DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 07/22/2026 has been entered. Claims 1-14 are pending in this application. Claims 3-5, 7-10, and 12-14 are withdrawn. Claims 1, 2, 6, and 11 are currently under examination.
Priority
This application is a CON of PCT/US2022/028915 filed on 05/12/2022 and claims benefit of US PRO 63/313,251 filed on 02/23/2022 and US PRO 63/188,970 filed on 05/14/2021.
Election/Restrictions
Applicant's election without traverse of Group I invention (claims 1, 2, 6, and 11) and species (prostate cancer) in the reply filed on 07/22/2026 is acknowledged. Claims 3-5, 7-10, and 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1, 2, 6, and 11 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 08/30/2024 has been considered.
Claim Objections
Claims 1, 2, 6, and 11 are objected to because of the following informalities: In claim 1, insert the missing phrase “in need thereof” immediately after the recitation “subject” (line 2), because a subject encompasses any healthy subject who does not require such treatment. In claim 2, change the recitation “claim 1, comprising” (line 1) to “claim 1, wherein the method comprises” to become proper dependent claim format. In claims 6 and 11, change the incorrect conjunction “or” (line 2 of claims 6 and 11) to “and” to comply with Markush group format beginning with “selected from the group consisting of” and ending with the conjunction “and” before the last species. 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, and 11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a tumor in a subject in need thereof, does not reasonably provide enablement for preventing or reducing the risk of a tumor in a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or to use the invention commensurate in scope with these claims. Claims 2, 6, and 11 depend from claim 1.
Applicants claim a method of preventing or reducing the risk of a tumor in a subject recited in claim 1. However, no limiting definition of “preventing" or “reducing the risk (equivalent to prevention)” is given in the Specification. In the absence of a limiting definition by the Applicants, "prevention" as described according to the Institute for International Medical Education (pages 15 and 16), is a preventive measure, such as preserving physical fitness in primary prevention and effective intervention to correct departures from good health in secondary prevention. More specifically, tertiary prevention, which is most relevant as used in the context of the instant invention, "consists of the measures available to reduce or eliminate long-term impairments and disabilities, [and to] minimize suffering caused by existing departures from good health". Thus, the claimed method of preventing or reducing the risk (equivalent to prevention) of a tumor in a subject as interpreted by a skilled practitioner of the medical or pharmaceutical arts would be to reduce for long-term the occurrence of or to eliminate a tumor in a subject by the method.
The Applicant's attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The rejected invention is drawn to A method of treating, preventing, or reducing the risk of a tumor in a subject, the method comprising reducing the amount of one or more proteins selected from the group consisting of EGR1, NR3C1, PBX4, MAFB, ID2, STAT4, NR4A3, NR4A1, TRPS1, EGR3, BANP, ZEB2, KLF4, GLI1, CSRNP2, KDM2B, and FOSL2.
Relative skill of those in the art: The relative skill of those in the art is from biomedical field.
Breadth of claims: The claim is extremely broad in that it encompasses the prevention of a tumor in a subject using the instantly claimed method.
State of the prior art/Predictability or unpredictability of the art: There is no teaching or suggestion in the state of the prior art that application of certain pharmaceutical method can prevent a tumor in a subject. Safford et al. (NATURE IMMUNOLOGY VOLUME 6 NUMBER 5, 472-480, MAY 2005) disclosed that overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation. Conversely, T cells from Egr3-/- mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance. For tumor immunotherapy, perhaps strategies should be aimed at blocking tumor-induced tolerance by inhibiting Egr-2 and Egr-3 upregulation while at the same time leaving TCR-induced positive activation intact (page 472, Abstract; page 479, left col., para. 1). One of skilled artisan would understand that contemporary treatment or management of a tumor via immune modulation is to minimize symptom, not to prevent or to reduce the risk of a tumor.
Amount of guidance/Existence of working examples: It is worth noting that there are no working examples in the instant application to show that the claimed method is effective for preventing or reducing the risk of a tumor in a subject as recited in the claim. The exemplary embodiments of the Specification merely present: (I) EXAMPLE 1: General Concept, (II) EXAMPLE 2: Treg Tumor-infiltration Master Regulators, (III) EXAMPLE 3: Candidate MR Validation by In Vivo Pooled CRISPR-KO Screen, (IV) EXAMPLE 4: Drug Screening in Human Tregs Identifies Tumor-Treg Directed Therapeutic Candidates, (V) EXAMPLE 5: Low-Dose Gemcitabine inhibits tumor viability preferentially in immunocompetent mice, (VI) EXAMPLE 6: Clinical Sample Collection, Sorting, and RNA-Sequencing, and (VII) EXAMPLE 7: Applying VIPER protein activity inference on a novel dataset of TI-Tregs, P-Tregs, and additional CD4 and CD8 non-Treg controls across 36 patients, we defined a set of 17 TI-Treg MRs (EGR1, NR3C1, PBX4, MAFB, ID2, STAT4, NR4A3, NR4A1, TRPS1, EGR3, BANP, ZEB2, KLF4, GLI1, CSRNP2, KDM2B, FOSL2) (p. 8-32).
Quantity of experimentation: In order to practice the full scope of the invention, one skilled in the art would need to undertake a novel and extensive research program to show that a preventive measure can be achieved after applying the claimed method. Furthermore, one of ordinary skill in the art would need to test a representative number of animals before one of ordinary skill in the art would be able to conclude that any method can be used to prevent a tumor in a subject. Because this research would have to be exhaustive, and because it would involve such a wide and unpredictable scope of use in prevention of a tumor in a subject, it would constitute an undue and unpredictable experimental burden.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164. Genetech, 108 F.3d at 1366, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Therefore, in view of the Wands factors as discussed above, including the amount of guidance provided and the predictability of the art and the lack of working examples to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 6, and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon or a product of nature without significantly more. The 2019 Revised Patent Subject Matter Eligibility Guidance (issued January 7, 2019)” (https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf) and “October 2019 Update: Subject Matter Eligibility (issued October 17, 2019)” (https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf), are followed here. The claim is directed to a statutory category, e.g., a process (Step 1: YES). The claim is then analyzed in Step 2A (Prong one) to determine whether it is directed to any judicial exception. Claim 1 recites a method comprising reducing the amount of one or more proteins selected from the group consisting of EGR1, NR3C1, PBX4, MAFB, ID2, STAT4, NR4A3, NR4A1, TRPS1, EGR3, BANP, ZEB2, KLF4, GLI1, CSRNP2, KDM2B, and FOSL2, which encompass a process of pathological reduction of one or more proteins selected from the group consisting of EGR1, NR3C1, PBX4, MAFB, ID2, STAT4, NR4A3, NR4A1, TRPS1, EGR3, BANP, ZEB2, KLF4, GLI1, CSRNP2, KDM2B, and FOSL2 in a tumor, and thus are natural phenomenon. Accordingly, the claim is directed to at least one exception (Step 2A, prong one: YES). The claim is then analyzed in Step 2A (Prong two) and is deemed that this judicial exception is not integrated into a practical application because there is no indication that the reducing step requires administering any agent. Instead, some tumor types acquire reduction of one or more of claimed proteins in the process of tumorigenesis. Thus, the claimed process as a whole does not display markedly different characteristics compared to the closest naturally occurring process. Accordingly, the Step 2A (Prong two) is NO because this judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because prior to applicant’s invention and at the time of filing the application, reduction of one or more of claimed proteins were well-understood, routine and conventional in the field, as evidenced by the references under the 102 rejection below. Thus, the claimed method, when recited at this high level of generality, does not meaningfully limit the claim, and the claim as a whole does not amount to significantly more than each “natural phenomenon” by itself (Step 2B: NO). The claim does not qualify as eligible subject matter.
Claim Rejections - 35 USC § 102
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.
(I) Claims 1, 2, 6, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iavarone et al. (US 2007/0041944, Feb. 22, 2007, hereinafter referred to as Iavarone ‘944).
With regard to structural limitations “a method comprising reducing the amount (or expression level) of ID2 protein in a subject having a tumor (or glioblastoma or prostate cancer, elected)” (claims 1, 2, 6, and 11):
Iavarone ‘944 disclosed a method for treating cancer or for inhibiting proliferation of a cancer or tumor cell comprising administering to a subject a protein or other agent that sequesters an Id protein(s) in the cytoplasm of the tumor or cancer cell.
PNG
media_image1.png
200
400
media_image1.png
Greyscale
. The cancers include prostate cancer; nervous system tumors. The central nervous system tumor can include, cerebellar astrocytoma, medulloblastoma, ependymona, brain stem glioma, optic nerve glioma, or germinoma. Expression of ENH in three human neuroectodermal cell lines, the glioma cell line SF188 (= glioblastoma) and the neuroblastoma cell lines IMR-32 and SK-NSH (SH-N or SH-F) markedly inhibited colony formation. Retinoic acid (RA) induced progressive elevation of ENH mRNA and protein in neuroblastoma SH-N and SH-F cells, suggesting that ENH may play a role in multiple differentiation pathways in the nervous system. Higher concentrations of RA led to marked inhibition of N-myc and Id2 gene expression in N-myc-amplified neuroblastoma cells. A late decrease of Id2 protein was evident in RA-treated SH-N cells (page 36/50, [0105]; page 39/50, [0138]; page 38/50, [0130]).
Thus, these teachings of Iavarone ‘944 anticipate Applicant’s claims 1, 2, 6, and 11.
(II) Claims 1, 2, 6, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wallrapp et al. (WO 2018/175924, September 27, 2018, hereinafter referred to as Wallrapp ‘924).
With regard to structural limitations “a method comprising reducing the amount (or expression level) of one or more proteins selected from the group consisting of NR4A1 and KLF4 in a subject having a tumor (or glioblastoma, renal clear cells carcinoma, bladder cancer, or prostate cancer, elected)” (claims 1, 2, 6, and 11):
Wallrapp ‘924 disclosed a method for treating a disease by induction of an innate lymphoid cell (ILC) Type 2 inflammatory response comprising administering to a subject in need thereof a therapeutically effective amount of an agent capable of reducing the expression or inhibiting the activity of one or more genes or polypeptides selected from the group consisting of Nmur1, Dgat2, Calca, Ccl5, Btgl, Nr4a1, Klf3, Klf4, Csf2, Stab2, Sdc4, Ccr2, Fosb, Zfp3611, Lpcat2 and Ltb. The disease may be cancer. The agent may comprise a therapeutic antibody, antibody fragment, antibody-like protein scaffold, aptamer, nucleic acid molecule, protein or small molecule. Examples of solid tumors include prostate cancer, liver and bile duct carcinoma, embryonal carcinoma, kidney cancer (e.g., renal cell carcinoma, clear cell carcinoma, Wilm's tumor, nephroblastoma), bladder carcinoma, esophageal carcinoma (e.g., esophageal adenocarcinoma), tumors of the brain ( e.g., glioma, glioblastoma, medullablastoma) (page 4, [0012]; page 6, [0014 and 0015]; pages 63 to 64, [0123]).
Thus, these teachings of Wallrapp ‘924 anticipate Applicant’s claims 1, 2, 6, and 11 because the method recites open-ended transitional phrase “comprising”.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YIH-HORNG SHIAO whose telephone number is (571)272-7135. The examiner can normally be reached Mon-Thur, 08:30 am to 07:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at 571-272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
Prosecution Insights