donor lymphocytes (p. 14, last para.).
However, in regard to claims 1 (a)(i/ii) and 16 (a)(i/ii), as per the steps of expressing in the T cells a nucleic acid comprising a promoter region and encoding a FKBP based caspase 9 fusion protein, although Berenson teaches the cells comprise a polynucleotide that encodes chimeric protein that regulates T cell survival, comprising a multimeric ligand binding region of human FKBP fused to human caspase 9 (p. 32, last para.), they are silent with respect to the T cells expressing a nucleic acid comprising a promoter region and encoding a FKBP12 and caspase 9 fusion protein after a transfection step.
Nevertheless, Berenson cites the work of Straathof et al., 2005, for the description of the modified human caspase 9 fused to human FKBP (p. 32, last para.),
In regard to claims 1(a) and 16(a), Straathof et al., 2005, teaches a method of administering human donor T cells transfected with a nucleic acid comprising a promoter operably linked caspase 9 polypeptide fused to the multimeric ligand binding domain of FKBP12 comprising a F36V substitution (p. 4248, Plasmids, see Fig. 2, p. 4249, In vivo experiments, see Fig. 7). Furthermore, Straathof teaches that the F36V substitution changes the binding of FKBP from its natural ligand to a synthetic inducer AP1903 that has been proven safe in human volunteers (p. 4247, Intro, 2nd para.).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize the method as taught by Berenson and choose the FKBP12 F36V modified caspase 9 nucleic acid operably linked to a promoter as taught by Straathof with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Straathof teaches that the inducible caspase 9-FKBP12 fusion protein is made entirely of human proteins and it therefore not immunogenic like other suicide genes (p. 4247, Intro, 2nd para.). Furthermore, the ordinary skilled artisan would have been motivated to do so because Berenson explicitly directs the artisan to the method of Straathof, and this method is taught as being an effective “inducible safety switch” for treating in vivo graft vs. host disease mediated by aberrant donor T cells (Abstract, p. 4247, Introduction, 2nd para., p. 4253, last para. of Straathof).
However, in regard to claims 1(b) and 16(b/c), although Berenson teaches the step of administering a ligand to the patient to whom the donor T cells have been infused so as to allow for the ligand based removal (“killing”) of the infused donor T cells (p. 32, lines 20-23), they are silent to the patient exhibiting graft-vs-host disease.
Nevertheless, Straathoff teaches the method step of administering the multimeric ligand AP1903 that binds to the FKBP12 domain of the iCas9 fusion so as to reduce the number of donor T cells (p. 4249, In vivo experiments, see Fig. 7). Furthermore, as stated supra, Straathof teaches that the administration step is to cause the destruction of T cells causing graft-vs-host disease.
Accordingly, it would have been obvious to one of ordinary skill practicing the method of Berenson in view of Straathoff that the step of administering a multimeric ligand for the “killing” of infused donor T cells was to be performed for treating in vivo graft vs. host disease mediated by the alloreactive donor T cells.
Finally, in regard to the % reduction clauses of claims 1 and 16 (as well as claims 10 and 21) directed to the efficiency of the method, although Straathof demonstrates that there is greater than 99% depletion efficiency of highly expressing iCasp9-FKBP12 modified T cells three days after the ligand is administered in vivo (p. 4252, Fig. 7, see also Results, last para.), Berenson and Straathof are silent with respect to the depletion efficiency in vivo being greater than 90% depletion efficiency one day after the ligand is administered (or 1/2 hour after ligand administration as per claims 10 and 21).
Nevertheless, Quintarelli et al., who share’s co-authors with Straathof, teaches a method of treating a patient with modified T cells comprising the same iCasp9-FKBP12-F36V as Straathof (see p. 2798, col 1 refers to the publication of Straathof as the source of the suicide gene). Specifically, Quintarelli demonstrates that there is greater than 90% depletion of modified T cells about 24 hours from the time of ligand administration (p. 2798, col 1, see also Fig. 7 & legend) and in regard to claims 10 and 21, Quintarelli appears to demonstrate there is an immediate reduction of T cell bioluminescence as soon as the ligand is administered in vivo (Fig. 7B). Thus, Berenson in view of Straathof and Quintarelli make obvious all of the steps to arrive at the claimed outcome for claims 1, 10, 16, and 21.
In regard to claims 2 and 17, Berenson teaches the T cells are polyclonal (p. 13, last para., p. 30, 1st para.).
In regard to claims 4 and 5, as stated supra, Berenson cites Straathof, who teaches that expression of the caspase 9-FKBP chimeric protein does not affect the phenotype or function of the modified T cells (p.4250, 3rd para., Fig. 3). Thus, Straathof suggests that the phenotype and function of the surviving modified T cells would have been unchanged after administration of the multimeric ligand. Furthermore, the Examiner has determined that the phrase describing the surviving T cells as “able to expand and are reactive to” viruses and fungi as per claim 4 or the patient’s tumor cells per claim 5 as not resulting in a structural difference (or, in this case of a process claim, a manipulative difference) between the claimed invention and the prior art (see MPEP 2111.02(II)). In instant case, the modified T cells of Berenson should have been able to expand and react to any antigen presented by an antigen-presenting cell.
In regard to claims 6 and 18, Berenson teaches the modified T cells can be administered after a stem cell transplant (p. 37, last para.), and specifically suggests a haploidentical stem cell transplant in order to increase engraftment (p. 39, 1st para.).
In regard to claims 7-8 and 19, as stated supra, Berenson cites Straathof, who teaches that the chimeric protein further comprises a selectable marker using either an IRES or 2A sequence, which allows for selection of high transgene-expressing T cells (p. 4253, Discussion, 1st para.). Furthermore, Quintarelli teaches the steps of enriching for the highest transgene expressing iCasp9-FKBP12 modified T cells using a CD34 marker in order to ensure that all of the cells are responsive (p. 2795, col 2, 2nd para.). Accordingly, it would have been obvious to combine a maker and selection step in the method of Berenson with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Quintarelli in order to ensure that all of the cells are responsive to the multimeric ligand (p. 2795, col 2, 2nd para.).
In regard to claims 3, 11 and 12, Berenson teaches the allogeneic T cells are not in an activated state when administered to the patient so as to generate helper T cell responses (p. 27, last para., p. 29, 1st para.). Specifically in regard to claim 12, Berenson defines the quiescent state of the cell as one where the cell has not been induced to actively proliferate (p. 10, 2nd para.), thereby generating a greater proportion of the CD4+ helper cells, which Berenson teaches is advantageous to induce a graft-vs-leukemia response (p. 27, last para.). Furthermore, as stated supra, Berenson cites the successful use of freshly isolated allogenic donor T cells in the methods of Anasetti, wherein the non-stimulated T cells despite being more immunogenic result in a better treatment outcome. In regard to claim 3, Straathoff teaches that since the caspase 9-FKBP chimeric protein induces T cell death via apoptosis, cell division is not required for cell death unlike the HSV-thymidine kinase suicide genes (p. 4247, Introduction).
In regard to claims 13 and 22, as stated supra, Berenson cites Straathof, who teaches that the multimeric ligand binding domain of the chimeric protein comprises two FKBP12 polypeptides linked by a SGGGS linker, wherein one of the FKBP polypeptides is codon wobbled (p. 4248, Fig. 2, see legend). Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to substitute wobbled codons for the FKBP fusion protein as taught by Straathof with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because Straathoff teaches that wobbled codons prevent homologous recombination of the vector (p. 4248, Fig. 2, legend of Straathof).
In regard to claims 15 and 20, as stated supra, Berenson cites Straathof, who teaches that the caspase chimeric protein is a "truncated caspase molecule", which significantly increased the caspase 9 activity (p. 4248, Fig. 2A).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments and the declaration under 37 CFR 1.132 filed by Dr. Malcolm Brenner on 10/28/2025 are acknowledged.
First, Applicant argues that Berenson is silent to non-allodepleted allogeneic T cells, and Anasetti does not cure this deficiency because Anansetti is directed to administering donor buffer coat containing cells, which is a mixed cell population and not non-allodepleted allogeneic T cells.
Second, Applicant argues that Berenson is silent to the nucleic acid with a promoter and FKBP12 and caspase 9 fusion, and Straathof does not cure this deficiency because Straathof does not use the nucleic acid in non-allodepleted allogeneic T cells.
Third, Applicant argues that Berenson teaches the use of the suicide gene system for killing infused donor T cells and is silent for treating graft vs host disease symptoms caused by the donor T cells, and Straaathof does not cure this deficiency because their work is in a SCID mouse xenograft model using EBV-specific T cell lines, not human patients with clinical GvHD. Neither Berenson or Straathof reduce to practice the claimed clinical steps of infusing the donor T cells, waiting until GvHD, and administering the multimeric ligand to achieve the claimed outcome.
Fourth, Applicant argues that there was no reasonable expectation of success in practicing the claimed invention because Berenson is silent to an efficiency of reducing the number of T cells in vivo, and Quintarelli presents preclinical animal models and signal readouts that cannot be equated to the human.
Fifth, Applicant argues and Dr. Brenner declares that the claimed method yielded unexpected results in human patients, wherein activation of iCasp9 by AP1903 rapidly ablated alloreactive donor T cells by greater than 90% within 24 hours, and in some instances, within about 30 minutes, concurrent with symptom relief as demonstrated in Figs. 30-35 of instant Application, and Exhibits C-F of the Brenner declaration.
Applicant's arguments and the declaration under 37 CFR 1.132 filed by Dr. Malcolm Brenner have been fully considered but they are not persuasive.
In response to Applicant's first argument, a 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In instant case, Berenson clearly teaches allogeneic T cells. Furthermore, contrary to Applicant’s assertion, the buffy coat suspension of cells administered by Anasetti are clearly non-allodepleted because there was no depletion step, and were clearly allogeneic because they came directly from a donor other than the patient, and these properties would have been well-known by one of ordinary skill in the art at the time of filing. Furthermore, Anasetti provides good reason to use non-allodepleted allogeneic T cells because they are more immunoreactive since they contain the full range of a donor’s white blood cells, whare are the source of alloreactivity. Finally, the claimed method does not limit the T cell population to a purified or isolated non-allodepleted allogeneic T cells, thus even a mixture of buffy coat cells from a donor that would naturally have non-allodepleted allogeneic T cells meets the limitations of the claim.
In response to Applicant’s second argument, it has been held that the test for obviousness is not whether the features of one reference may be bodily incorporated into the other to produce the claimed subject matter but simply what the combination of references makes obvious to one of ordinary skill in the pertinent art. In re Bozek, 163 USPQ 545 (CCPA 1969). In instant case, Berenson teaches the inducible suicide gene system based on “dimerizable, modified human caspase9 fused to human FK506 binding protein (FKBP)” and explicitly directs the skilled artisan to the prior art of Straathof (p. 32, last para of Berenson), who teaches the advantages of the iCasp9 system as being efficient, made entirely from human components, and uses a multimeric ligand that has proven safe in human clinical trials.
In response to Applicant’s third argument directed to the GvHD patient and clinical steps (the outcomes will be addressed in the fourth response to arguments), as stated supra, a 35 U.S.C. § 103(a) based test for obviousness is based on what the combined teachings of the references would have suggested to those of ordinary skill in the art. Straathof clearly teaches that the purpose of the iCasp9 system was to cause “destruction of T cells causing graft-versus-host disease”, wherein other systems had failed to do so (Introduction, 2nd para.), and that the systems was “safety switch for clinical applications” (Discussion, p. 4252, last para., see also the title of Straathof “Inducible safety switch for T-cell therapy”). Accordingly, it would have been obvious to practice the method of Berenson in view of Straathoff, wherein the step of administering a multimeric ligand for the “killing” of infused donor T cells was to be performed for treating graft vs. host disease mediated by the donor T cells. As far as a reduction to practice of steps of administering the genetically modified T cells, waiting for GvHD, and administering the ligand, the first and third of these three steps are explicitly taught in the prior art; and as far as the waiting step, this is implicit in the teachings of the prior art so as to achieve “destruction of T cells causing graft-versus-host disease”.
In response to Applicant’s fourth argument directed to the reasonable expectation of success, Berenson is clearly directed to human transplantation of T lymphocytes (Title and Abstract). Moreover, as state supra, Straathoff teaches that the iCasp9 suicide system is made of human components, and the AP1903 ligand had proven safe in a clinical trial in human volunteers. Thus, there was a reasonable expectation of success in making and using AP1903 to kill human T cells comprising the human iCasp9 system in human subjects. In regard to achieving the 90% killing efficiency as claimed, Quintarelli teaches in an animal model that using AP1903 to kill T cells comprising the iCasp9 system killed 90% of cells within 24 hours and apparently killed 90% of cells in about 30 min. Thus, the animal model certainly does not contradict the possibility of the same effect in humans and provides tacit evidence that such a result could have been achieved in humans with the same system. Applicant is reminded that any conclusions of unpredictability in humans have to be made in the context of state of the art with the closest animal models, wherein the existence of established animal models of high efficiency killing of iCasp9 transduced T cells by administration of AP1903 or AP20187 provided a reasonable amount of predictability for the same to occur in a human. Furthermore, the Federal Circuit would have found that the claims at issue would have been obvious since there had been ample suggestion in the prior art that the claimed method would have worked. Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. The Federal Circuit concluded that Applicant’s “[g]ood science and useful contributions do not necessarily result in patentability.” Id. at 1364, 83 USPQ2d at 1304.
In response to Applicant’s fifth argument, and Dr. Brenner’s declaration of unexpected results. The Examiner acknowledges that the efficient and rapid elimination of the donor T cells comprising the FKBP12-F36V iCasp9 system, GvHD symptoms, and cytokine responses in a human patient after administration of AP1903 was significant and is a clinical milestone worthy of secondary considerations. However, the unexpected results presented by the declaration do not show that the objective evidence of nonobviousness is commensurate in scope with the claims. See MPEP § 716. Importantly, Applicant’s claims are directed to any FKBP12 fusion protein, and any multimeric ligand including FK506 itself (see [0158] of specification). In order to complete the art of record and to rebut Applicant's arguments, Applicant is directed to the prior art of Clackson et al. (PNAS, 1998, 95:10437, see IDS filed 10/28/2025), which demonstrates that the nature of the FKBP and multimeric agent were critical to the efficacy of the multimeric ligand in vivo. Clackson evidences that multimeric ligands such as AP1903 were specifically designed to bind FKBP12 mutants comprising a F36V substitution in the ligand binding pocket, which increased binding affinity by a 1000-fold. Furthermore, Clackson evidences that although the multimeric ligands were based on a naturally occurring ligand of FKBP12 (i.e., FK506/tacrolimus), these synthetic ligands were not complicated by their potential interaction with endogenous FKBPs in vivo (Abstract & Introduction). As stated supra, Dr. Brenner only demonstrated unexpected results for a single type of FKBP12 polypeptide (i.e, the FKBP12-F36V mutant) and a single type of multimeric ligand (i.e. the FK506 analog of AP1903).
Applicant is reminded that a showing of unexpected results for a single member of a claimed subgenus, is not always sufficient to rebut a prima facie case of obviousness, see MPEP 2145, Grasselli, 713 F.2d at 743, 218 USPQ at 778 (evidence of superior properties for sodium containing composition insufficient to establish the non-obviousness of broad claims for a catalyst with “an alkali metal” where it was well known in the catalyst art that different alkali metals were not interchangeable and applicant had shown unexpected results only for sodium containing materials); In re Greenfield, 571 F.2d 1185, 1189, 197 USPQ 227, 230 (CCPA 1978) (evidence of superior properties in one species insufficient to establish the nonobviousness of a subgenus containing hundreds of compounds); In re Lindner, 457 F.2d 506, 508, 173 USPQ 356, 358 (CCPA 1972) (one test not sufficient where there was no adequate basis for concluding the other claimed compounds would behave the same way).
In instant case, it was well known in the FKBP art that different FKBP12 proteins and multimeric ligands were not interchangeable, and since Applicant and Dr. Brenner had shown unexpected results only for the FKBP12-F36V mutant and the multimeric ligands of AP1903, the claims are not commensurate in scope with unexpected results.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-7, 10-13, 15-22 are rejected on the grounds of nonstatutory double patenting over claims 1-36 of U.S. Patent No. 11,077,176 (Malcolm Brenner, Patented 8/03/2021).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for treating a human patient who had received non-allodepleted allogeneic T cells using a multimeric ligand of cited patent makes obvious the methods of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims do not explicitly recite that the human patient exhibits graft-vs-host disease. Nevertheless, this is clearly the intended patient population as evidenced by the specification, and would have been obvious to treat this patient population considering the well known graft-vs-host effects of administering non-allodepleted allogenic T cells.
Since the instant application claims are made obvious by cited patent claims, said claims are not patentably distinct.
Claim 8 is rejected on the grounds of nonstatutory double patenting over claims 1-36 of U.S. Patent No. 11,077,176 (Malcolm Brenner, Patented 8/03/2021), in view of Quintarelli et al., (Blood, 2007, 110:2793-2802).
As stated supra, the method for treating a human patient who had received non-allodepleted allogeneic T cells using a multimeric ligand of cited patent makes obvious the methods of instant application.
However, the difference between the cited patent claims and the instant claims lies in the fact that although the cited patent claims do recite a marker, they not explicitly recite a selection step for T cells with the marker for administration to the human patient.
Nevertheless, Quintarelli et al., teaches the steps of enriching for the highest transgene expressing iCasp9-FKBP12 modified T cells using a CD34 marker in order to ensure that all of the cells are responsive (p. 2795, col 2, 2nd para.). Accordingly, it would have been obvious to have claimed selection step in the cited patent with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Quintarelli in order to ensure that all of the cells are responsive to the multimeric ligand (p. 2795, col 2, 2nd para.).
Since the instant application claims are made obvious by cited patent claims in view of Quintarelli et al., said claims are not patentably distinct.
Claims 1-7, 10-13, 15-22 are rejected on the grounds of nonstatutory double patenting over claims 1-34 of U.S. Patent No. 9,393,292 (Malcolm Brenner, Patented 7/19/2016).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for controlling survival of non-allodepleted allogeneic T cells using a multimeric ligand in a human patient makes obvious the methods of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims do not explicitly recite that the human patient exhibits graft-vs-host disease. Nevertheless, this is clearly the intended patient population as evidenced by the specification, and would have been obvious to treat this patient population considering the well known graft-vs-host effects of administering non-allodepleted allogenic T cells.
Since the instant application claims are made obvious by cited patent claims, said claims are not patentably distinct.
Claim 8 is rejected on the grounds of nonstatutory double patenting over claims 1-34 of U.S. Patent No. 9,393,292 (Malcolm Brenner, Patented 7/19/2016), in view of Quintarelli et al., (Blood, 2007, 110:2793-2802).
As stated supra, method for controlling survival of non-allodepleted allogeneic T cells using a multimeric ligand in a human patient makes obvious the methods of instant application.
However, the difference between the cited patent claims and the instant claims lies in the fact that although the cited patent claims do recite a marker, they not explicitly recite a selection step for T cells with the marker for administration to the human patient.
Nevertheless, Quintarelli et al., teaches the steps of enriching for the highest transgene expressing iCasp9-FKBP12 modified T cells using a CD34 marker in order to ensure that all of the cells are responsive (p. 2795, col 2, 2nd para.). Accordingly, it would have been obvious to have claimed selection step in the cited patent with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Quintarelli in order to ensure that all of the cells are responsive to the multimeric ligand (p. 2795, col 2, 2nd para.).
Since the instant application claims are made obvious by cited patent claims in view of Quintarelli et al., said claims are not patentably distinct.
Claims 1-8, 10-13, 15-22 are rejected on the grounds of nonstatutory double patenting over claims 1-24 of U.S. Patent No. 9,089,520 (Malcolm Brenner, Patented 7/28/2015).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the method for treating graft-vs-host disease in a human patient having been administered non-allodepleted allogeneic T cells using a multimeric ligand anticipates the methods of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific with respect to the chimeric protein and multimeric ligand. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of instant claims. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited patent claims, said claims are not patentably distinct.
Response to Arguments
Applicant asks that the nonstatutory double patenting rejections be held in abeyance.
Conclusion
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
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