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 .
Application Status
This action is written in response to applicant’s correspondence received on 6/9/2026. Claims 1, 4-11, 21, 23, 25-26, 29, 70, 85, and 87 are pending. Claims 1, 4, 6, 21, 23, 26, 29, 70, 85, and 87 have been amended. Claims 2-3, 12-20, 22, 24, 27-28, 30-69, 71-84, 86, and 88-131 have been cancelled. All pending claims are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. This Office Action is Final.
Claim Rejections - 35 USC § 103 – Maintained/Updated in Response to Amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-11, 21, 23, 25-26, 29, 70, 85, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Ashmead (US 2017/0173267 A1, published 6/22/2017) in view of Horhota (WO 2020/061457 A1, published 3/26/2020).
Regarding claim 1, Ashmead teaches a syringe silicone-free syringe barrel comprising at least one therapeutic (throughout, for instance see claim 1 of Ashmead). The combination of syringe and therapeutic can reasonably be interpreted to be a “kit,” as such a term broadly encompasses the presence of items together. Furthermore, Ashmead teaches that the therapeutic can be RNA interference (i.e., RNA, throughout, see claim 3 of Ashmead). Ashmead teaches that the syringes can be 1-3 ml volume syringes (paragraph 100).
Ashmead does not specifically teach that the RNA is formulated in a lipid carrier. Ashmead, while teaching the delivery of therapeutic RNA such as RNAi and antisense RNA (e.g., claim 3) does not teach that the RNA is mRNA. Ashmead does not teach that the mRNA is at a concentration less than 200 ug/ml.
Horhota is a patent document which teaches methods of effective administration and preparation of lipid nanoparticles (Title, Abstract, and throughout). Horhota teaches that lipid-based carriers are known to be “effective as transport vehicles into cells and/or intracellular compartments for biologically active substances such as small molecule drugs, proteins, and nucleic acids,” (paragraph 4). Thus, Horhota teaches a motivation to incorporate the use of lipid nanoparticles when delivering a nucleic acid such as RNA, as such carriers are known to improve efficacy of delivering RNA (Background, paragraphs 3-4). Furthermore, Horhota also teaches that such formulations that they teach can be administered using a syringe (e.g., paragraph 186). Horhota teaches that the RNA can be mRNA (e.g., paragraph 433 and throughout). Horhota teaches that mRNA vaccines are administered at a dose between 25-100 ug (e.g., paragraphs 610-611). Horhota reduced to practice mRNAs formulated in lipid nanoparticles at concentrations below 100 ug/ml (see Tables 3 and 20). Thus, Horhota not only teaches the usefulness of using lipid-based carriers to deliver RNAs such as mRNAs but also teaches that mRNA vaccines are administered at a known dose of 25-100 ug and has also reduced to practice formulations of mRNA/lipid carriers where the mRNA is at a concentration around and below 100 ug/ml (paragraphs 4, 540, 610-611, Tables 3 and 20).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the syringes and therapeutic compositions taught by Ashmead to include lipid-carrier based mRNAs at a concentration of less than 200 ug/ml, as taught by Horhota, because such a combination is the simple combination of known prior art elements with predictable success. In the present case, such syringes are already known, where furthermore the use of lipid particles to deliver mRNA at a concentration below 200 ug/ml is similarly known, where such concentrations of mRNAs have been reduced to practice as taught by Horhota. Furthermore, the combination is not simply the combinations of known prior art elements. To the contrary, the practitioner would be motivated to combine the teachings of Horhota with those of Ashmead because Horhota teaches advantages to using lipid particles for the delivery of RNA such as mRNA, where furthermore the practitioner would be specifically motivated to administer the mRNA at a dose of ~25-100 ug as taught by Horhota because this is a known dosage for the administration of mRNA vaccines as taught by Horhota. Given that Ashmead teaches syringes with a volume of between 1-3 ml, such a dose of 25-100 ug of mRNA would render a concentration below 200 ug/ml when combining the prior art references.
Regarding claim 4, per the specification, “long chain” RNA is at least 100 nucleotides in length (e.g., specification at page 12, third paragraph). Horhota teaches that the RNA can be at least 100 nucleotides (e.g., claim 90 of Horhota)
Regarding claim 5, claim 5 merely recites an inherent property of the syringe of claim 1. As such, given that Ashmead teaches the recited syringe to be used with an RNA product, step (iii) of claim 5 is an inherent property of the syringe taught by Ashmead absent evidence to the contrary. Given that the structure of the syringe of Ashmead is identical to that presently recited, it is assumed that the recited characteristics are inherently present in the syringe of Ashmead with regards to step iii (see MPEP 2112, section III, for a discussion on inherent characteristics of identical products).
Regarding claim 6, Ashmead teaches that the inner surface of the syringe barrel is silicon-free (see claim 1 of Ashmead).
Regarding claim 7, Ashmead teaches that the syringe barrel can comprise cyclic olefin copolymer (COP, e.g., paragraph 65).
Regarding claim 8, Ashmead teaches that the syringe barrel can comprise glass (paragraph 65).
Regarding claim 9, Ashmead teaches that such silicon-free syringes can comprise syringe barrels made of glass, which reasonably includes a glass inner surface (i.e., “coating” or top layer, see for instance paragraph 112).
Regarding claim 10, Ashmead teaches that the syringe plunger stopper comprises a thermoplastic elastomer (paragraph 55) or rubber (paragraph 100).
Regarding claim 11, Ashmead teaches that the stopper can comprise a fluoropolymer barrier (paragraph 33). Per the present specification, a fluoropolymer is an example of a compound which reduces gliding force needed for an injection (e.g., page 14, paragraph 7 of present specification). Thus, Ashmead teaches that the stopper comprises a coating/barrier comprising a coating to reduce gliding force by teaching a stopper with fluoropolymer barrier (paragraph 33).
Regarding claim 21, Ashmead teaches that the syringes are 1-3 ml in volume (paragraph 100). Horhota teaches that mRNA vaccine doses are 25-100 ug of mRNA (e.g., paragraphs 610-611). Thus, following the teachings of Horhota with respect to known doses of mRNA vaccines (e.g., 25 ug of mRNA), using such a dose with the syringes of Ashmead would yield a concentration of, for instance, 25 ug/ml. Furthermore, Horhota teaches such mRNA formulations at concentrations below 100 ug/ ml (see Tables 3 and 20).
Regarding claim 23, the specification states that “RNA integrity” describes a complete RNA sequence with correct length present in the pharmaceutical. Given that Horhota teaches mRNA and its uses in vaccine components (e.g., paragraph 610-611), the practitioner is motivated to use RNA with a complete and correct sequence, as such mRNAs are known to be used in therapeutics such as vaccines. Furthermore, Horhota teaches mRNAs, and there is no teaching in Horhota which suggests that such mRNAs are not the correct sequence or length and therefore comprise the recited “RNA integrity.”
Regarding claim 25, Horhota teaches that the ecapsulation efficiency is desirably high, for instance close to 100% (paragraph 225). Horhota therefore teaches that there is less than 20% free RNA (paragraph 225).
Regarding claim 26, Horhota teaches that the nucleic acid can be 1,000 nucleotides in length (paragraph 390).
Regarding claim 29, Horhota teaches that the RNA can comprise pseudouridine (paragraph 402).
Regarding claim 70, these claim limitations are addressed above in the rejection of claim 1, where furthermore Ashmead teaches that the syringe is a pre-filled syringe (e.g., claim 1 of Ashmead, and see rejection of instant claim 1, above).
Regarding claim 85, Ashmead teaches the use of their syringe for the treatment of ocular disease (e.g., claim 22). A practitioner can therefore immediately envision such a method as injecting a subject with a syringe filled with a pharmaceutical composition of Ashmead, as Ashmead teaches that the syringes can be used for treating diseases (e.g., claim 22).
Regarding claim 87, claim 87 can broadly be interpreted to mean simply obtaining a filled syringe such as that recited in claim 1 and storing the syringe for a point in time. Ashmead teaches obtaining pre-filled silicon-free syringes with pharmaceuticals such as RNA (claims 1 and 3). A practitioner can immediately envision filling a syringe to obtain a pre-filled syringe and then keeping the syringe.
Response to Arguments
The Applicant’s arguments filed 6/9/2026 have been considered and are not persuasive. The Applicant argues that Horhota teaches that their methods are drawn to “concentrated” formulations, and is not directed to “low concentrations” in syringes. This argument is not persuasive because it is not an accurate representation of what Horhota actually teaches. The Applicant points to a phrase that is repeated in Horohota: “prior to in vivo dosing, particles were concentrated using centrifugal filters,” at paragraphs 699, 703, 709, and 712. As an initial matter, the word “concentrated” appears to be conflated by the Applicant to mean “higher concentrations” or high concentrations, when in fact the word “concentration” does not inherently mean that a concentration is “highly concentrated,” but can simply mean that a formulation has been made to a desired concentration. To illustrate the point that Horhota is certainly not restricted to “higher concentrations” of dosages or formulations, within the same example that the Applicant points to in paragraph 703, Table 3 is presented which shows that the mRNA is at concentrations between 51-60 ug/ml, the same mRNA concentrations presently recited in claim 1 (see Table 3, paragraph 703 of Horhota). Thus, Horhota teaches mRNA “concentrations” at those which are recited, and the word “concentrate” does not mean “highly concentrate,” but simply means to adjust the concentration of a molecule to a desired concentration for a use. To further corroborate this point, Horhota specifically teaches that mRNA vaccines are administered at a dose of 25-100 ug (paragraphs 610-611), where administering such a dose in a 1-3 ml syringe as taught by Ashmead would yield a concentration of mRNA below 200 ug/ml.
Thus, when the Applicant claims that “the entire thrust” of Horhota is aimed at high concentration doses to achieve the highest possible mRNA concentration, these arguments do not properly characterize what Horhota has actually taught, where Horhota clearly teaches effective dosages below 100 ug for mRNA vaccines (paragraphs 610-611). A practitioner of ordinary skill would understand that the important factor when considering a vaccine dosage would be, for instance, the recommended concentration of the therapeutic, and would not simply try to max out the concentration of the mRNA. The practitioner would to the contrary be guided by what dose is recommended for a therapeutic outcome. Given that Horhota teaches that mRNA vaccines are at a dose of 25-100 ug, the practitioner would understand that such a dose should be administered, and would “concentrate” their formulations to meet the parameters of a required therapeutic dose. In short, the “entire thrust” of Horhota is not to make highly concentrated mRNA formulations, and in fact not only teaches that therapeutic mRNA is administered at a dosage as presently recited, but also in fact made concentrations of mRNAs which are below 100 ug/ml (e.g., Table 3).
In response to applicant's argument that the recited syringes yield reduced agglomeration with respect to the mRNA, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In the present case, the practitioner would already be motivated to formulate mRNAs at the recited concentrations based on the motivational teachings of Horhota, who teaches that mRNA vaccines are administered at doses of 25-100 ug, where the combination of the syringes of Ashmead (1-3 ml volumes) with the mRNA formulations of Horhota would yield an mRNA at such concentrations. The practitioner is therefore already motivated to make mRNA formulations at such concentrations, where any additional advantages such as reduced agglomeration can not be the basis for patentability given that the practitioner is already motivated to make such formulations. In addition, the result of reduced aggregation or agglomeration when using syringes lacking silicone oil is not a new inventive concept because Ashmead teaches that silicone oils are known to aggregate particles, and that this is a known problem with silicone-oil containing syringes (paragraph 3). The results are therefore not surprising or unpredictable, and indeed Ashmead has developed silicone-oil free syringes in part to address the concerns of the use of silicone in syringes (see Ashmead, entre document and claims).
The Applicant makes additional arguments which reiterate the idea that Horhota requires only high concentrations of mRNA-LNP formulations, and that the combination of Ashmead and Horhota would yield only high concentrations of mRNA formulations. Again, these arguments are not persuasive, because a practitioner would understand that based on the teaching of Horhota, that mRNA vaccines are administered at a dose of 25-100 ug, the combination of Ashmead’s 1-3 ml volume syringes with Horchata’s recommended therapeutic dosage would yield mRNAs at the recited concentration (i.e., below 200 ug/ml). Horhota is simply not exclusively directed to high concertation mRNA formulations, as the Applicant argues.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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