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
Status of Application/Amendment/Claims
Applicant's response filed 07/02/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 04/07/2026 are hereby withdrawn.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 07/02/2026 claims 1, 2, 9, 10, 16, 23 and 24 are pending and currently under examination in the application.
The 112(a) and (b) rejections over claims 1, 9 and 23 have been withdrawn after further consideration and are allowable.
The rejections of claims 2, 10, 16 and 24 are maintained for the reasons of record.
Applicant has submitted a reference by Karan et al. and this reference cannot be considered without a proper IDS citing the reference.
Maintained 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.
Enablement
The rejection of claims 2, 10, 16 and 24 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 is maintained for the reasons of record.
Applicant’s arguments have been considered but are not persuasive. Applicant argues The Office Action fails to establish a prima facie case of non-enablement under 35 U.S.C. §112, as it does not demonstrate that undue experimentation would be required for a person of ordinary skill in the art to make and use the claimed invention. Instead, the rejection focuses primarily on whether treating melanoma with GM-CSF-loaded TMV particles was previously known.
In response, neither the prior art nor the instant specification provide a correlation between administration of a TMV or TMV VLP wherein a mRNA encoding GM-CSF is encapsulated within and treatment of melanoma such there would be undue experimentation to use the nanoparticle in the claimed method. The prior art teach T-VEC (a genetically modified oncolytic herpes virus that expresses GM-CSF) has shown efficacy against melanoma when administered as an in situ vaccine (of record in Applicant’s own work of Murray et al. page 3701 first para.). There is no correlation in the prior art or the instant specification that a genetically modified oncolytic herpes virus is similar to a TMV or TMV VLP and would provide evidence to enable the claimed method, particularly in methods of introducing the nanoparticle to a subject by intravenous administration or within any cell or tissue of the subject as claimed. Moreover, Murray et al. teach TMV or TMV VLP had a weak immune response against melanoma as compared to CPMV. Murray et al. do not teach using the TMV or TMV VLP as a carrier of mRNA expressing GM-CSF and therefor there would be undue experimentation to use the claimed nanoparticle, particularly in methods of introducing the nanoparticle to a subject by systemic administration or within any cell or tissue of the subject as claimed in treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma. Further, Murry et al. teach systemic administration of immune modulators lack tumor specificity and lead to serious immune side effects and suboptimal responses (see page 3701 past para.).
Applicant next argues enablement does not require proof that a claimed therapeutic composition has been clinically demonstrated to achieve a particular therapeutic result. The appropriate question is instead whether the specification teaches a skilled artisan how to make and use the claimed invention without undue experimentation. Again, the specification expressly identifies GM-CSF as a therapeutic cytokine and specifically discusses the clinical utility of GM-CSF delivery in melanoma therapy. For example, paragraph [227] (quoted by the Examiner) expressly states: "The recent approval of T-VEC ... encoding GM-CSF for the treatment of melanoma patients..." The specification further teaches delivery of GM-CSF-encoding mRNA using TMV particles and provides protocols for evaluating expression of the delivered cytokine.
The enablement rejection does not state the claimed nanoparticle has not been clinically demonstrated to achieve a particular therapeutic result. The claims specifically recite methods of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma and that is what the enablement rejection was based on. Nothing in the rejection mentions “clinically demonstrated to achieve a particular therapeutic result”. Furthermore, there is no correlation in the prior art or the instant specification that a genetically modified oncolytic herpes virus is similar to a TMV or TMV VLP and would provide evidence to enable the claimed method, particularly in methods of introducing the nanoparticle to a subject or within any cell or tissue of the subject as claimed.
Applicant further argues the rejection does not adequately address the factors identified in In re Wands. The level of skill in the art was high. The underlying technologies of mRNA synthesis, TMV particle assembly, noncovalent mRNA encapsulation, peptide conjugation chemistry, and evaluation of transgene expression were well known. The specification provides detailed guidance concerning implementation of these technologies. Above all, the Office Action does not identify any specific experimentation that would be required, much less experimentation that would be undue, to make and use the claimed compositions.
In response, the rejection specifically address this Wands factor by stating: “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 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”. And as stated in the O.A., the methods in the specification are prophetic and are not considered to provide sufficient enablement to practice the claimed invention.
Applicant argues The Office Action further appears to conflate the enablement requirement with a requirement that Applicants prove therapeutic efficacy. Again, the proper inquiry under 35 U.S.C. § 112(a), however, is whether the specification teaches a person of ordinary skill in the art to make and use the claimed invention without undue experimentation, not whether the application contains clinical data establishing the ultimate therapeutic success of the invention and cites In re Brana the Federal Circuit reversed an enablement rejection where the PTO had effectively required proof that the claimed anti-tumor compounds would work in humans, explaining that patentability does not depend upon demonstration of clinical efficacy. 51 F.3d 1560, 1566-67 (Fed. Cir. 1995).
In response, nowhere in the rejection is the Office requiring clinical data establishing the ultimate therapeutic success. Neither the specification nor the prior art provides guidance that one of skill can use the claimed nanoparticle in methods of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma. Applicant next argues Here, the Office Action repeatedly emphasizes the absence of demonstrated melanoma treatment and the prophetic nature of the disclosed studies. However, the specification provides detailed guidance for preparing TMV-based nanoparticles encapsulating GM-CSF mRNA, conjugating TAT peptides to the particle surface, administering the resulting compositions, and evaluating GM-CSF expression following delivery. Whether the disclosed compositions ultimately achieve a particular degree of therapeutic efficacy against melanoma is distinct from whether a skilled artisan could make and use the claimed invention. Therefore, because the rejection focuses on therapeutic efficacy instead of a skilled artisan's ability to make and use the claimed compositions, it applies an improper legal standard for enablement.
In response, 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 using it to treat melanoma in a cell, tissue or subject.
Lastly Applicant argues The Office Action asserts that the underlying art is "nascent" and that encapsulating exogenous therapeutic mRNA within TMV particles requires undue experimentation. In response Applicant submits herewith the article "A replicon-based COVID-19 vaccine candidate delivered by tobacco mosaic virus-like particles," published in Vaccine (53 (2025) 127063). The senior author of this publication is a co- inventor of the present application. While this reference post-dates the effective filing date of the present application, it is well-settled law that post-filing evidence is entirely admissible to substantiate the enabling nature of a specifications disclosure.
There is no dispute that post-filing art can be used to substantiate the enabling nature of a specifications disclosure however, the post-filing reference should be capable of demonstrating what was expected of the claimed prophetic methods. The post-filing reference of Karan et al. (filed with response to Arguments 07/02/2026) describe using a TMV for delivery of a mRNA vaccine, subcutaneously, for treatment of a viral infection such as COVID 19. This does not provide evidence of enablement for methods of treating, ameliorating, attenuating, and/or eliminating symptoms of melanoma by administering a nanoparticle, as claimed, introduced to a subject, such as systemically or within any cell or tissue of a subject.
The prior art is undeveloped for the role a nanoparticle comprising a TMV or TMV VLP comprising a mRNA encoding a GM-CSF plays in treatments of melanoma such that when administered to a subject or within a cell or tissue of a subject, it is capable of treating, ameliorating, attenuating or eliminating symptoms of melanoma in a subject, as instantly claimed.
The specification, prior art and post-filing art do 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.
Reasons for Indication of Allowable Subject Matter
Claims 1, 9 and 23 and are allowed. The prior art does not teach or make obvious a nanoparticle comprising a TMV or TMV VLP comprising a mRNA encoding a GM-CSF and a TAT protein conjugated to the surface of the TMV. The prior art of Czapar et al. (of record cited on 892 mailed 04/07/2026) teach TMV can be used to deliver an anticancer chemical compound in vivo (see page 4122). One of skill in the art would not have been motivated to make a nanoparticle comprising TMV and a mRNA encoding GM-CSF based on the prior art of Czapar et al. who teach using a chemical compound for use against breast cancer which is different than an expressed GM-CSF.
The prior art of Murray et al. (of record cited on 892 mailed 04/07/2026) describes previous work of using T-VEC (a genetically modified oncolytic herpes virus expressing GM-CSF) demonstrates efficacy against melanoma when administered as an in situ vaccine (page 3701 first para.). Murray references Johnson et al. ("Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma." Immunotherapy 7.6 (2015): 611-619) for this teaching and Johnson et al. teach that while GM-CSF, injected into melanoma lesions, demonstrated some response locally against melanoma in selected cases, their cutaneous toxicity and lack of a systemic therapeutic benefit have limited their clinical utility (page 612). Therefore it would not have been obvious to make the nanoparticle comprising TMV and mRNA encoding GM-CSF as claimed from the prior art of Johnson et al.
Murray et al. further describes the concerns of using a human pathogen as a therapeutic and suggests using plant viral particles for in situ vaccines. Murray et al. teach TMV can be administered to the tumor as an in situ vaccine that was capable of stimulating a weak immune response against melanoma (see page 3075). Although Murray et al. demonstrates using TMV as a vaccine, Murray et al. teach cowpea mosaic virus (CPMV) had a stronger immune response against melanoma compared to TMV.
It would not have been obvious to one of ordinary skill in the art to use TMV to make a nanoparticle comprising a mRNA encoding GM-CSF because while the prior art does provide motivation to use a plant virus as a vaccine, Murray et al. teach CPMV had a stronger immune response against melanoma. One of skill in the art would not have been make a TMV as compared to CPMV nanoparticle.
Conclusion
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 extension fee 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 KIMBERLY CHONG at (571)272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For more information about the PAIR system, see http://pair-direct.uspto.gov.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
Prosecution Insights