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 .
Support for the amendments is within the instant application specification.
Applicant’s amendment to the claims filed on 2/25/2026 in response to the Non-Final Rejection mailed on 10/23/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1, 4, 10, 14, 16-21, 32, 34 are pending and examined on the merits.
Claims 2-3, 5-9, 11-13, 15, 22-31, 33 are cancelled.
Withdrawn Rejections
The rejection of claims 1, 4, 10, 14, 16-21, 32, 34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), is withdrawn in view of Applicant’s amendment of claims 1, 18, 20 to recite ‘compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed’ and Applicant’s amendment of claim 19 to recite ‘further comprising.’
Maintained Claim Rejections - 35 USC § 112
Written Description
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.
The rejection of claims 1, 4, 10, 14, 16-17, 32, 34 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 is maintained. 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.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
Claims 1, 4, 10, 14, 16-17, 32, 34 are drawn to a nucleic acid molecule comprising a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9), wherein expression of the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO: 1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10. The structure of a functional variant encoding an inducible myc transcription factor operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 1 or 10 that is capable of accepting up to 25% sequence variation is a large number of sequences.
Claim 4 is drawn to the nucleic acid molecule of claim 1, wherein the mRNA molecule encodes at least one of a myc transcription factor as defined in SEQ ID NO: 11, 23 or 25 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 11, a cyclin T1 protein as defined in SEQ ID NO: 5 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 5, and a CDK9 protein as defined in SEQ ID NO: 7 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 7. The structure of a functional variant encoding an inducible myc transcription factor operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 11, 5 or 7 that is capable of accepting up to 25% sequence variation is a large number of sequences.
Claim 10 is drawn to the nucleic acid molecule of (Previously Presented): The nucleic acid molecule of wherein the nucleic acid construct or vector further comprises a nucleic acid sequence encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (CDK9) operably linked to the first regulatory sequence or a second regulatory sequence, wherein the nucleic acid sequence encodes a cyclin T1 protein as defined in SEQ ID NO: 5 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 5 and/or a CDK9 protein as defined in SEQ ID NO: 7 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 7. The structure of a functional variant encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (CDK9) operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 5 or 7 that is capable of accepting up to 25% sequence variation is a large number of sequences.
In this case, the specification discloses the following representative variants of myc transcription factor, cyclin T1 and cyclin- dependent kinase 9 (CDK9) as encompassed by the claims (i.e. myc transcription factor comprising SEQ ID NO: 11; cyclin T1 comprising SEQ ID NO: 5; cyclin- dependent kinase 9 (CDK9) comprising SEQ ID NO: 7; inducible myc transcription factor comprising SEQ ID NO: 1 or 10). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the extremely large number of variants of myc transcription factor (SEQ ID NO: 11), cyclin T1 (SEQ ID NO: 5), cyclin- dependent kinase 9 (CDK9) (SEQ ID NO: 7), inducible myc transcription factor (SEQ ID NO: 1 or 10) capable of accepting up to 25% sequence variation. The breadth of the claims encompasses a large number of sequences with 75% sequence identity to a variant of SEQ ID NOs: 1, 5, 7, 11 with 25% sequence variation whose structure is not fully defined.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to particularly point out the modifications to the claimed nucleic acids encoding transcription factors that encompass the functional variants thereof.
Accordingly, one of skill in the art would not accept the disclosure of functional variants having at least 75% sequence identity to myc transcription factor comprising SEQ ID NO: 11; cyclin T1 comprising SEQ ID NO: 5; cyclin- dependent kinase 9 (CDK9) comprising SEQ ID NO: 7; inducible myc transcription factor comprising SEQ ID NO: 1 or 10 as being representative of all functional variants thereof that increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of myc transcription factor; cyclin T1; cyclin- dependent kinase 9 (CDK9); inducible myc transcription factor, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
RESPONSE TO REMARKS: Beginning on p. 7 of Applicant’s remarks, in summary, Applicant contends that the specification teaches that myc is selected from c-myc, I-myc, or n-myc, pg. 24, lines 18-19, including an inducible form of myc, pg. 24, line 21, and provides the amino acid sequence of c-myc (SEQ ID NO: 11 ), I-myc (SEQ ID NO: 23), and n-myc (SEQ ID NO: 25), pg. 24, lines 24-25, and inducible forms of myc, (SEQ ID NO: 1; SEQ ID NO: 10), which include myc fused to a modified hormone-binding domain of estrogen receptor as described in the prior art, pg. 26, lines 27-34. Similarly, the specification provides the amino acid sequences of cyclin T1, SEQ ID NO: 5, and CDK9, SEQ ID NO: 7. As the specification includes the amino acid sequences of multiple myc proteins, cyclin T1, and CDK9, those skilled in the art would recognize that Applicants were in possession of the full genus of nucleic acids encoding these sequences, see MPEP 2163(II)(A)(3)(a)(iii). Applicant contends that those skilled in the art would recognize that functional variants of myc would have the same biological activity as wild-type myc, namely to promote transcriptional elongation by binding to cyclin T1.
This argument is found to be not persuasive. Examiner contends that the recited species of myc and cyclin T1 are not sufficient to satisfy the written description requirement. Especially since inducible forms of myc comprises a number of difference species of myc and modified species of myc with the recitation ‘myc fused to a modified hormone-binding domain of estrogen receptor.’ Additionally, the ‘modified hormone-binding domain of estrogen receptor’ upon which myc is fused is a large number of species. Examiner contends that Applicant’s own disclosure of ‘the nucleic acid molecules of the present invention may be mRNAs also encoding functional variants of a myc transcription factor, a cyclin T1 protein, and a CDK9 protein’ (Applicant Remarks Dated 2/25/2026: page 8, para 4; instant application claim 1) provides further support that Applicant does not disclose all possible species of the claimed myc and cyclin T1. It is suggested that Applicant amend the claims to a sequence identity of 90% of more to overcome the written description and scope of enablement 112a rejection. Applicant is reminded that the claims are read in light of the specification. Ultimately, Applicant needs to add further defining claim language that would lead one of ordinary skill in the art to the conclusion that Applicant fully disclosed the other 25% of the 75% sequence identity to myc.
Maintained Scope of Enablement Rejection
The scope of enablement rejection of claims 1, 4, 10, 14, 16-17, 32, 34 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is maintained. The specification, while being enabling for myc transcription factor comprising SEQ ID NO: 11; cyclin T1 comprising SEQ ID NO: 5; cyclin- dependent kinase 9 (CDK9) comprising SEQ ID NO: 7; inducible myc transcription factor comprising SEQ ID NO: 1 or 10 it does not reasonably provide enablement for all functional variants as encompassed by the claims with at least 75% sequence identity as a functional variant thereof capable of accepting up to 25% sequence variation. The specification does not enable any person skilled in the art to which it pertains, or with which it is mostly nearly connected, to make and/or use the invention commensurate in scope with these claims.“
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims:
Claims 1, 4, 10, 14, 16-17, 32, 34 are drawn to a nucleic acid molecule comprising a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9), wherein expression of the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO: 1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10. The structure of a functional variant encoding an inducible myc transcription factor operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 1 or 10 that is capable of accepting up to 25% sequence variation is a large number of sequences.
Claim 4 is drawn to the nucleic acid molecule of claim 1, wherein the mRNA molecule encodes at least one of a myc transcription factor as defined in SEQ ID NO: 11, 23 or 25 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 11, a cyclin T1 protein as defined in SEQ ID NO: 5 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 5, and a CDK9 protein as defined in SEQ ID NO: 7 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 7. The structure of a functional variant encoding an inducible myc transcription factor operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 11, 5 or 7 that is capable of accepting up to 25% sequence variation is a large number of sequences.
Claim 10 is drawn to the nucleic acid molecule of claim 1,wherein the nucleic acid construct or vector further comprises a nucleic acid sequence encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (CDK9) operably linked to the first regulatory sequence or a second regulatory sequence, wherein the nucleic acid sequence encodes a cyclin T1 protein as defined in SEQ ID NO: 5 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 5 and/or a CDK9 protein as defined in SEQ ID NO: 7 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 7. The structure of a functional variant encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (CDK9) operably linked to a first regulatory sequence having at least 75% sequence identity to SEQ ID NO 5 or 7 that is capable of accepting up to 25% sequence variation is a large number of sequences.
B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed variants of myc transcription factor, cyclin T1 and cyclin- dependent kinase 9 (CDK9), inducible myc transcription factor having at least 75% sequence identity are a large number of sequences. The structure of the claimed variants that increases at least one of proliferation, mitosis, and/or cytokinesis in a cell are a large number of variants.
It is well-known in the prior art that nucleic acids are paving the way for advanced therapeutics Pereira et al. (2022, Protocol, https://link.springer.com/protocol/10.1007/978-1-0716-2716-7_2) {herein Pereora}. Unveiling the genome enabled a better understanding of unique genotype–phenotype profiling. Investigating the different subtypes of DNA and RNA via sequencing and profiling is empowering the scientific community with valuable information, to be used in advanced therapeutics, tracking epigenetics linked to disease (abstract). Recent results from the application of nucleic acids in novel therapeutics and precision medicine are very encouraging, demonstrating great potential to treat cancer along with metabolic and genetic disorders (abstract).
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of myc transcription factor, cyclin T1 and cyclin- dependent kinase 9 (CDK9) as encompassed by the claims (i.e. myc transcription factor comprising SEQ ID NO: 11; cyclin T1 comprising SEQ ID NO: 5; cyclin- dependent kinase 9 (CDK9) comprising SEQ ID NO: 7; inducible myc transcription factor comprising SEQ ID NO: 1 or 10) that increases at least one of proliferation, mitosis, and/or cytokinesis in a cell. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the infinite functional variants with 75% sequence identity to myc transcription factor (SEQ ID NO: 11), cyclin T1 (SEQ ID NO: 5), cyclin- dependent kinase 9 (CDK9) (SEQ ID NO: 7), inducible myc transcription factor (SEQ ID NO: 1 or 10) that are capable of accepting up to 25% sequence variation. The breadth of the claims encompasses a large number of sequences with 75% sequence identity to variants of SEQ ID NOs: 1, 5, 7, 11 with 25% sequence variation.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
RESPONSE TO REMARKS: Applicant’s remarks filed on 2/25/2026 have been fully considered.
This argument is found to be not persuasive. The structure of the functional variants with 75% sequence identity to myc transcription factor (SEQ ID NO: 11), cyclin T1 (SEQ ID NO: 5), cyclin- dependent kinase 9 (CDK9) (SEQ ID NO: 7), inducible myc transcription factor (SEQ ID NO: 1 or 10) that are capable of accepting up to 25% sequence variation encode a large number of difference structures. It was not routine in the art at the time of the invention to make and test all of the infinite possible variants that encompass 25% sequence variation that increases at least one of proliferation, mitosis, and/or cytokinesis in a cell.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claims 1, 4, 10, 14, 17-19, 34 under 35 U.S.C. 102(a)(1) as being anticipated by Bancel et al. (WO 2013/151672 A2, International Publication Date: 10 October 2013, cited on PTO-892 dated 10/23/2025) {herein Bancel} as evidenced by Miller et al (2012, Clin Cancer Res, cited on PTO-892 dated 10/23/2025) {herein Miller} is maintained. See MPEP 2131.01 regarding multiple reference 102 rejections.
Claims 1, 4, 10, 14, 17, 34 are drawn to a nucleic acid molecule comprising a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9), wherein expression of the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO: 1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10.
Claims 18-19 are drawn to a composition comprising a first modified mRNA molecule and at least a second modified mRNA molecule, wherein the first modified mRNA molecule encodes a myc transcription factor and the second modified mRNA molecule encodes a cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) protein, wherein the modification is selected from at least one of a cap modification, a tail modification, a nucleoside modification and a untranslated region (UTR) modification, and wherein the composition increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed.
With respect to claims 1, 10, Bancel teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152). In addition, Bancel teaches the regulatory features of a untranslated region (UTR), such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017). The nucleic acid molecule encoding cycling dependent kinase 9 also encodes C-myc as Bancel teaches the nucleic acid molecule of the invention may encode one or more oncology related mRNA in the primary construct (para 00097 and 00098). it is well-known by those of ordinary skill in the art that C-Myc is a myc-transcription factor. As such, the C-Myc taught by Bancel is the same as the instant application myc as both genes are transcription factors. Regarding the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) and its usefulness in stimulating cellular proliferation. Evidentiary reference of Miller is cited to demonstrate that C-Myc is a master regulator of proliferation (abstract). As such, absent evidence otherwise, the nucleic acid construct comprising C-Myc and CDK9, taught by Bancel, will necessarily increase cellular proliferation. Bancel further teaches said construct may have a modification on at least one nucleoside (para 00017). Said construct is used for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032). To make the record clear, Examiner is interpreting the recitation ‘wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO:1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10’ of claim 1 to encompass 2 separate limitations due to the recitation ‘or.’ As such, Bancel anticipates the following limitation ‘wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification’ of claim 1 based on the 102a1 rejection.
With respect to claim 4, Bancel teaches the mRNA encodes CDK-9, SEQ ID NO: 5798 (instant application SEQ ID NO: 7) which is 100% identical to SEQ ID NO: 7 of the instant application (appendix A; Bancel: claim 17).
With respect to claim 14, Bancel teaches the selection of codon CAG for the regulation of host organisms (para 000142). Since CAG is being taught by Bancel to regulate host organisms, the CAG codon taught by Bancel is a regulatory sequence.
With respect to claim 17, Bancel teaches the administration may be by injection,
topical administration, ophthalmic administration and intranasal administration, of which are pharmaceutically acceptable carriers as they are commonly utilized for the administration of pharmaceutical materials (para 00019).
With respect to claims 18-19, Bancel teaches compositions of polynucleotides (mRNA) encoding one or more oncology-related polypeptides of interest (para 0029, 0028 and 0066). Bancel teaches the regulatory features of an untranslated region (UTR) can be incorporated into a nucleic acid molecule (para 000102). The UTR contain class I AU rich elements such as C-Myc (para 000106). It is known by those of ordinary skill in the art that C-Myc is a myc-transcription factor. As such, the C-Myc taught by Bancel is a first mRNA molecule that encodes a myc transcription factor. Regarding the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a nucleic acid sequence encoding a myc transcription factor, cyclin T1 or CDK9 and its usefulness in stimulating cellular proliferation. Evidentiary reference of Miller is cited to demonstrate that C-Myc is a master regulator of proliferation (abstract). As such, absent evidence otherwise, the nucleic acid molecules encoding C-Myc, taught by Bancel, would necessarily increase cellular proliferation. Bancel further teaches said constructs may have a modification on at least one nucleoside (para 00017). Furthermore, Bancel teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (page 152, para 0008) and a nucleic acid molecule encoding cyclin T1 as oncology-related primary constructs for the invention of interest (para 000182), wherein cyclin T1 is a second mRNA molecule and the nucleic acid molecule encoding cyclin dependent kinase 9 is a third mRNA molecule. Said nucleic acid (mRNA) molecule may encode one or more oncology related proteins (para 0029, 00097), of which is myC since Bancel teaches a regulatory feature, myC, may be added to the constructs (para 000106). In addition, said constructs may have a modification on at least one nucleoside (para 00017). As such, Bancel teaches a first modified mRNA molecule encoding myC; a second modified mRNA molecule encoding cyclin T1; a third mRNA molecule encoding cyclin dependent kinase 9 within a composition for the treatment of diseases. Said oncology-related mRNA encoding the oncology-related polypeptides of interest are selected for incorporation into vectors which will be amplified to produce cDNA templates (para 000139). Bancel further teaches the selection of codon CAG for the regulation of host organisms (para 000142). Since CAG is being taught by Bancel to regulate host organisms, the CAG codon taught by Bancel is a regulatory sequence operably linked to the construct as it is able to regulate expression. Bancel further teaches said constructs are used for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032).
With respect to claim 34, Bancel teaches the isolated polynucleotide formulation may include a nanoparticle (para 00020) of which the isolated polynucleotide formulation is the nucleic acid sequence comprising the construct of myC and CDK9.
For the reasons stated herein, the teachings of Bancel anticipate claims 1, 4, 10, 14, 17-19, 34.
RESPONSE TO REMARKS: Beginning on p. 16 of Applicant’s remarks, in summary, Applicant contends that Bancel et al. do not teach a nucleic acid molecule comprising a nucleic acid sequence encoding the combination of a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9). Bancel et al. teach that oncology-related polynucleotides may alter a biological and/or physiological process and lists over 24 of possible processes, Paragraph [0099],
but fail to teach which of these processes CDK9 is involved in. Applicant contends that Bancel et al. broadly define "oncology-related" as referring to any disease, disorder, condition, treatment, process, substance or compound related to any aspect of one or more hyperproliferative diseases, disorders and/or conditions including, but not limited to, cancer, Paragraph [01029]. As those skilled in the art would recognize, cancer is generally associated with aberrant proliferation, Bancel et al., Paragraph [0904], and cancer therapy would therefore seek to prevent this aberrant cell proliferation. As such, one skilled in the art would not find that the CDK9 that is used to reduce tumor growth in Bancel et al. could be used in a nucleic acid molecule that increases at least one of proliferation, mitosis, and/or cytokinesis in a cell as in claim 1.
This argument is found to be not persuasive. Examiner contends that Bancel teaches a nucleic acid molecule encoding cycling dependent kinase 9 that also encodes C-myc as Bancel teaches the nucleic acid molecule of the invention may encode one or more oncology related mRNA in the primary construct (para 00097 and 00098). Bancel further teaches increasing the level of an oncology-related polypeptide of interest comprising administering to said subject an isolated polynucleotide encoding said oncology-related polypeptide (Banel: instant application claim 1). It is the Examiner’s position that ‘increasing the level of said polynucleotide would necessarily entail an increase in proliferation, mitosis, and/or cytokinesis as it is well-known in the art that the process of increasing the levels of polynucleotide in a cell involves the growth cycle which is known by those of ordinary skill in the art to include the following phases: G1, S, G2, mitosis following by cytokinesis. As such, Examiner maintains that Bancel anticipates the limitations of the instant application. Examiner contends that Bancel is ‘reducing’ the symptoms of cancer, however to do so, Bancel is increasing the level of the polynucleotide (para 00011). It is noted that Applicant does not clearly define the type of cell that contains the claimed polynucleotide and would exhibit an increased proliferation, mitosis, and/or cytokinesis. Bancel teaches the cells upon which the polynucleotide are isolated include, but are not limited to CHO cells, HeLa cells, etc. (para 000786). As such, Examiner maintains that the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, claim language, does not require steps to be performed or limit the claim to a particular structure (cell) and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) and its usefulness in stimulating cellular proliferation within any cell. Evidentiary reference of Miller is cited to demonstrate that C-Myc is a master regulator of proliferation (abstract). As such, absent evidence otherwise, the nucleic acid construct comprising C-Myc and CDK9, taught by Bancel, will necessarily increase cellular proliferation within the claimed ‘a cell.’
Applicant contends that while Bancel et al. mentions c-myc in Paragraph [0106], those skilled in the art would recognize that Bancel et al. only provides that the Class I AREs within c-myc could be incorporated into the oncology-related polynucleotide to modulate stability of the polynucleotide but do not teach that c-myc itself is incorporated into the polynucleotide or that c-myc is an oncology-related polynucleotide, particularly since c-myc is not among the 4,511 possible "oncology-related proteins" in Table 6. Applicant contends that even if c-myc were disclosed as an oncology-related protein that could be selected for use according to Bancel et al., there is nothing in either reference that would lead one skilled in the art to select cyclin T1 from the 4,511 options in Table 6 and then further selecting c-myc and thereby arrive at the specific combination of a nucleic acid molecule comprising a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9).
This argument is found to be not persuasive. Examiner contends that Bancel explicitly teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152). In addition, Bancel teaches the regulatory features of a untranslated region (UTR), such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017). Examiner contends, that based on claim language, Applicant requires cyclin T1 OR CDK9. Examiner contends that Bancel teaches CDK9 (appendix A, para 000182, page 152). It is noted that Applicant has disclosed within the instant Applicant claims any use of the claimed construct in oncology-related materials.
Maintained Claim Rejections - 35 USC § 103
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 rejection of claims 16, 32 under 35 U.S.C. 103 as being unpatentable over Bancel et al. (WO 2013/151672 A2, International Publication Date: 10 October 2013, cited on PTO-892 dated 3/31/2025) {herein Bancel} as applied to claims 1, 4, 10, 14, 17-19, 34 in view of Cambier et al. (US 10,760,055 B2. Date Filed: Jul. 23, 2018, Date Published: Sep. 1, 2020, cited on PTO-892 dated 3/31/2025) {herein Cambier} as evidenced by Miller et al (2012, Clin Cancer Res, cited on PTO-892 dated 10/23/2026) {herein Miller} is maintained.
Claim 16 is drawn to the nucleic acid molecule of claim 1, wherein the vector is a viral vector.
Claim 32 is drawn to a host cell comprising the nucleic acid molecule of claim 1, wherein the host cell is a eukaryotic cell, wherein the eukaryotic cell is a mammalian cell selected from a heart, brain or kidney cell.
The teachings of Bancel as applied to claims 1, 4, 10, 14, 17-19, 34 are set forth in the 35 USC 102a1 rejection above.
However, Bancel does not teach the product of claim 16, wherein the vector is a viral vector (claim 16). The product of claim 32, wherein the host cell is a eukaryotic cell, wherein the eukaryotic cell is a mammalian cell selected from a heart, brain or kidney cell (claim 32).
With respect to claim 16, Cambier teaches retroviral vectors encoding myc (column 39, lines 29).
With respect to claim 32, Cambier teaches vectors with the protooncogene, of which is myc, can be transfected into a mammalian host cell (column 24, lines 12-15).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Bancel that teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152), wherein a regulatory feature such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017) thereby encoding a construct that contains cycling dependent kinase 9 and C-myc (para 00097 and 00098) with a modification on at least one nucleoside (para 00017) and wherein the C-Myc increases cellular proliferation for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032) or combine the teaching of Cambier because Cambier teaches retroviral vectors encoding myc (column 39, lines 29) and the utilization of mammalian host cells for expression (column 24, line 15).
One of ordinary skill in the art would be motivated to either use the teachings of Bancel et al. by itself or combine the teachings of Cambrier because Cambrier provides the motivation for Bancel to utilize a viral vector for the expression of modified mRNA encoding myc, cyclin T1 and CDK-9 as the viral vectors can be modified with specific surface expressed molecules that target stem-cell growth factor ligands (column 24, lines 27-29). In addition, Bancel would be motivated to utilize mammalian host cells for the expression of modified mRNA encoding myc, cyclin T1 and CDK-9 as said genes are mammalian genes that are optimally expressed in mammalian cells. One of ordinary skill in the art knowing the benefit of identifying appropriate vectors and host cells that allow for the appropriate expression of mRNA based on the teachings of Bancel and Cambrier would have a reasonable expectation of success to combine a viral vector and mammalian host cells for the expression of modified mRNA encoding myc and cyclin T1 and/or CDK-9 as said genes are mammalian, therefore would be appropriately expressed. Furthermore, since viral vectors can be modified to target specific growth factor ligands, one of ordinary skill in the art would have a reasonable expectation of success that cloning the modified mRNA of the instant application into the viral vector would result in a product that is generated to specifically target ligands of interest for the treatment of diseases.
One of skill in the art would have a reasonable expectation of success to make and use the composition comprising modified mRNA constructs containing myC, cyclin T1 and/or CDK-9 within expression vectors because Bancel provides the teaching of a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152), wherein a regulatory feature such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017) thereby encoding a construct that contains cyclin dependent kinase 9 and C-myc (para 00097 and 00098) with a modification on at least one nucleoside (para 00017) and wherein the C-Myc increases cellular proliferation for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032). Whereas, Cambrier teaches retroviral vectors encoding myc (column 39, lines 29) and the utilization of mammalian host cells for their expression (column 24, line 15). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Applicant's arguments dated 2/25/2026 have been fully considered but they are not persuasive. Beginning on p. 21 of Applicants’ remarks, Applicants in summary contends
that Gambier et al. (corrected to Cambier et al) do not correct the deficiencies of Bancel et al. and is cited for teaching a nucleic acid molecule comprising a protooncogene that can be MYC. Cambier et al. do not teach myc in combination with either cyclin T1 and/or CDK9 and there is no indication that they should be used with the oncology-related polypeptides from Bancel et al.
This argument is found to be not persuasive. Examiner contends that Cambrier provides the motivation for Bancel to utilize a viral vector for the expression of modified mRNA encoding myc, cyclin T1 and CDK-9 as the viral vectors can be modified with specific surface expressed molecules that target stem-cell growth factor ligands (column 24, lines 27-29). Additionally, Examiner contends that Bancel teaches myc in combination with CDK9 (para 000102 and 00017).
Applicant contends that Bancel et al. inhibits proliferation while Cambier et al. promotes it, and there is nothing that would suggest that the combination of a myc transcription factor and cyclin T1 /GDK9 would be able to increase at least one of proliferation, mitosis, and/or cytokinesis as in claim 20.
This argument is found to be not persuasive. Examiner contends Cambrier provides the motivation for Bancel to utilize a viral vector for the expression of modified mRNA encoding myc, cyclin T1 and CDK-9 as the viral vectors can be modified with specific surface expressed molecules that target stem-cell growth factor ligands (column 24, lines 27-29). Furthermore, it is known by those of ordinary skill in the art that viral vectors act as highly efficient delivery systems. They significantly increase gene expression levels because their natural evolutionary machinery is designed to invade cells, overcome cellular defenses, and hijack host translation mechanisms. This enables rapid, robust transcription and translation of targeted genetic sequences for therapeutic or experimental purposes.
Applicant contends that Applicants unexpectedly found that a composition comprising a first
vector and at least a second vector, wherein the first vector comprises a nucleic acid sequence encoding an inducible myc transcription factor operably linked to a regulatory sequence and the second vector comprises a nucleic acid sequence encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (GDK9) operably linked to a regulatory sequence unexpectedly was able to increase proliferation, mitosis, and/or cytokinesis in a cell, including non-proliferating cells. It is well settled that one may rebut a prima facie case of obviousness based on unexpected results by demonstrating that the claimed inventions exhibits some superior property or advantage that a person of ordinary skilled in the art would have found surprising or unexpected.
This argument is found to be not persuasive. Examiner contends that Applicant has not provided sufficient information to lead to ‘unexpected results’ as Applicant has not clearly defined all limitations of the claim. For example, Applicant has not clearly defined within the instant application claims the type of cell that contains said nucleotide. Especially since Bancel clearly anticipates the limitations of the independent instant application claims with the teaching of a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152). In addition, Bancel teaches the regulatory features of a untranslated region (UTR), such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017). As such, Applicant has not met the burden of ‘unexpected results.’
Maintained Claim Rejections - 35 USC § 103
The rejection of claims 20-21 under 35 U.S.C. 103 as being unpatentable over Bancel et al. (WO 2013/151672 A2, International Publication Date: 10 October 2013, cited on PTO-892 dated 3/31/2025) {herein Bancel}, Cambier et al. (US 10,760,055 B2. Date Filed: Jul. 23, 2018, Date Published: Sep. 1, 2020, cited on PTO-892 dated 3/31/2025) {herein Cambier} as evidenced by Miller et al (2012, Clin Cancer Res, cited on PTO-892 dated 10/23/2025) {herein Miller} is maintained.
Claims 20-21 are drawn to a composition comprising a first vector and at least a second vector, wherein the first vector comprises a nucleic acid sequence encoding an inducible myc transcription factor operably linked to a regulatory sequence and the second vector comprises a nucleic acid sequence encoding a cyclin T1 and/or a cyclin-dependent kinase 9 (CDK9) operably linked to a regulatory sequence, and wherein the composition increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed.
With respect to claims 20-21, Bancel teaches compositions of polynucleotides encoding one or more oncology-related polypeptides of interest (para 0028). Furthermore, Bancel teaches the regulatory features of a untranslated region (UTR), such as C-Myc (para 000106), can be incorporated into a nucleic acid molecule (para 000102). It is known by those of ordinary skill in the art that C-Myc is a myc-transcription factor. As such, the C-Myc taught by Bancel is a first mRNA molecule that encodes a myc transcription factor. Regarding the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a first vector encoding an inducible myc transcription factor and a second vector encoding a cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) operantly linked to a regulatory sequence and its usefulness in stimulating cellular proliferation, mitosis and/or cytokinesis in a cell. Evidentiary reference of Miller is cited to demonstrate that C-Myc is a master regulator of proliferation (abstract). As such, absent evidence otherwise, the nucleic acid construct comprising C-Myc, taught by Bancel, will necessarily increase cellular proliferation. Bancel further teaches said construct may have a modification on at least one nucleoside (para 00017). In addition, Bancel teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (page 152, para 0008) and a nucleic acid molecule encoding cyclin T1 as oncology-related primary constructs for the invention of interest (para 000182). Examiner is interpreting cyclin T1 as a second mRNA molecule. Examiner is interpreting the nucleic acid molecule encoding cyclin dependent kinase 9 as third mRNA molecule. Said nucleic acid molecule may encode one or more oncology related proteins (para 00097). As such, Examiner is interpreting Bancel to teach a first modified mRNA molecule encoding myC; a second modified mRNA molecule encoding cyclin T1; a third mRNA molecule encoding cyclin dependent kinase 9 within a composition for the treatment of diseases. Said oncology-related mRNA encoding the oncology-related polypeptides of interest are selected for incorporation into vectors which will be amplified to produce cDNA templates (para 000139). As such, Examiner is interpreting the first, second and third modified mRNA taught by Bancel to be within first, second and third vectors. Bancel further teaches the selection of codon CAG for the regulation of host organisms (para 000142). Since CAG is taught by Bancel to regulate host organisms, the CAG codon taught by Bancel is a regulatory sequence. Bancel further teaches said constructs are used for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032).
However, Bancel does not teach the composition of claims 20-21 of an inducible myc transcription factor operably linked to a regulatory sequence (claims 20-21).
With respect to claims 20-21, Cambier teaches a nucleic acid molecule comprising a protooncogene (column 3, lines 18-19). The protooncogene to be used in the invention includes MYC (column 22, lines 12-14). Said genes may be operatively linked to an expression control sequence (column 16, lines 16-17) and inducible (column 19, line 36). Said protooncogene promotes proliferation (column 19, line 35 and column 22, lines 12-13).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Bancel that teaches a first mRNA molecule that encodes a myc transcription factor; a nucleic acid molecule encoding cyclin dependent kinase 9 (page 152, para 0008); a nucleic acid molecule encoding cyclin T1 as oncology-related primary constructs for the invention of interest (para 000182) with modifications on at least one nucleoside (para 00017) incorporated into vectors (para 000139) or combine the teaching of Cambier because Cambier teaches the MYC protooncogene promotes the proliferation of cells (column 19, line 35 and column 22, lines 12-13) and are inducible (column 19, line 36) when operatively linked to an expression control sequence (column 16, lines 16-17).
One of ordinary skill in the art would be motivated to either use the teachings of Bancel et al. by itself or combine the teachings of Cambrier because Cambrier provides the motivation for Bancel to link the modified mRNA constructs to an inducible myc transcription factor so that the protooncogene can be activated and deactivated (i.e., turned on or turned off) as desired to either maintain the stem cell in an immortalized state or to allow it to differentiate into a desired cell type (column 21, lines 57-61). One of ordinary skill in the art knowing the benefit of controlling the expression of modified mRNA that encode MyC, CDK9 and/or cyclin T1 based on the teachings of Bancel and Cambrier would have a reasonable expectation of success to combine the inducible promoter to control the transcription of myc with the mRNA modified constructs as doing so will allow for tighter control and regulation of the modified mRNA construct and better regulated experimental conditions such as cellular proliferation.
One of skill in the art would have a reasonable expectation of success to make and use the composition comprising modified mRNA constructs containing myC, cyclin T1 and/or CDK-9 within expression vectors, wherein myC is under an inducible expression system and incorporated it into vectors because Bancel provides the teaching of a first mRNA molecule that encodes a myc transcription factor; a nucleic acid molecule encoding cyclin dependent kinase 9 (page 152, para 0008); a nucleic acid molecule encoding cyclin T1 as oncology-related primary constructs for the invention of interest (para 000182) with modifications on at least one nucleoside (para 00017) incorporated into vectors (para 000139). Whereas, Cambrier teaches a nucleic acid molecule comprising a protooncogene (column 3, lines 18-19), MYC (column 22, lines 12-14), operatively linked to an inducible expression control sequence (column 16, lines 16-17 and column 19, line 36), of which said protooncogene promotes cellular proliferation (column 19, line 35 and column 22, lines 12-13). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Applicant's arguments dated 2/25/2026 have been fully considered but they are not persuasive. In summary, Applicant contends that Miller et al. do not correct the deficiencies of Bancel et al. and is cited as evidence that c-myc is a master regulator of proliferation. However, Miller et al. only provide a review of the functions of c-myc including its role in transformation, proliferation, glycolysis, mitochondrial biogenesis and glutamine metabolism, abstract. Miller et al. further note that "efforts to utilize c-myc as a therapeutic target have been quite frustrating," abstract, and provide multiple teachings that c-myc can contribute to the cause of tumors and cancers, pg. 3,r 4. Therefore, one skilled in the art would not find c-myc could be used as an oncology related protein in Bancel et al.
This argument is found to be not persuasive. Examiner contends that Miller was utilized as an evidentiary reference to demonstrate that C-Myc is a master regulator of proliferation (abstract). Thereby the nucleic acid construct comprising C-Myc and CDK9, taught by Bancel, will necessarily increase cellular proliferation.
Maintained Claim Rejections - 35 USC § 103
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 rejection of claims 1, 4, 10, 14, 17, 34 under 35 U.S.C. 103 as being unpatentable over Bancel et al. (WO 2013/151672 A2, International Publication Date: 10 October 2013, cited on PTO-892 dated 3/31/2025) {herein Bancel} in view of Johnson et al (US 20080131404A1, Date Published: June 5, 2008, cited on PTO-892 dated 10/23/2026) {herein Johnson} as evidenced by Miller et al (2012, Clin Cancer Res, cited on PTO-892 dated 10/23/2026) {herein Miller} is maintained.
As amended, claims 1, 4, 10, 14, 17, 34 are drawn to a nucleic acid molecule comprising a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9), wherein expression of the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell compared to the level of at least one of proliferation, mitosis, and/or cytokinesis in a cell where the nucleic acid molecule is not expressed, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO: 1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10.
With respect to claims 1, 10, Bancel teaches a nucleic acid (mRNA) molecule encoding cyclin dependent kinase 9 (appendix A, para 0029, 000182, page 152). In addition, Bancel teaches the regulatory features of a untranslated region (UTR), such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017). As such, the nucleic acid molecule encoding cycling dependent kinase 9 to also encode C-myc as Bancel also teaches the nucleic acid molecule of the invention may encode one or more oncology related mRNA in the primary construct (para 00097 and 00098), of which is C-Myc and CDK-9. In addition, it is well-known by those of ordinary skill in the art that C-Myc is a myc-transcription factor. As such, the C-Myc taught by Bancel is the same as the instant application myc as both genes are transcription factors. Regarding the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a nucleic acid sequence encoding a myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) and its usefulness in stimulating cellular proliferation. Evidentiary reference of Miller is cited to demonstrate that C-Myc is a master regulator of proliferation (abstract). As such, absent evidence otherwise, the nucleic acid construct comprising C-Myc and CDK9, taught by Bancel, will necessarily increase cellular proliferation. Bancel further teaches said construct may have a modification on at least one nucleoside (para 00017). Said construct is used for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032). To make the record clear, Examiner is interpreting the recitation ‘wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, and wherein: (i) the nucleic acid molecule is a mRNA molecule and comprises at least one modification selected from a cap modification, a tail modification, a nucleoside modification and an untranslated region (UTR) modification; or (ii) the nucleic acid molecule is nucleic acid construct or vector, and wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO:1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10’ of claim 1 to encompass 2 separate limitations because of the recitation ‘or’ separating the 2 limitations, of which one is a requirement of the claim.
With respect to claim 4, Bancel teaches the mRNA encodes CDK-9, SEQ ID NO: 5798 (instant application SEQ ID NO: 7) (appendix A; Bancel: claim 17).
With respect to claim 14, Bancel teaches the selection of codon CAG for the regulation of host organisms (para 000142). Since CAG is being taught by Bancel to regulate host organisms, the CAG codon taught by Bancel is a regulatory sequence. Since CAG is being taught by Bancel to regulate host organisms, the CAG codon taught by Bancel is a regulatory sequence operably linked to the construct as it is able to regulate expression.
With respect to claim 17, Bancel teaches the administration may be by injection, topical administration, ophthalmic administration and intranasal administration (para 00019).
With respect to claim 34, Bancel teaches the isolated polynucleotide formulation may include a nanoparticle (para 00020), of which is the isolated polynucleotide formulation to be the nucleic acid sequence comprising CDK9.
However, Bancel does not teach the product of claim 1, wherein the nucleic acid sequence encodes an inducible myc transcription factor operably linked to a first regulatory sequence, wherein the nucleic acid sequence encodes an inducible myc transcription factor as defined in SEQ ID NO:1 or 10 or a functional variant thereof having at least 75% sequence identity to SEQ ID NO: 1 or 10.
With respect to claim 1, Johnson teaches SEQ ID NO: 2 (para 0026), which is SEQ ID NO: 1 of the instant application, (appendix B) is an inducible c-myc protein and an osteogeny reporter (abstract) that is responsible for conferring conditionally immortal character to mammalian cells (para 0010). Regarding the limitation “wherein the nucleic acid molecule increases at least one of proliferation, mitosis, and/or cytokinesis in a cell, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between a nucleic acid sequence encoding a c-myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) and its usefulness in stimulating cellular proliferation.
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Bancel that teaches a nucleic acid molecule encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152), wherein a regulatory feature such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017) thereby encoding a construct that contains cycling dependent kinase 9 and C-myc (para 00097 and 00098) with a modification on at least one nucleoside (para 00017) and wherein the C-Myc increases cellular proliferation for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032) or combine the teaching of Johnson because Johnson teaches SEQ ID NO: 1 (appendix B) is a c-myc protein and an osteogeny reporter (abstract) responsible for conferring conditionally immortal character to mammalian cells (para 0010).
One of ordinary skill in the art would be motivated to either use the teachings of Bancel et al.) by itself or combine the teachings of Johnson because Johnson provides the motivation for Bancel to operatively link an inducible c-myc transcription factor as defined by SEQ ID NO: 1 (appendix B) as doing so maintains the ability of the construct to be activated by the oestrogen receptor ligand and activate transcription leading to cell proliferation (para 0026). Additionally, said construct has a mutation that prevents high affinity binding to 17 -oestradiol, without affecting the high-affinity binding to the ligand 4-OHT (para 0026). to a regulatory sequence.
One of ordinary skill in the art knowing the benefit of a inducible conditionally immortal cell for the expression of product based on the teachings of Bancel and Johnson would have a reasonable expectation of success to combine an inducible c-myc transcription factor (instant application SEQ ID NO: 1) with a regulatory sequence as said construct would allow for the tightly regulated expression of c-myc transcription factor and at least one of cyclin T1 and/or cyclin-dependent kinase 9 (CDK9) from immortal cells. Furthermore, said construct would save time and resources generated towards cell-turnover during cell passages.
One of skill in the art would have a reasonable expectation of success to make and use the modified mRNA constructs comprising myC and cyclin T1 and/or CDK-9 within expression vectors with an inducible c-myc transcription factor (instant application SEQ ID NO: 1, appendix B) because Bancel provides the teaching of a nucleic acid molecule (mRNA) encoding cyclin dependent kinase 9 (appendix A, para 000182, page 152), wherein a regulatory feature such as C-Myc (para 000106), can be incorporated into the nucleic acid molecule (para 000102 and 00017) thereby encoding a construct that contains cyclin dependent kinase 9 and C-myc (para 00097 and 00098) with a modification on at least one nucleoside (para 00017) and wherein the C-Myc increases cellular proliferation for the manufacture and/or formulation of modified mRNA for the treatment of cancers (para 0009, 00010, 00032). Whereas, Johnson teaches SEQ ID NO: 1 (appendix B) is an inducible c-myc protein and an osteogeny reporter (abstract) that is responsible for conferring conditionally immortal character to mammalian cells (para 0010). Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Applicant's arguments dated 2/25/2026 have been fully considered but they are not persuasive. Beginning on p. 30 of Applicants’ remarks, Applicants in summary contends
that one skilled in the art would not be motivated to combine the teachings of immortalizing a cell line as in Johnson et al. for the treatment of cancer or hyperproliferative disorders as in Bancel et al. and there is no indication as to what technical effect would result from the combination of oncology-related polynucleotides for treating cancer/hyperproliferative disorders and a c-myc/oestrogen fusion peptide that conditionally increases proliferation.
This argument is found to be not persuasive. Examiner contends that Applicant does not claim the polynucleotide of the invention for the treatment of cancer or hyperproliferative disorders. Examiner contends that Applicant simply claims said polynucleotide for the increased proliferation, mitosis, and/or cytokinesis in a cell.
Applicant contends that Johnson et al. but does not mention cyclin T1 and/or CDK9 and there is no indication that c-myc could be used with the oncology-related polypeptides from Bancel et al.
Examiner contends that Johnson provides the motivation for Bancel to operatively link an inducible c-myc transcription factor as defined by SEQ ID NO: 1 (appendix B) as doing so maintains the ability of the construct to be activated by the oestrogen receptor ligand and activate transcription leading to cell proliferation (para 0026).
Conclusion
Status of the claims
Claims 1, 4, 10, 14, 16-21, 32, 34 are pending and examined on the merits.
Claims 2-3, 5-9, 11-13, 15, 22-31, 33 are cancelled.
Claims 1, 4, 10, 14, 16-21, 32, 34 are rejected.
No claims are in condition for allowance.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Alignment of SEQ ID NO: 7 (cdk-9) instant application vs Bancel 2013
Query Match 100.0%; Score 1951; Length 489;
Best Local Similarity 100.0%;
Matches 372; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMENEKEGFP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 118 MAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMENEKEGFP 177
Qy 61 ITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLLSNVLVK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 178 ITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLLSNVLVK 237
Qy 121 FTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAFSLAKNS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 238 FTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAFSLAKNS 297
Qy 181 QPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTEQHQLAL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 298 QPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTEQHQLAL 357
Qy 241 ISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDKLLVLDP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 358 ISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDKLLVLDP 417
Qy 301 AQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQSTNQSRNP 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 418 AQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQSTNQSRNP 477
Qy 361 ATTNQTEFERVF 372
||||||||||||
Db 478 ATTNQTEFERVF 489
Appendix B
Alignment of SEQ ID NO: 1 with Johnson et al SEQ ID NO: 2
Query Match 94.5%; Score 3674; Length 754;
Best Local Similarity 94.8%;
Matches 717; Conservative 11; Mismatches 22; Indels 6; Gaps 3;
Qy 1 MPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPTPP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPTPP 60
Qy 61 LSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDPD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDPD 120
Qy 121 DETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARGHSVCSTSSLYLQD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARGHSVCSTSSLYLQD 180
Qy 181 LSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAFSPSSDSLLSSTESSPQGSPEPLVL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAFSPSSDSLLSSTESSPQGSPEPLVL 240
Qy 241 HEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKRSESGSPSAGGHSKOOHSPLVLKRC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 HEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKRSESGSPSAGGHSKOOHSPLVLKRC 300
Qy 301 HVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSPRSSDTEENVKRRTHN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 HVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSPRSSDTEENVKRRTHN 360
Qy 361 VLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSVQAEEQKLISEEDLL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 VLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSVQAEEQKLISEEDLL 420
Qy 421 RKRREQLKHKLEQLRDP----GSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSAL 476
||||||||||||||||| |::||||||||||||| || :|||| |||||||||||||
Db 421 RKRREQLKHKLEQLRDPRNEMGASGDMRAANLWPSPL-IKHTKKNSPALSLTADQMVSAL 479
Qy 477 LDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLL 536
||||||::||||||:||||||||||||||||||||||||||||||||| || ||||||||
Db 480 LDAEPPMIYSEYDPSRPFSEASMMGLLTNLADRELVHMINWAKRVPGFGDLNLHDQVHLL 539
Qy 537 ECAWLEILMIGLVWRSMEHPVKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMN 596
|||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||
Db 540 ECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMN 599
Qy 597 LQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQ 656
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 LQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQ 659
Qy 657 QHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEAADAHRLHAPTSRGGAS 716
||:|||||||||||||||||| |||||:|||||||| |||||| |||||||| || |
Db 660 QHRRLAQLLLILSHIRHMSNKRMEHLYNMKCKNVVP-YDLLLEMLDAHRLHAPASRMGVP 718
Qy 717 VEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV 752
|| |: ||| |||:|||| ||| |||||| |:
Db 719 PEEPSQTQLATTSSTSAHSLQTYYIPPEAEGFPNTI 754
Prosecution Insights