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 .
The examiner of your application in the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Brian Whiteman, Art Unit 1636.
Election/Restrictions
Applicant’s election of group I (claims 1, 2, 6, 7, and 10-19) and species (atezolizumab and small cell lung cancer (SCLC)) in the reply filed on 5/7/26 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)).
NOTE: claim 10 was cancelled in the amendment filed on 5/7/26.
Upon further consideration, the species requirement is withdrawn and all non-elected species are rejoined with the elected species and are searched and examined..
Claims 3-5 and 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/7/26.
Information Disclosure Statement
The references cited in the PCT international search report by the European Patent Office have been considered, but will not be listed on any patent resulting from this application because if they were not provided on a separate list in compliance with 37 CFR 1.98(a)(1). In order to have the references printed on such resulting patent if it was not already cited on a 1449, a separate listing, preferably on a PTO/SB/08 form, must be filed within the set period for reply to this Office action.
The report on patentability of the IPEA and/or ISA has been considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claims 1 and 6 are objected to because of the following informalities: the carrot symbol is objected to because it is not considered a proper symbol and might have an issue being printed if the claims are issued as a US patent. See MPEP 608.01(m). Suggest replacing the symbol with a hyphen, number or letter.
The parenthesis in the term (<) and (≥) in claim 1 should be removed because it is not an example of a term, but the term is indicating that the immune subset if below a median percent of activated T cells or at least 20%.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 6, 7, 11-16, and 18-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention embraces a method of treating cancer in a genus of patients comprising administering to the patients a TLR9 agonist comprising a CG dinucleotide having at least three nonmethylated CG dinucleotides, wherein the patient is administered the TLR9 agonist after having undergone induction chemotherapy consisting of a first set of treatment cycles and the patient is assigned a status of “non-matched in first” in a predictive biomarker assay or a “matched in second” based on precent of Treg cells among CD4+ T cells in a sample.
Instant claims 18 and 19, the as-field specification and the art of record disclose that induction chemotherapy is well-known in the prior art. However, the claimed method embraces a large number of cancer each with distinct clinical behaviors, treatment strategies and outcomes.
The specification of the instant disclosure provides sufficient description of patients having SCLC, wherein the patient is assigned a status of “non-matched in first” or “matched in part”, however SCLC is not considered a representative species of cancer for one of skill in the art to envision a subject having a different type of cancer could be assigned the status set forth for a patient having SCLC.
The claimed invention involves assigning the patient based on assay involving determining the percent of activated cells within an immune cell subset selected from B cells, T cells, natural killer T (NKT) cells, dendritic cells (DC), plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC), and/or Treg cells among CD4+ T cells in a blood sample from the cancer patient.
The prior art, Schroff (US 20160115479), teaches an assay involving determining the percent of activated cells within an immune cell subset selected from B cells, T cells, natural killer T (NKT) cells, dendritic cells (DC), plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC), and/or Treg cells among CD4+ T cells in a blood sample from a cancer patient.
Tan et al. (Frontier in Oncology 12:958756, pages 1-7, 2022) teach different B cells phenotypes in various cancer (figure 1).
Waldman et al. (Nat Rev Immunol 2020 20: 651-668) teach T cell activity in cancer is not uniform, it varies depending on the cancer type, tumor microenvironment and immune context. Their function, phenotype, and abundance differ across cancers.
Kim et al. (Cancer Immunol Res 2, 91-98, 2014) teach, “Tumor immunity is a sum of complex interactions between cells in the tumor microenvironment (page 96).” Kim further teaches the frequence of Tregs in tumor environments is from 20% to 30% depending the type of tumor (page 94).
The claimed invention embraces a large number of cancers involving different organs, tissues and/or cells of a subject. The cancer can be hot or cold (page 3 of the specification). “Hot” tumors are classified by high infiltration of cytotoxic lymphocytes and leukocytes in the tumor microenvironment. “Cold” tumors are poorly immunogenic and characterized by lower lymphocyte infiltration in to the tumor and lack of pre-existing tumor specific T cell response. The cancer could embrace cancer that is resistant or sensitive to chemotherapy and/or TLR9 agonist.
Depending on the type of cancer, there appears to be variation in results amongst assays involving activated cells, including B cells and T cells. Thus, in view the art of record, the skilled artisan could not envision the results for an assay for a blood sample from a subject having one type of cancer would represent results from an assay for a subject having a different type of cancer.
The specification does not provide written description for the claimed genus of patients based on an assay involving activated cells because the specification does not satisfy written description of the genus through sufficient description of a representative number of species of results from assays for different types of cancer using a blood sample. There is a substantial variation within the genus of cancers and the applicant does not describe a sufficient variety of species of assays involving activated cells to reflect the variation within the genus. See Enzo Biochem., 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). See also MPEP §2163.
In view of the foregoing, it is clear that the specification of the instant disclosure fails to convey to the skilled artisan that the applicant had possession of the claimed genus of patients after undergoing induction chemotherapy have been assigned a status of “non-matched in first” in a first predictive assay involving activated cells and a patient is assigned a status of “matches-in-second” if the percent of Treg cells among CD4+ T cells in the sample is at least ≥ 20% in claims as of the effective filing date.
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 2, 6, 7, and 15-19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 2, 6, 7, and 15-19, the phrase "particularly" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 6 recites the limitation "the CPM maintenance immunomodulation regime" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the TLR9 maintenance immunomodulation regime" in line 20. There is insufficient antecedent basis for this limitation in the claim. NOTE: the limitation further recites “as specified in claim 1”, but claim 6 is already dependent on claim 1.
Conclusion
See attached PTO-326 for disposition of claims.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The closest prior art, EP3392345 or Thomas et al. (Annals of Oncology Vol. 29, 2018, pages 2076-2084), both cited on an IDS, teaches using TLR9 agonist (Leftitolimod) recited in the claimed methods to treat cancer in a subject. Schroff (US 20160115479) teaches an assay involving determining the percent of activated cells within an immune cell subset selected from B cells, T cells, NKT cells, DC, pDC, mDC, and/or Treg cells among CD4+ T cells in a blood sample from a cancer patient. However, the prior art does not teach or suggest the method steps involving the definition of the subject used in the method. As evidenced by the written opinion of the international searching authority for the international application (PCT/EP2022/066533) of the instant application filed on 12/17/23, the combination of steps are not made taught or made obvious by the prior art of record. See pages 7-10 of the written opinion, incorporated herein. See also pages 2-3 of the as-filed specification.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571)-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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