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 .
This action is in response to the amendment, filed 10/29/2025, in which claims 14-15 were cancelled.
Priority
Application filling date 03/29/2022 is acknowledged.
Rejections withdrawn
The rejection of claims 1-3, 10, 12, 14, under 35 U.S 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, has been withdrawn in view of Applicant’s arguments to the claims in the reply in the reply filed 10/29/2025.
The rejection of claims 24, under 35 U.S 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, has been withdrawn in view of Applicant’s arguments to the claims in the reply in the reply filed 10/29/2025.
The rejection of claim 14, under 35 U.S 102(a)(1), is moot in view of Applicant’s cancellation of the claim in the reply in the reply filed 10/29/2025.
The rejection of claim 15, under 35 U.S 103, is moot in view of Applicant’s cancellation of the claim in the reply in the reply filed 10/29/2025.
Maintained 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 22-23 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.
This rejection was made in the Office action mailed 04/29/2025 and has been rewritten to address the arguments in the reply filed 10/29/2025.
The claims recite a method for treating cancer comprising providing to the subject a therapeutically effective amount of the therapeutic agent comprising a miRNA conjugated to a targeting element. The critical agent is a functional therapeutic agent; however, the claim is not limited to any particular type of cancer. The claim relies on a functional limitation “treating cancer in a subject with a therapeutically effective amount of the agent”, without providing structural or operational details to determine how the treating is achieved.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions methods and compositions for targeted delivery of microRNA modulators (e.g., miRNA agomirs and antagomirs) to Ovarian Cancer cells and their tumor microenvironment. (e.g., paragraph 0014). The specification envisions targeting elements (e.g. folic acid, fatty acids or peptides) which bind to the Ovarian Cancer cells surface receptor FOLR1 and/or the adipocyte cells surface receptors FAT and FABP4; and carrier or delivery nanoparticles that can deliver therapeutic agents to targeted Ovarian Cancer cells and adipocytes to enhance their intra-cellular penetration while protecting them from degradation (e.g., paragraph 0015). The specification envisions compositions that employ such therapeutic agents, targeting elements, and/or carrier or delivery nanoparticles can be used in methods employing local subcutaneous (e.g., injection, patch or microneedles) or intra-peritoneal administration of the therapeutic agents to the human Ovarian Cancer cells and their tumor microenvironment.
The examples, do not teach treating subjects with any type of cancer; furthermore, the specification does not provide working examples, data or evidence demonstrating that the claimed invention actually treats subjects with cancer. Thus, it is impossible for one to extrapolate from the examples, that would necessarily meet the structural/functional characteristics of treating cancer, there is no guidance of which microRNA to be used.
While the specification discloses a method for treating ovarian cancer, this example is not representative of the diverse pathologies included in the term “cancer”.
Therefore, the skilled artisan would have reasonable concluded applicants were not in possession of the intended claimed invention for claims 22-23.
Claims 22-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because specification does not reasonably provide enablement for “a method for treating cancer in a subject”. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims.
This rejection was made in the Office action mailed 04/29/2025 and has been rewritten to address the arguments in the reply filed 10/29/2025
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404: Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. 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 instant claim 22 is drawn to a method for treating cancer comprising providing to the subject a therapeutically effective amount of the therapeutic agent of claim 1. Claim 23 limits wherein providing the therapeutic agents is provided subcutaneously, transcutaneously, intraperitoneally, or intravenously. The nature of the claim is complicated, because the claim requires the outcome of “treating a cancer in a subject”, yet the claim is drawn to administering a therapeutic agent as the only step to treat any cancer.
Breadth of the claim: The claim is exceptionally broad. It encompass the use of a therapeutic agent comprising a miRNA to treat distinct types of cancer. The specification does not provide working examples, data or evidence demonstrating the claimed invention that actually treat any cancer, except ovarian cancer. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The specification envisions methods and compositions for targeted delivery of microRNA modulators (e.g., miRNA agomirs and antagomirs) to Ovarian Cancer cells and their tumor microenvironment. (e.g., paragraph 0014). The specification envisions targeting elements (e.g. folic acid, fatty acids or peptides) which bind to the Ovarian Cancer cells surface receptor FOLR1 and/or the adipocyte cells surface receptors FAT and FABP4; and carrier or delivery nanoparticles that can deliver therapeutic agents to targeted Ovarian Cancer cells and adipocytes to enhance their intra-cellular penetration while protecting them from degradation (e.g., paragraph 0015). The specification envisions compositions that employ such therapeutic agents, targeting elements, and/or carrier or delivery nanoparticles can be used in methods employing local subcutaneous (e.g., injection, patch or microneedles) or intra-peritoneal administration of the therapeutic agents to the human Ovarian Cancer cells and their tumor microenvironment. This strategy results in minimizing systemic exposure and "off target" effects, further improving therapeutic index, reducing cost of goods, and improving patients' convenience and adherence to treatment (e.g., paragraph 0016).
The examples, do not teach treating subjects with ovarian cancer; furthermore, the specification does not provide working examples, data or evidence demonstrating that the claimed invention actually treats subjects with cancer.
Predictability and state of the art: The state of the art with respect to using microRNA conjugated with targeting molecules for treatment of cancer is under developed and unpredictable. Nishimura et al. (Cancer Discovery, 2013) teaches dual targeting targeted the expression of EphA2, an oncogenic protein expressed in ovarian cancer, using siRNA and miR-520d-3p resulted in robust depletion of the protein levels. MicroRNA have a relevant role in the field of tumor research, showing potential as excellent biological targets for early screening, targeted therapy, drug resistance monitoring and prognosis improvement in ovarian cancer. However, given its substantial variability and complex biological effects, the specific mechanism of miRNAs in tumors of different tissue types remains largely unclear (Zhao et al., Reproductive Science, 2022); (Krasniqi et al., Biomarker Research, 2021); (Imran et al. Cell Communication and Signaling, 2023); (Davies et al. Genes 2022).
Thus, the teachings of the post-filing art are consistent with the prior art demonstrating the underdeveloped and unpredictable nature of the invention.
Amount of experimentation necessary: Cancer disease is highly complex and gene-based therapies are still in developmental stages. It would require a large amount of experimentation to make use of microRNA for treatment of cancer disease. For a specific gene therapy to be efficacious in cancer disease, it would require to address: (1) the specific means of microRNA delivery, activity, (2) to define the specific dosage of therapeutic molecules (microRNA-conjugated to targeting molecules carried by nanoparticles) delivered to the cells or to the subjects in time course, (3) the potential deleterious effect on normal cells and tissues.
In view as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 22-23 are not considered to be enabled by the instant disclosure.
In view of the breadth of the claims, the lack of guidance provided by the specification, the lack of the predictability of the art to which the invention pertains, undue amount of experimentation would be required to make and use the claimed invention to treat ovarian cancer in a subject, with a reasonable expectation of success. Because the specification does not contain a detailed description of how to make and use the method based on administration of pharmaceutical composition comprising the claimed therapeutic agent comprising a microRNA-conjugated to a targeting molecules, according to the invention, and absent working examples that provide evidence that is reasonably predictive of the ability of treat cancer in subjects, the claims are not enabled commensurate in scope with the claimed invention.
While the specification discloses a method for treating ovarian cancer, this example is not representative of the diverse pathologies included in the term “cancer”.
Maintained 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.
Claims 1-2, 5-6, 10, 16, 19-20, 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lieberman et al. (“Lieberman”, US 11,147,828 B2, published October 2021).
This rejection was made in the Office action mailed 04/29/2025 and has been rewritten to address the amendments and arguments in the reply filed 10/29/2025.
Regarding claims 1-2, Lieberman teaches methods to treat cancers by targeting cancer cells with a plurality of different miRNA and/or miRNA mimetics to increase the levels of more than one miRNA that are reduced or lacking in the cancer stem cells compared with non-stem cell cancer
cells (e.g., paragraph 3rd, column 12). Lieberman teaches that cancers can be treated by targeting the cancer stem cell with any one or a combination of the following miRNAs and mimetics thereof: miR-107; 20 miR-l0a; miR-128a; miR128b; miR-132; miR-138; miR-16; miR-17; miR-195; miR-199a; miR-20; miR-200a; miR-200b; miR-200c; miR-20b and miR-22 (e.g., paragraph 2nd, column 12). Lieberman teaches that the cancers which can be treated by the methods and compositions as disclosed include bladder cancer; breast cancer; ovarian cancer including those arising from epithelial cells, stromal cells, germ cells and mesenchymal cells (e.g., paragraph 3rd, column 60). Lieberman teaches term "targeting" as used herein in the context of "targeting a cancer cell" means directing a therapeutic agent as disclosed herein, such as a let-7 miRNA or homologues thereof to that cancer cell to treat a cancer comprising such a cancer stem cell (e.g., paragraph 2nd, column 27). Lieberman teaches that "target cell" as used herein refers to a cell which comprises cell surface antigens, such as for example but not limited to, cell surface receptors or glycoprotein or other cell surface markers which the targeting moiety as disclosed; examples of a targeting moiety include, but are not limited to, an antibody, an antigen binding fragment of an antibody, an antigen, a ligand, a receptor, one member of a specific binding pair, a polyamide including a peptide having affinity for a biological receptor, an oligosaccharide. Targeting moiety useful in the methods and compositions as disclosed herein binds to cell-surface antigens or proteins present on cancer stem cells. Examples include, but are not limited to, tumor-associated antigens (TAAs), the HLA-DR antigen, c-erbB-2 proto-oncogene, cancer antigen 125 45 (CA 125, human ovarian cancer cell surface antigen (it reads on ovarian cancer cell marker) ( (e.g., paragraph 5th, column 27).
It is noted that, Liberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity.
Regarding claim 5, Lieberman teaches that the let-7 miRNA (therapeutic agent) or let-7 agent can further comprise a binding moiety (it reads on linker) and a targeting moiety, and in some embodiments the binding moiety binds let-7 miRNA to the targeting moiety (e.g., paragraph 3rd, column 3). Targeting moiety useful in the methods and compositions as disclosed herein binds to cell-surface antigens or proteins present on cancer stem cells. Examples include, but are not limited to, tumor-associated antigens (TAAs), the HLA-DR antigen, c-erbB-2 proto-oncogene, cancer antigen 125 (CA 125, human ovarian cancer cell surface antigen (it reads on ovarian cancer cell target marker) ( (e.g., paragraph 5th, column 27).
Regarding claim 6, Lieberman teaches that a mature miRNA is a single-stranded RNA molecule of about 21-23 nucleotides in length which is complementary to a target sequence (e.g., paragraph 1st, column 16).
Regarding claims 10, Lieberman teaches targeting moiety include, but are not limited to, an antibody, an antigen binding fragment of an antibody, an antigen, a ligand, a receptor, one member of a specific binding pair, a polyamide including a peptide having affinity for a biological receptor, an oligosaccharide (e.g., paragraph 5th, column 27).
Regarding claim 16, 19 Lieberman teaches binding moiety (linker) useful in the methods as disclosed herein is a protein or a nucleic acid binding domain of a protein, and in some embodiments the binding moiety is fused to the carboxyl terminus of the targeting moiety, and in some embodiments, the binding moiety is the protein protamine or nucleic acid binding fragment of protamine (e.g., paragraph 3rd, column 3).
Regarding claim 20, Lieberman teaches methods of the present invention to also encompass delivery of let-7 miRNA (it reads on therapeutic agent) and/or let-7 mimetics, either alone or complexed to targeting moieties orally in granular form including sprayed dried particles, or complexed to form micro or nanoparticles (e.g., paragraph 1st, column 51).
Regarding claims 22, Lieberman teaches method of treating and/or preventing cancer comprising targeting cancer stem cells by administering miRNAs which have reduced expression or are lacking in the cancer stem cells (e.g., abstract). Lieberman teaches that "therapeutically effective amount" as used herein, e.g., of a miRNA-related composition as disclosed herein means a sufficient amount of the composition to treat a disorder, at a reasonable benefit/risk ratio applicable to any medical treatment (e.g., paragraph 4th, column 28, lane 62).
Regarding claim 23, Lieberman teaches pharmaceutical compositions are useful of for the treatment or prevention of cancer in a subject (e.g., paragraph 3rd, column 7). Lieberman teaches parenteral administration" and "administered parenterally" as used herein mean modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intraventricular, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular (e.g., paragraph 3rd, column 30, lane 21).
Regarding claim 24, Lieberman teaches that the cancers which can be treated by the methods and compositions as disclosed include bladder cancer; breast cancer; ovarian cancer including those arising from epithelial cells, stromal cells, germ cells and mesenchymal cells (e.g., paragraph 3rd, column 60).
Maintained 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Lieberman et al. (“Lieberman”, US 11,147,828 B2, published October 2021) in view of Dai et al. (“Dai”, Journal of Ovarian Research, 2020).
As noted in the anticipation rejection above Lieberman anticipates claims 1-2, 5-6, 10, 16, 19-20, 22-24 and so in anticipating these claims, said claims are also considered obvious under 35 USC 103(a) over Dai for the reasons set forth below ("lack of novelty is the epitome of obviousness" May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))).
This rejection was made in the Office action mailed 04/29/2025 and has been rewritten to address the amendments and arguments in the reply filed 10/29/2025.
Lieberman does not teach a cell of the ovarian cancer tumor microenvironment is an adipocyte as is required by instant claims 3-4. However, this is cured by Dai.
Regarding claim 3-4, Dai teaches growth and metastasis of epithelial ovarian cancer (EOC) are closely related to the surrounding microenvironment. The cells, such as adipocyte, in the tumor microenvironment contribute to the metastasis, growth and angiogenesis of ovarian cancer (e.g., paragraph 2nd, column right, page 2). Dai teaches that since adipocytes play important roles in the growth, metastasis and
angiogenesis of epithelial ovarian cancer, therapeutic interventions target or regulate adipocytes might be effective strategy of epithelial ovarian cancer treatment (e.g., paragraph 3rd, column left, page 7).
Lieberman and Dai both directed to study ovarian cancer. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to deliver nanoparticles carrying a microRNA therapeutic agent that further comprise a binding moiety and a targeting moiety, where the targeting moiety binds to cell-surface antigens on cancer stem cells, such as human ovarian cancer cell surface antigen CA125 as taught by Lieberman and target adipocytes present in the ovarian tumor microenvironment as taught by Dai; for someone skilled in the art would have been obvious to use both teachings to achieve the predictable result of obtaining a composition suitable for treating or preventing ovarian cancer by targeting adipocytes in the ovarian tumor microenvironment using a miRNA.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to target adipocytes present in the ovarian tumor microenvironment, since adipocytes promote ovarian cancer progression, therefore adipocytes would be part of the anticancer strategy for treatment of patients with ovarian cancer to improve their quality of life using nanoparticles carrying microRNA as a therapeutic agent.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 7, 12-13, 20- 21 are rejected under 35 U.S.C. 103 as being unpatentable over Lieberman et al. (“Lieberman”, US 11,147,828 B2, published October 2021), and Dai et al. (“Dai”, Journal of Ovarian Research, 2020) as applied to claims 1-6, 10, 16, 19-20, 22-24 above, and further in view of Thibonnier et al. (“Thibonnier”, WO 2017/187426 A1, cited as reference B2 in IDS filed 03/29/2022).
Lieberman and Dai does not teach the antagomir or agomir as required by instant claim 7. Lieberman and Dai do not teach, the targeting element fatty acid and Fatty Acid Translocase (FAT/CD36/SCARB3) and/or the fatty Acid Binding Protein 4 (FABP4) transporters, as required by instant claims, 12-13. Lieberman and Dai does not teach the therapeutic agent encapsulated within a lipid nanoparticle, as required by instant claim 20. Lieberman and Dai does not teach a therapeutic agent associated with liposome as required by instant claim 21. However, this is cured by Thibonnier.
Regarding claim 7, Thibonnier teaches a miRNA inhibitor that provides upstream control of a variety of proteins involved in metabolism and thermogenesis (e.g., paragraph 0006). Thibonnier teaches that the terms "antagonist", "inhibitor" and "antagomir" are used interchangeably (e.g., paragraph 0018).
Regarding claim 12, Thibonnier teaches that the therapeutic agent is a nucleic acid (Oligonucleotide Therapeutic, ONT), a gene editing agent, a polypeptide, or a small molecule. In some embodiments, the nucleic acid is a miRNA (e.g., paragraph 0009). Thibonnier teaches method of inhibiting mir-22 in a cell comprises administering to the cell a mir-22 antagonist, a molecule comprising a therapeutic agent conjugated to a fatty acid, a liposome comprising phospholipids, cholesterol, and a therapeutic agent, or a nanoparticle containing a therapeutic agent. The cell may be an adipocyte, pre-adipocyte, fibroblast, or vascular endothelial cell (e.g., paragraph 0008). Thibonnier teaches synthesis and validation of a series of miRNA analogs that are covalently attached to fatty acids to facilitate preferential targeting to adipocyte Fatty Acid Translocase (FAT) or CD36; by coupling miRNAs to a fatty acid leads to the selective active transport through FAT present on adipocyte surfaces, chimeras (AdipomiRs) made of single stranded miRNAs conjugated to fatty acids can be synthesized (e.g., paragraph 238).
Regarding claim 13, Thibonnier teaches that the target cell may be an adipocyte precursor such as a pre-adipocyte or adipose tissue mesenchymal stem cell (ATMSC). ATMSCs possess the ability to differentiate into multiple lineages, such as adipocytes, osteocytes, and chondrocytes and are present in human subcutaneous adipose tissue in appreciable quantities (e.g., paragraph 0117). Thibonnier teaches that bind to an adipose target cell comprising one or more ATMSC-positive surface markers. Exemplary ATMSC positive surface markers include CD9 (tetraspan), CDlO (MME), CD13 (ANPEP), CD29 (B-1 integrin), CD36 (FAT) (e.g., paragraph 0118). Thibonnier teaches that examples of white adipose tissue-positive markers include adiponectin, caveolin-1, caveolin-2, CD36 (FAT), CLH-22 (clathrin heavy chain chr. 22), FABP4 (adipocyte protein 2, ap2), SLC27Al (FATPl), SLC27A2 (FATP2), GLUT4 (glucose transporter 4) (e.g., paragraph 0119).
Regarding claim 20, Thibonnier teaches that nanoparticle delivery of a therapeutic agent ( e.g., a compound of the disclosure, nucleic acid, genetic editing agent, polypeptide, or small molecule) to an adipocyte by combination of the therapeutic agent to nanoparticles (e.g., paragraph 0109).
Regarding claim 21, Thibonnier teaches using the fatty acid conjugated miRNAs (AdipomiRs) to help anchor the thermogenic miRNA analogs (compounds of the disclosure) onto the SDC liposome membrane surfaces (e.g., paragraph 0245).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to couple microRNA therapeutic agent that further comprise a binding moiety and a targeting moiety taught by Lieberman, to target adipocytes present in the ovarian tumor microenvironment as taught by Dai with a the therapeutic agent miRNA that are covalently attached to fatty acids to facilitate preferential targeting to adipocyte Fatty Acid Translocase (FAT) or CD36 and a liposome containing a therapeutic agent taught by Thibonnier; for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a composition suitable for treating ovarian cancer by targeting adipocytes with a therapeutic agent miRNA covalently attached to fatty acids to facilitate preferential targeting to adipocyte Fatty Acid Translocase (FAT) or CD36.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to use the therapeutic agent miRNA covalently attached to fatty acid to target CD36 or FABP4 transporters expressed in adipocytes present in the ovarian tumor microenvironment, since adipocytes promote ovarian cancer progression, therefore adipocytes would be part of the anticancer strategy for treatment of patients with ovarian cancer to improve their quality of life.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 8-9, 11 are rejected under 35 U.S.C. 103 as being unpatentable over Lieberman et al. (“Lieberman”, US 11,147,828 B2, published October 2021) as applied to claims 1-2, 5-6, 10, 16, 19-20, 22-24 above, and further in view of Zhao et al. (“Zhao”, Expert Opin. Drug Deliv. 2008).
Lieberman does not teach folic acid and folic receptor alpha as required by instant claims 8-9, 11. However, this is cured by Zhao.
Regarding claims 8-9, 11, Zhao teaches that conjugates of folic acid and anti-folate receptors antibodies (peptide bind to folic receptor) can be taken up by cancer cells via receptor-mediated endocytosis, thus providing a mechanism for targeted delivery to folate receptors positive cells (e.g., abstract). Zhao teaches folate receptor-alpha is consistently expressed in several carcinomas, especially in non-mucinous ovarian carcinomas, uterine carcinomas, testicular choriocarcinomas, ependymomas, and pleural mesotheliomas (e.g., paragraph 4th, column 1, page 310). Zhao teaches folate conjugated oligodeoxyribonucleotides (ODNs) to facilitate targeted delivery to tumor cells (e.g., paragraph 2nd, column 1, page 312).
Lieberman and Zhao are directed to treatment of ovarian cancer. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to conjugate the miRNA therapeutic agent taught by Lieberman, with the folate conjugated oligodeoxyribonucleotides (ODNs) to facilitate targeted delivery to tumor cells to target folate receptor-expressing ovarian cancer cells taught by Zhao; for someone skilled in the art would have been obvious to use both teachings to achieve the predictable result of obtaining a composition of miRNA-folic acid conjugate or an anti-folate receptor antibody suitable for targeting folate receptors expressed in ovarian cancer cells.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to conjugate a therapeutically relevant miRNA directly to a targeting ligand (folic acid) whose receptor is overexpressed on cancerous cells such as folate receptors in ovarian cancer cells as a therapeutic anticancer drug for treatment to improve the quality of life of patients with ovarian cancer.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Lieberman et al. (“Lieberman”, US 11,147,828 B2, published October 2021) and Zhao et al. (“Zhao”, Expert Opin. Drug Deliv. 2008) as applied to claims 1-2, 5-6, 8-11, 16, 19-20, 22-24 above, and further in view of Orellana et al. (“Orellana”, Sci. Transl. Med. 2017).
Lieberman and Zhao do not teach linker is cleavable/ non-cleavable as is required by instant claims 17-18. However, this is cured by Orellana.
Regarding claims 17-18, Orellana teaches tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative
breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics (e.g., abstract) . Orellana teaches conjugating a drug to a ligand, a cleavable bridge is desired for delivery of therapeutic cargo because release of the unmodified cytotoxic agent is often required for maximal drug efficacy (e.g., paragraph 3rd, column 1, page 2). Orellana teaches method that relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor (e.g., abstract). Orellana teaches the 5’ end of a modified passenger strand of miR-34a (miR-34a-3p) was conjugated to folate-dibenzocyclooctyne (Fol-DBCO) using an unreleasable conformation (folate–miR-34a-3p: Fol-34a-3p) or a releasable conformation (folate–SS-miR-34a-3p: Fol-SS-34a-3p) which contains a reducible disulfide linkage (SS) between the miRNA and the folate molecule (e.g., paragraph 3rd, column 1, page 2; Fig 1A; Fig. S2A). Orellana teaches that the releasable and unreleasable FolamiRs efficiently entered the cell and retained activity, suggesting that the release of folate ligand from Folamir is not necessary for miRNA activity (e.g., paragraph 2nd, column 2, page 2; Fig. 2). Orellana teaches that inclusion of an intermolecular endosomal escape mechanism incorporated into second-generation FolamiRs (folate-dibenzocyclooctyne) could ensure robust cytosolic delivery of the therapeutic miRNAs (e.g., paragraph 1st, page 7).
Lieberman, Zhao and Orellana are directed to treatment of cancer. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Lieberman -the therapeutic agent miRNA with the teachings of Zhao -the folate conjugated oligodeoxyribonucleotides (ODNs) to facilitate targeted delivery to tumor cells to target folate receptor-expressing ovarian cancer cells taught by Zhao, and with the method that relies on direct attachment of microRNAs to folate (FolamiR), releasable and unreleasable FolamiRs which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor to target folate receptor-expressing cancer cells taught by Orellana; for someone skilled in the art would have been obvious to use both teachings to achieve the predictable result of obtaining a composition of miRNA- folate-dibenzocyclooctyne releasable and unreleasable FolamiRs conjugate suitable for targeting folate receptors expressed in ovarian cancer cells and be releasable to avoid endosomal entrapment of the miRNA.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to conjugate a therapeutically relevant miRNA directly to a targeting ligand releasable and unreleasable FolamiRs conjugate whose receptor is overexpressed on cancerous cells such as folate receptors in ovarian cancer cells as a therapeutic anticancer drug and be releasable in cytoplasm of ovarian cancer cells.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicant’s arguments
Response to Arguments on the Grounds of 35 U.S.C 112(a).
With respect to the claim 22-23 is rejected under Grounds of 35 U.S.C 112(a), Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “the method of use of the therapeutic is also enabled, at least because the Specification provides clearly defined methods of use for the claimed therapeutic. For example, the specification establishes that "[t]he Folate receptor alpha (FOLR1) is a cell surface glycophosphatidylinositol (GPI)-anchored protein with a high affinity for its ligand folic acid [25]. FOLR1 is highly expressed in malignant cells, especially the Ovarian Cancer cells (FIG. 3)." ([0015]). The specification also states that "disclosed herein is a method of modulating genes expression (and consequently, in some embodiments, protein expression) in a subject comprising administering to the subject any of the compositions described above. In some embodiments, providing the composition or therapeutic agent comprises injecting the composition or therapeutic agent subcutaneously, transcutaneously, intraperitoneally or intravenously (0039)”.
However, while the specification discloses a method for treating ovarian cancer, this example is not representative of the diverse pathologies included in the term “cancer”. The specification does not provide working examples, data or evidence demonstrating that the claimed invention actually treats subjects with cancer.
Response to Arguments on the Grounds of 35 U.S.C 102(a)(1).
With respect to the claims 1-2, 5-6, 10, 16, 19-20, 22-24 is rejected under Grounds of 35 U.S.C 102(a)(1), Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “that Lieberman does not clearly and unambiguously disclose, in a single embodiment, the presently claimed therapeutic agent comprising (i) a miRNA oligonucleotide therapeutic conjugated to (ii) a "targeting element that binds to an ovarian cancer cell or a cell of an ovarian cancer tumor microenvironment," as required by claim 1. At best, Lieberman's exemplified conjugates target CD44+ breast cancer stem cells and provide only generic, laundry-list statements about "targeting moieties" and a broad catalog of cancers. Applicant submits that it is improper to construct a rejection alleging anticipation based on picking and choosing from unrelated lists to reconstruct the therapeutic agent and the associated limitations of claim 1. Furthermore, Lieberman does not disclose any targeting element that binds a cell of the ovarian tumor microenvironment, as recited in claim 1. Applicant submits that Lieberman's generalized teachings and lists do not teach each and every limitation of claim 1”.
However, Lieberman teaches methods to treat cancers by targeting cancer cells with a plurality of different miRNA and/or miRNA mimetics (e.g., paragraph 3rd, column 12). Lieberman further teaches that cancers can be treated by targeting the cancer stem cell with any one or a combination of the following miRNAs and mimetics thereof: miR-107; 20 miR-l0a; miR-128a; miR128b; miR-132; miR-138; miR-16; miR-17; miR-195; miR-199a; miR-20; miR-200a; miR-200b; miR-200c; miR-20b and miR-22 (e.g., paragraph 2nd, column 12). Lieberman teaches that the therapeutic agent let-7 miRNA agent can further comprise a binding moiety (it reads on linker) and a targeting moiety (e.g., paragraph 3rd, column 3). Liberman teaches examples of a targeting moiety include, but are not limited to, an antibody, an antigen binding fragment of an antibody, an antigen, a ligand, a receptor, one member of a specific binding pair, a polyamide including a peptide having affinity for a biological receptor, an oligosaccharide. Furthermore, Lieberman teaches that targeting moiety binds to cell-surface antigens or proteins present on cancer stem cells. Examples include, but are not limited to, tumor-associated antigens (TAAs), cancer antigen 125 (CA 125, human ovarian cancer cell surface antigen, as an example for a target on ovarian cancer cells (e.g., paragraph 5th, column 27).
A Prior Art reference anticipates or renders obvious a claim when it clearly and unequivocally describes the claimed limitations arranged as in the claim, or when it would have been obvious to combine disclosed elements within the reference. Liberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity.
Accordingly, Lieberman either anticipates the claimed agent or at minimum renders the claimed therapeutic agent obvious, as it teaches all the claimed limitations and provides a clear rationale to combine the miRNA therapeutic agent with cancer-cell-targeting elements that bind ovarian cancer.
Response to Arguments on the Grounds of 35 U.S.C 103.
With respect to the claims 3-4 are rejected under Grounds of 35 U.S.C 103, Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “the present claims are not obvious in view of Lieberman alone or in combination with Dai at least because neither reference teaches or suggests a therapeutic agent in which a miRNA oligonucleotide therapeutic is conjugated to a targeting element that binds an ovarian tumor microenvironment cell. At best, Lieberman focuses on let-7 therapy against cancer stem cells (e.g., CD44+ breast models) and relies on generic "targeting moieties," but nowhere discloses or suggests targeting adipocytes in an ovarian tumor microenvironment, a specific targeting ligand for such cells, or the claimed arrangement of a miRNA therapeutic linked to that targeting element. Dai is a review that, at best, may be characterized as describing adipocytes' possible role in ovarian cancer biology and speculating that "therapeutic interventions target or regulate adipocytes might be effective," (Dai, p. 7, spanning columns, emphasis added) but fails to disclose multiple elements recited in the present claims, including, e.g., miRNA-based therapeutic composition, targeting ligand, and linker/delivery. For at least the foregoing reasons, Applicant submits that there is no teaching of Lieberman alone, or in combination with Dai, that would lead one of skill to arrive at the presently claimed therapeutic agent, let alone with any expectation of success”.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Lieberman and Dai teaches the limitations of the claims. Lieberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity. Furthermore, Dai teaches that cells, such as adipocyte, in the tumor microenvironment contribute to the metastasis, growth and angiogenesis of ovarian cancer (e.g., paragraph 2nd, column right, page 2).
Accordingly, a person of ordinary skill in the art would have reasonably understood and been motivated to target adipocytes present in the ovarian tumor microenvironment, since adipocytes promote ovarian cancer progression.
Response to Arguments on the Grounds of 35 U.S.C 103.
With respect to the claims 7, 12-13, 20-21 are rejected under Grounds of 35 U.S.C 103, Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “Lieberman alone or in combination with Dai and/or Thibonnier do not make obvious the present claims. Specifically, Lieberman does not teach or suggest the presently claimed therapeutic agent comprising (i) a miRNA oligonucleotide therapeutic conjugated to (ii) a "targeting element that binds to an ovarian cancer cell" as required by claim 1. Further, Lieberman does not teach or suggest "a cell of an ovarian cancer tumor microenvironment," as acknowledged by the Office Action, and as recited in claim 1. These deficiencies are not remedied by Dai, for at least the reasons set forth above. For example, Dai fails to disclose multiple elements recited in the present claims, including, e.g., miRNA-based therapeutic composition, targeting ligand, and linker/delivery. Similarly, Applicant notes that Thibonnier is silent with respect to ovarian cancer. For at least the reasons set forth above, Applicant submits the present claims are not obvious in view of Lieberman taken alone, or in combination with Dai, Thibonnier, or a combination thereof”.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Lieberman, Dai and Thibonnier teach all the limitations of the claims. Lieberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity. Furthermore, Dai teaches that cells, such as adipocyte, in the tumor microenvironment contribute to the metastasis, growth and angiogenesis of ovarian cancer (e.g., paragraph 2nd, column right, page 2). Additionally, Thibonnier teaches therapeutic agent miRNA that are covalently attached to fatty acids to facilitate preferential targeting to adipocyte Fatty Acid Translocase (FAT) or CD36 and a liposome containing a therapeutic agent.
Accordingly, a person of ordinary skill in the art would have reasonably understood and been motivated to use the therapeutic agent miRNA covalently attached to fatty acid to target CD36 or FABP4 transporters expressed in adipocytes present in the ovarian tumor microenvironment, as part of the anticancer strategy for treatment of patients with ovarian cancer.
Response to Arguments on the Grounds of 35 U.S.C 103.
With respect to the claims 8-9, 11 are rejected under Grounds of 35 U.S.C 103, Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “Lieberman alone or in combination with Dai and/or Thibonnier do not make obvious the present claims. Specifically, Lieberman does not teach or suggest the presently claimed therapeutic agent comprising (i) a miRNA oligonucleotide therapeutic conjugated to (ii) a "targeting element that binds to an ovarian cancer cell" as required by claim 1. Further, Lieberman does not teach or suggest "a cell of an ovarian cancer tumor microenvironment," as acknowledged by the Office Action, and as recited in claim 1. These deficiencies are not remedied by Dai, for at least the reasons set forth above. For example, Dai fails to disclose multiple elements recited in the present claims, including, e.g., miRNA-based therapeutic composition, targeting ligand, and linker/delivery. Similarly, Applicant notes that Thibonnier is silent with respect to ovarian cancer. Applicant submits that Zhao fails to remedy these deficiencies. For example, Applicant notes that Zhao is silent with respect to miRNA oligonucleotide therapeutics, or the tumor microenvironment (as recited in claim 1). For at least the reasons set forth above, Applicant submits the present claims are not obvious in view of Lieberman taken alone, or in combination with Dai, Thibonnier, Zhao, or a combination thereof”.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Lieberman and Zhao teach all the limitations of the claims. Lieberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity. Furthermore, Zhao teaches that conjugates of folic acid and anti-folate receptors antibodies (peptide bind to folic receptor) can be taken up by cancer cells via receptor-mediated endocytosis, thus providing a mechanism for targeted delivery to folate receptors positive cells (e.g., abstract). Zhao teaches folate receptor-alpha is consistently expressed in several carcinomas, especially in non-mucinous ovarian carcinomas, uterine carcinomas, testicular choriocarcinomas, ependymomas, and pleural mesotheliomas (e.g., paragraph 4th, column 1, page 310). Zhao teaches folate conjugated oligodeoxyribonucleotides (ODNs) to facilitate targeted delivery to tumor cells (e.g., paragraph 2nd, column 1, page 312).
Accordingly, a person of ordinary skill in the art would have reasonably understood and been motivated to conjugate a therapeutically relevant miRNA directly to a targeting ligand (folic acid) whose receptor is overexpressed on cancerous cells such as folate receptors in ovarian cancer cells as a therapeutic anticancer drug for treatment of patients with ovarian cancer.
Response to Arguments on the Grounds of 35 U.S.C 103.
With respect to the claims 17-18 are rejected under Grounds of 35 U.S.C 103, Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
The applicant response asserts “Lieberman alone or in combination with Dai, Thibonnier, and/or Zhao do not make obvious the present claims. Specifically, Lieberman does not teach or suggest the presently claimed therapeutic agent comprising (i) a miRNA oligonucleotide therapeutic conjugated to (ii) a "targeting element that binds to an ovarian cancer cell" as required by claim 1. Further, Lieberman does not teach or suggest "a cell of an ovarian cancer tumor microenvironment," as acknowledged by the Office Action, and as recited in claim 1. These deficiencies are not remedied by Dai, for at least the reasons set forth above. For example, Dai fails to disclose multiple elements recited in the present claims, including, e.g., miRNA-based therapeutic composition, targeting ligand, and linker/delivery, Thibonnier is silent with respect to ovarian cancer, and Zhao is silent with respect to miRNA oligonucleotide therapeutics, or the tumor microenvironment (as recited in claim 1). Further, Orellana is silent with respect to a targeting element that binds to a cell of an ovarian cancer tumor microenvironment, as presently claimed. For at least the reasons set forth above, Applicant submits the present claims are not obvious in view of Lieberman taken alone, or in combination with Dai, Thibonnier, Zhao, Orellana, or a combination thereof”.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Lieberman and Orellana teach all the limitations of the claims. Lieberman explicitly teaches both components recited in the claim: (i) miRNA, (ii) targeting elements that bind ovarian cancer, including CA 125 human ovarian cancer cell surface antigen. A person of ordinary skill in the art would have reasonably understood and been motivated to use the disclosed targeting moiety, such as antibodies against CA 125 human ovarian cancer cell surface antigen, in conjunction with miRNAs for ovarian cancer in order to enhance delivery specificity. Furthermore, Orellana teaches tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics. (e.g., abstract). Orellana teaches the 5’ end of a modified passenger strand of miR-34a (miR-34a-3p) was conjugated to folate-dibenzocyclooctyne (Fol-DBCO) using an unreleasable conformation (folate–miR-34a-3p: Fol-34a-3p) or a releasable conformation (folate–SS-miR-34a-3p: Fol-SS-34a-3p) which contains a reducible disulfide linkage (SS) between the miRNA and the folate molecule (e.g., paragraph 3rd, column 1, page 2; Fig 1A; Fig. S2A).
Accordingly, a person of ordinary skill in the art would have reasonably understood and been motivated to conjugate a therapeutically relevant miRNA directly to a targeting ligand (folic acid) whose receptor is overexpressed on cancerous cells such as folate receptors in ovarian cancer cells as a therapeutic anticancer drug for treatment of patients with ovarian cancer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637