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 .
DETAILED ACTION
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/10/2026 has been entered.
Status of Application/Amendment/Claims
Applicant's response filed 03/10/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 12/10/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 03/10/2026 claims 1, 2, 9, 10, 16, 23 and 24 are pending and currently under examination in the application.
New Claim Rejections
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 1, 2, 9, 10, 16, 23 and 24 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a nanoparticle comprising a TMV or TMV like particle (VLP) wherein a GM-CSF is encoded in a mRNA, having a 5’-cap, IRES and polyA tail, encapsulated within the TMV or TMV VLP and one or more Tat peptides fused to the TMV or TMV VLP and further wherein the nanoparticle is capable of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma in the a subject when the composition is introduced to or within a cell or tissue of the subject with melanoma.
The specification does not describe a nanoparticle as instantly claimed by structure or function. The specification describes the following:
[00227] Then mRNA encoding granulocyte- macrophage colony-stimulating factor (GM-CSF) will be delivered to demonstrate therapeutic protein delivery. The recent approval of T-VEC, an oncolytic virus therapy encoding GM-CSF for the treatment of melanoma patients highlights the clinical utility of cytokine delivery for cancer immunotherapy. We have already demonstrated the use of plant viruses for cancer immunotherapy; the combination with GM-CSF holds potential to potentiate the therapy.
[00228] To encapsulate EGFP and GM-CSF encoding mRNAs, the following gene will be designed: The EGFP or GM-CSF open reading frame (ORF) can be obtained from the National Center for Biotechnology Information (NCBI) (gene bank entry AFA52654.1 and AAA52578.1, respectively).
[00230] Based on length of the synthetic transcripts encoding EGFP and GM-CSF (see Fig. 7), TMV rods encapsulating a single copy of the gene are expected to measure only 20-30 nm in length (the length of the RNA defines the length of the nucleoprotein complex). To yield efficient assembly and to obtain higher aspect ratio particles, additional non-coding sequences.
[00233] A panel of cell lines will be used to determine transduction efficiency, first EGFP, then GM-CSF will be delivered. For EGFP expression levels will be quantified based on its fluorescence using flow cytometry and fluorescence imaging; GM-CSF expression will be quantified using specific antibodies and flow cytometry as well as quantitative western blots and ELISA methods.
Nothing in the instant specification describes the now claimed nanoparticle or a nanoparticle that possess the functions of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma in the a subject when the composition is introduced to or within a cell or tissue of the subject with melanoma. The specification does not describe a TMV or TMV VLP wherein an exogenous RNA encodes a GM-CSF that is non-covalently loaded in the particles and does not describe these particles with a Tat protein conjugated to the surface.
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As shown in the specification above, the specification shows how to obtain the nanoparticle and how it would function.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every variation of the expression construct. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the nanoparticle and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Enablement
Claims 1, 2, 9, 10, 16, 23 and 24 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The claims are drawn to a nanoparticle comprising a TMV or TMV like particle (VLP) wherein a GM-CSF is encoded by a RNA encapsulated with the TMV or TMV VLP and one or more Tat peptides fused to the TMV or TMV VLP and further wherein the nanoparticle is capable of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma in the a subject when the composition is introduced to or within a cell or tissue of the subject with melanoma.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
A thorough review of the patent and non-patent literature indicates that the state of the art demonstrating treatment of melanoma using a TMV or TMV VLP comprising a mRNA encoding GM-CSF was nascent at the time of filing.
Czapar et al. ("Tobacco mosaic virus delivery of phenanthriplatin for cancer therapy." ACS nano 10.4 (2016): 4119-4126) demonstrates TMV VLP can efficiently delivery anticancer agents wherein the agent was encapsulated in the TMV VLP and systemically delivered to a subject (see abstract, Figure 1 and page 4122). Czapar et al. does not describe using mRNA encoding a cytokine as an agent that is encapsulated in a TMV VLP and delivered to a subject for treatment of melanoma.
Murray et al. ("In situ vaccination with cowpea vs tobacco mosaic virus against melanoma." Molecular pharmaceutics 15.9 (2018): 3700-3716) teach in situ vaccination with Cowpea or TMV virus particles against melanoma and found that while in situ vaccination with TMV resulted in delayed tumor grown, lower potency and no efficacy was observed as compared to CPMV (see abstract and results page 3706). Murray et al. do not teach using TMV VLP to deliver a mRNA encoding GM-CSF for treatment of melanoma.
A review of the prior art does not provide a correlation between administration of a TMV or TMV VLP wherein a mRNA encoding GM-CSF is encapsulated within and treatment of melanoma.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that making and using the claimed nanoparticle would provide treatment of melanoma, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The specification describes in the following paragraphs: [00228] To encapsulate EGFP and GM-CSF encoding mRNAs, the following gene will be designed: The EGFP or GM-CSF open reading frame (ORF) can be obtained from the National Center for Biotechnology Information (NCBI) (gene bank entry AFA52654.1 and AAA52578.1, respectively). [00230] Based on length of the synthetic transcripts encoding EGFP and GM-CSF (see Fig. 7), TMV rods encapsulating a single copy of the gene are expected to measure only 20-30 nm in length (the length of the RNA defines the length of the nucleoprotein complex). To yield efficient assembly and to obtain higher aspect ratio particles, additional non-coding sequences.[00233] A panel of cell lines will be used to determine transduction efficiency, first EGFP, then GM-CSF will be delivered. For EGFP expression levels will be quantified based on its fluorescence using flow cytometry and fluorescence imaging; GM-CSF expression will be quantified using specific antibodies and flow cytometry as well as quantitative western blots and ELISA methods.
The working embodiment in the instant application are all prophetic and do not describe the claim nanoparticle or methods of treatment of melanoma using the nanoparticle.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification suggests trying to make the nanoparticle comprising a mRNA encoding GM-CSF and then potentially using it to treat melanoma in a cell or subject.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role GM-CSF plays in treatments of melanoma and undeveloped for a TMV or TMV VLP comprising a mRNA encoding a GM-CSF with the function of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma in the a subject when the composition is introduced to or within a cell or tissue of the subject with melanoma.. The specification does not provide sufficient guidance on using the claimed invention and without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636