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 .
Applicant’s amendment and response to restriction requirement of 2/2/26, are entered.
Claims 1-3, 5, 7-11, 14, 16, 18-20, 36, 38, 56, 58, 60, 79, 106, and 108-109 remain pending.
Election/Restrictions
Applicant’s election without traverse of Group I, as in present Claims 1-3, 5, 7-11, 14, 16, 18-20, 36, 38, and 56, in the reply filed on 2/2/26 is acknowledged.
Claims 58, 60, 79, 106, and 108-109 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/2/26.
Applicant’s election of the species of T cells specific for BKV, CMV, AdV, EBV, and HHV-6 virus antigens (element “(i)” from Claim 38), in the reply filed on 2/2/26 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)).
Claims 1-3, 5, 7-11, 14, 16, 18-20, 36, 38, and 56 are presently considered for the elected species.
Formalities:
Applicant’s priority: the present Application is a 371 of PCT/US2021/016266 (Filed 2/2/21), which in turn claims priority, as a CIP to PCT/US2020/044080 (Filed 7/29/20).
The drawings of 1/28/23 are objected to (See below).
The specification as amended 1/28/23, is accepted.
The IDS filings of 1/28/23 (three), 3/1/23, 5/5/23, 6/30/23 (two), 8/23/23, 5/30/24, 6/5/24, 6/12/24, 7/26/24, 8/2/24, 9/16/24 (two), 10/8/24, 11/14/24, 10/29/24, and 12/31/25, and the references therein, have been considered and the IDSs have been signed and are supplied herewith.
Drawings
The drawings are objected to because the contain lines and characters which are not crisp and clear (37 CFR 1.84(p) and 37 CFR 1.84(q)), and they contain characters below 1/8th an inch in height (37 CFR 1.84(p)(3)). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 2 limits the cell lines of Claim 1 to being clonal, oligoclonal, or polyclonal. These are, however, the only options. Thus, despite the slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 1 be found allowable, claim 16 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 16 requires one of the plurality of donors (the cells obtained) to match on at least two HLA alleles with the greatest number of patients in a prospective patient population. However, as the prospective patient population is not defined, it could be any population, and thus, the patient populations can be imaginary and have the required matches. Therefore, despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 1 be found allowable, claim 18 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 18 requires a T cell match that on each HLA allele with a patient in a patient population. As the patient population is imaginary, the composition is not limited. Thus, despite a slight difference in wording, these claims have the same substantial scope.
Applicant is advised that should claim 1 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 20 requires the making of the population to have been cell line generation, followed by pooling the cells. However, the cells are still in the same composition, and thus, despite a slight difference in wording, these claims have substantially the same scope.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 5, 16, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “at least two HLA alleles”, and the claim also recites “at least three HLA alleles” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 5: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “one or more Class I HLA alleles”, and the claim also recites “two or more Class I HLA alleles” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 16: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation “at least two”, and the claim also recites “at least four” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 19: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 19 recites the broad recitation “the antigen-specific T cells are derived from … 15 or fewer donors”, and the claim also recites “the antigen-specific T cells are derived from 10 or fewer donors, 5 or fewer donors” which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 5, 7, 16, 18-20 and 56 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by both U.S. Patent Application Publication 2016/0296563 and U.S. Patent No. 10,357,515, each to Sourdive, et al. (It is noted that these are the same, the patent evolving from the application, but the application is referred to for description citations (as they are labelled by paragraph), and patent claims are cited were possible because the claims are patented.
Claims 1-2: the patent claims a method of generating a batch of T cells from different human donors, and pooling the same, where they may originate from 3-50 donors (e.g., Claim 1). Claim 4 indicates they may have different HLA types, and thus they differ in the alleles. Additionally, Claim 10 indicates allele differences. E.g., Paragraph 49 of the Application Publication indicates these T cells may be T cell lines.
Claim 2: being cell lines, they are clonal, and being multiple, and from 3-50 donors, they are oligoclonal and polyclonal. Additionally, paragraphs 26-28 of the Application Publication makes clear that the cells may be clonal, and transfected to express a CAR (e.g., paragraphs 26-28).
Claims 3, 5, 7: Paragraphs 15-19 of the Application Publication teaches where minimal numbers of donors is sought for limiting infectious disease, while providing sufficient diversity for engraftment, pooling 3-50 donors, each individual expressing a small number of HLA alleles, one each of HLA A, B, and C, and the three principal class II molecules, from each parent, thereby arriving at least two allele distinctions, for each.
Claims: 16, 18 and 20: the patient population being imaginary, absent reason to believe otherwise, it does so-meet the matches and has the structure of the composition where they pooled after generation.
Claim 19: 3 donors is taught (e.g., Claim 1).
Claim 56: the structure being there, the reactivity is assumed to be present.
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.
Claim(s) 1-3, 5, 7-8, 14, 16, and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0296563 and U.S. Patent No. 10,357,515, each to Sourdive, et al. (It is noted that these are the same, the patent evolving from the application, but the application is referred to for description citations (as they are labelled by paragraph), and patent claims are cited were possible because the claims are patented.
.As shown above, the base claims are anticipated by the base art, and thus, also makes obvious the same. However, the aspect of differing for at least one class II allele is not taught.
On the other hand, each reference teaches to provide diversity through multiple donors (e.g., paragraph 15 of the patent Application Publication), i.e., in situations where a miniumal number of donors is sought to reduce infectious disease risk, while providing diversity for high engraftment, sufficient HLA diversity can be obtained by pooling lymphocytes originating from at least three donors, preferable 3-50; each individual expressing only a relatively small number of HLA alleles, A, B, and C being class I from each parent, and one allele the class II molecules (DR DP and DQ) from each parent, with little/no crossover.
Given the diversity of donors, it would therefore have been obvious to provide the same diversity in HLA alleles and Class I and Class II alleles. The Artisan would do so to provide the adqueate diversity and being able to reduced infectious disease risk. The Artisan would expect success, as it is taught for its intended purposes.
Claim(s) 1-3, 5, 7-11, 14, 16, 18, 20 and 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0296563 and U.S. Patent No. 10,357,515, each to Sourdive, et al., as applied to Claims 1-3, 5, 7-8, 14, 16, 18, 20, and 56 above, and further in view of WO 02/077030 to Jakobsen, et al.
As shown above, the base claims are obvious over the base art (the publication or the patent), however, the aspect of differing from the DPA1, DPB1, DQA1, DQB1, DRA and DRB1 is not taught.
Claims 9-11:
On the other hand, Avidex teaches the DRA and DRB1 class II alleles are associated with disease (e.g., p. 9, teaching the DRA is a clas II alpha chain, while the DRB1 is a class II beta chain, DR denoting the loci in which the DNA encoding the HLA class II molecule is located, the class II HLA loci being DM, DO, DP, DQ and DR. Each complete class II HLA containing alpha and beta chains, from the same loci. “A” and “B” denote the alpha or beta chain of an HLA, respectively. The remaining numbers follow the same rules. Class II disease associations are produced by antigen peptide specificity, which can be induced by alpha or beta chains of any given HLA molecule. By convention, these disease associations are listed by reference to the class II HLA chain associated with the disease. Generation of the cells of cells present HLA alles of distinct types is also taught: “modified molecules of a selected HLA type are caused to be presented by a cell. The modified molecules can be different subtypes.
Given that two HLA class II alleles are known and prominent in patients, it would have been obvious to the Artisan to use these alleles in the T cells, thus, making a population meeting the claim., and differences. The Artisan woudl do so to optimize the universal potential of the cells for distinct recipients. The Artisan would expect success, as the components are utilized for art-recognized purposes.
Claim(s) 1-3, 5, 7-11, 14, 16, 18, 20, 36, 38 and 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0296563 and U.S. Patent No. 10,357,515, each to Sourdive, et al., as applied to Claims 1-3, 5, 7-8, 14, 16, 18, 20, and 56 above, and further in view of Siyahian, et al. (2018 July) “Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A systematic Review and Meta-Analysis” Biological Blood Marrow Transplant, 24(7): 1483-89.
The various aspects are obvious over the base art, however, the aspect of targeting HBV is not taught, although Sourdive claims treating viral infection (e.g., Claim 19).
On the other hand, Siyahian teaches treating Hepatitis B reactivation after allogeneic stem cell transplant (e.g., ABSTRACT).
Thus, it would be obvious to use T cells for HBV, and follow that with further treatment if reactivation occurs. The Artisan would do so, as allogeneic T cell treatment was already known for HBV. The Artisan would expect success, as the components are utilized for their art-recognized purposes.
Art Made of Record
Inventor Leen’s NPL: Melenhorst, et al. (2010) “Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects”, Blood, 116(22); 4700-02, which appears to be the first study to note that allogeneic T cells do not produce GVHD in humans.
Conclusion
No claim is allowed.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638