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 .
Status of the Claims
Claims 1-20 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/28/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Restriction/Election Requirement
Applicant's election with traverse of Group I in the reply filed on 12/09/2025 is acknowledged. The traversal is on the grounds that the prior art used to break unity of invention falls under the prior art exception under 35 U.S.C. 102(b)(2)(A). Applicant has provided a declaration under 37 C.F.R. 1.130(a) showing that the subject matter was obtained directly from the inventor.
Therefore, the requirement for restriction/election requirement is withdrawn in whole, and Groups II and III have been reinstated. Examination will include the full scope of the claims.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 reads that “…Y is C or N;…” and should read “…Y is CH or N;…”.
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 11-20 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 conferring anti-cancer activity to and modulating mitochondrial function of a leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, or breast cancer cell, does not reasonably provide enablement for conferring anti-cancer activity to any cancer cell or modulating mitochondrial function of any cell comprising administering a compound of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of conferring anti-cancer activity to a cancer cell, and modulating mitochondrial function in a cell, comprising administering a compound of claim 1.
Nature of the invention
The nature of the invention is performance of a method of conferring anti-cancer activity to a cancer cell, and modulating mitochondrial function in a cell, comprising administering a compound of claim 1. It is taught that the anti-cancer activity results in the inhibition of proliferation, the inhibition of metastasis, and/or the killing of the cancer cell.
State of the prior art
Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of proliferative diseases, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in almost every part of the body. For example, leukemia is any malignant neoplasm of the blood-forming tissues. Leukemia can arise from many different sources. These include viruses such as EBV, which causes Burkitt's lymphoma, and HTLV -1, linked to certain T cell leukemias. Others are linked to genetic disorders, such as Fanconi's anemia, which is a familial disorder, and Down's syndrome. Other leukemias are caused by exposure to carcinogens such as benzene, and some are actually caused by treatment with other neoplastic agents. Still other leukemias arise from ionizing radiation, and many are idiopathic. Leukemias also differ greatly in the morphology, degree of differentiation, body location (e.g., bone marrow, lymphoid organs, etc.) There are many types of leukemias. There are B -Cell Neoplasms such as B-cell prolymphocytic leukemia and Hairy cell leukemia. There are T-Cell Neoplasms such as T-cell prolymphocytic leukemia, aggressive NK cell leukemia, adult T cell leukemia/lymphoma (ATLL), and T-cell granular Lymphocytic leukemia.
There are different kinds of acute myeloid leukemias (undifferentiated AML, acute myeloblastic, acute myelomonocytic leukemia, acute monocytic leukemias, acute monoblastic, acute megakaryoblastic (AmegL), acute promyelocytic leukemia (APL), and erythroleukemia). There is also lymphoblastic leukemia, hypocellular acute myeloid leukemia, Ph-/BCR- myeloid leukemia, and acute basophilic leukemia. Chronic leukemias include chronic lymphocytic leukemia (CLL, which exists in a B-cell and a T-cell type), prolymphocytic leukemia (PLL), large granular lymphocytic leukemia (LGLL, which goes under several other names as well), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL), and many others.
The nature of the invention and predictability in the art, with specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] ...anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
No single drug or compound has been discovered that is effective in conferring anti-cancer activity to every type of cancer. See In re Hokum, 226 USPQ 353 (ComrPats 1985).
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of conferring anti-cancer activity to a cell and modulating mitochondrial function of a cell, comprising administering a compound of claim 1, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of conferring anti-cancer activity to a cell and modulating mitochondrial function of a cell, comprising administering a compound of claim 1.
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of conferring anti-cancer activity to a cell and modulating mitochondrial function of a cell, comprising administering a compound of claim 1.
Similarly, according to the claims, compounds of claim 1 are capable of effectively inhibiting the proliferation of or killing any cancer cell.
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification only provides examples for inhibiting proliferation of leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer cells comprising administering compounds of claim 1. There is insufficient disclosure to reasonably conclude that the method of conferring anti-cancer activity to any cancer cell or modulating mitochondrial function of any cell, comprising administering a compound of claim 1, as recited, would contribute to inhibiting of proliferation of any cancer cell. It is also shown, in Figures 10A-C, that the compounds were not able to inhibit proliferation of every type of cancer cell that was tested. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which of the infinite number of compounds of claim 1 would be capable of conferring anti-cancer activity and modulating mitochondrial activity to which types of cancer cells. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of conferring anti-cancer activity to any cancer cell and modulating mitochondrial function of any cell, comprising administering a compound of claim 1, is clearly justified.
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 1-3 and 10-20 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 1-3, the phrases “targeting ligand” and “affinity tag” render the claims indefinite because the claims include elements not actually disclosed. The specification, on page 12, defines a “targeting ligand” as “well known to those of ordinary skill in the art, with examples including, but not limited to folic acid, mannose, an antibody (e.g., anti-CD22, anti-CD25, anti-EpCAM, etc.), an aptamer (e.g., SYL3C for targeting EpCAM, AptA for targeting Mucin1, etc.), or a polypeptide (e.g., arginine-glycine- aspartic acid (RGD) motif, yclic 9-mer iRGD (CRGDKGPDC), other polypeptides targeting integrins, epidermal growth factor receptor (EGFR), somatostatin receptors (SSTRs), gonadotropin-releasing hormone receptor (GnRH-R), bombesin (Bn) receptors, G protein- coupled receptors (GPCRs), etc.)”. “Affinity tags” are defined in the specification, on pages 12-13, as “well known to those of ordinary skill with examples including, but not limited to, polyhistidine tag, glutathione-S-transferase (GST) tag, Strep-tag (streptavidin-binding tag), almodulin-binding peptide (CBP) tag, chitin-binding domain (CBD), FLAG tag, HA tag, c-Myc tag, etc.”.
Therefore, non-limiting examples are provided for both “targeting ligands” and “affinity tags”, which results in an indefinite number of compounds that would fall under claims 1-3. Claims 10-20 are rejected as being dependent upon a rejected claim and failing to clarify the targeting ligand or affinity tag structure. This rejection would be overcome by including specific targeting ligands or affinity tags to be used in the invention.
Claim 20 recites the limitation "The method of claim 43". There is insufficient antecedent basis for this limitation in the claim, since claim 43 does not exist.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8 and 9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 requires that the compound is bound to chlorine. Claim 1 also requires that R1 and R2 are selected from
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. The compounds of claims 8 and 9, which are dependent upon claim 1, do not contain these features. Therefore, claim 8 and 9 fail to include the limitations of the claim upon which they depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Nonstatutory 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, 5, 10, 16, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40 and 42 of copending Application No. 18/006,889 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Application ‘889 teaches, in claim 40, a method of increasing mitochondrial respiration in a cell comprising contacting the cell with a compound of formula (II). This compound/method reads on instant claims 1, 5, 10, and 16. It is taught, in claim 42, that the cell is in a subject, as in instant claim 19.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Advisory Notice
Claims 4, 6, and 7 appear allowable if rewritten in independent form.
Conclusion
Claims 1-3, 5, and 8-20 are rejected.
Claims 4, 6, and 7 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624