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 .
Claims Status
Claims 3-7,16-20,23-24,33,37, and 44-47 are pending.
Claims 3-7,16-20,23-24,33,37, and 44-47 have been considered on the merits.
Status of Rejections/Response to Arguments
RE: Rejection of claims 3-7,16-20,23-24,33,37, and 44-47 under 35 U.S.C. 103 over Brader et al (WO2018089540).
Regarding claims 3, 20, and 33, Applicants have traversed the rejection of record on the following grounds:
That the primary reference Brader et al does not teach pharmaceutical composition such that the equation found in claim 3 is rendered obvious because the equation “ensures that the article contains a total amount of full length RNA such that at the end of the shelf-life of the article there will remain at least an individual dose of the full length RNA.” ( Remarks p2).
That determining the volume of a formulation that is needed to obtain a dose of mRNA to be administered to a subject, and loading a vial with this pre-determined dose volume, does not result in article of claim 3.
In response, these arguments are not persuasive.
Applicants argue that the equation of claim 3 offers an amount of the composition in the article that allows for an amount of RNA to be equal to an at least an individual dose at the end of the shelf life. However, Brader et al does teach that a unit dosage includes enough of the active ingredient, mRNA LNP, and a convenient fraction of such dosage, such as one half or a third (See, ¶00467). The active ingredient is an LNP with full length mRNA in this case, therefore a dosage with LNP with full length mRNA and a fraction of that dosage added is equivalent to the limitation of claim 3, as no matter what the original dosage is an extra amount of the active ingredient which would be LNP with mRNA is included per dose, the reasoning for it, whether it is to cover degradation over shelf-life or any other reason, the extra RNA is present in the composition within the article.
Regarding the volume of the formulation argument, having the individual dose volume, allows one of ordinary skill in the art to understand how much mRNA is needed per dosage to then have an article that can contain multiple dosages with extra added to cover degradation over shelf-life or since Brader et al teaches that dosage can include a fraction more, it can be conclude the volume includes full mRNA with a fraction more and only the number of the additional doses needs to be calculated by a person having ordinary skill in the art to arrive at the article of claim 3.
Therefore, the rejection is maintained over claims 3-7,16-20,23-24,33,37, and 44-47.
RE: Non Statutory Double Patenting rejection of claims 3-7,16-20,23-24,33,37, and 44-47 provisionally rejection over co-pending application 17/925,125 claims 3,5,16-18,20,23,27,39,43,56-59, AND 62
Applicants have overcome this rejection due to Applicant filing a terminal disclaimer over Application No. 17/925,125, that has been accepted on 06/12/2026.
Therefore, this rejection has been withdrawn.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 3-7,16-20,23-24,33,37,44-47 are rejected under 35 U.S.C. 103 as being unpatentable over Brader et al (WO 2018/089540 A1; cited in IDS filed 4/27/2023).
Brader et al discloses a lipid nanoparticle (LNP) formulation, such that the LNP include therapeutics such as RNA, and delivery to regulate polypeptide, protein or gene expression. They also disclose manufacturing LNP formulations (See, Abstract).
Regarding claim 3-5, 6-7, and 16: Brader et al teaches a stabilized LNP formulation comprising of a plurality of LNPs and a stabilizing agent that mitigates the degradation of LNPs or subpopulation. The LNP formulation (either liquid or lyophilized) that is stored at about 4 °C or higher (See, ¶00139). Brader et al teaches that a pharmaceutical composition in accordance with the present disclosure may be prepared, packaged, and or sold in bulk as a single unit dose, and or as a plurality of single unit doses (See, ¶00467). Brader et al teaches that storage refers to storing the disclosed LNP formulation product either in its final state or in-process state before final packing and the modes of storage include vials and syringes (See, ¶00140).
Therefore, Brader et al teaches a liquid pharmaceutical composition comprising RNA formulated in an LPN. The liquid is necessarily provided in a vial or container, the vial or container reads on an article that contains the formulation.
Brader et al teaches that one embodiment, the formulation is stable at temperatures from about 2°C to 8°C for at least 2 months (See, ¶00159). Brader et al further teaches that there is a particular embodiment where the formulation disclosed is stabilized at a temperature ranging between -20°C and 4°C at a nucleic concentration (e.g. an mRNA concentration) of up to 2 mg/mL for at least 12 weeks (3 months) (See, ¶00161).
Therefore, Brader et al teaches an article…wherein the article has a shelf-life of at least three months when stored at greater than 0°C and less than or equal to 10°C.
Brader et al teaches that the amount of therapeutic (e.g. RNA, mRNA) in a LNP may depend on the size, composition, desired target and or application of the LNP, as well as the properties of the therapeutic. They further teach that amount of RNA useful in a LNP may depend on size, sequence, and other characteristics of the RNA and relative amounts of the therapeutic, along with other elements in the LNP may vary (See, ¶00450). It is also taught that a unit dose is discrete amount of the pharmaceutical compositions comprising a predetermined amount of the LNP (active ingredient) and the it is equal to the dosage of the active ingredient which would be administered to a subject and or a convenient fraction of such as dosage such as, one half or one third of such a dosage (See, ¶00467).
Brader et al differs from the claims in that the limitation wherein the article comprises a total amount of RNA and the equation associated with this limitation in claim 3 and 5.
However, each of these differences are considered prima facie obvious, as the limitation about the total amount of RNA and the equation found in claims 3 and 5, the claims are requiring a product with X amount of RNA based on the equation in the claim. Brader et al renders this obvious because it teaches a formulation with 2 mg/mL in a vial stored (See, ¶00161). One of ordinary skill of the art can work backwards to fill in the equation such that the values are less than or equal to 2mg/mL depending on the dose of individual full length RNA. Brader et al also provides motivation to optimize the RNA content in the invention. Therefore, it would have been obvious to formulate the product in the article to account for dosage, number of doses and degradation to achieve an amount to be in an article of LNP with RNA. As such, determining the total amount of RNA would have been a matter of routine optimization. See MPEP 2144.05.
The limitation of claims 4-7, and 16 include those from claim 3, it is included in the rejections stated above and is read on by the motivation set forth by Brader et al to optimize the concentration of RNA, to utilize mRNA for the LNP formulation in the article, and for the article to be a vial or syringe.
Regarding claims 17-18 and 46: Following the discussion above, in relation to the length of the polynucleotides that can be employed in the LNP, Brader et al teaches that there are embodiments with the polynucleotide can be greater than at least 400 nucleotides in length all the way to at least 5000 nucleotides or greater than 5000 nucleotides (See, ¶00299). Brader et al teaches that the amount of therapeutic (e.g. RNA, mRNA) in a LNP may depend on the size, composition, desired target and or application of the LNP, as well as the properties of the therapeutic. They further teach that amount of RNA useful in a LNP may depend on size, sequence, and other characteristics of the RNA and relative amounts of the therapeutic, along with other elements in the LNP may vary (See, ¶00450). Therefore, Brader et al teaches a range of nucleotides for the RNA in the invention that encompasses the claimed range, and provides motivation to optimize the LNP formulation in an article such that routine optimization by one having ordinary skill in the art based on specifics of the needs of the formulation components is to be expected. As such, determining the number of nucleotides would have been a matter of routine optimization (See, MPEP 2144.05).
Regarding claim 19: Following the discussion above, Brader et al teaches a pharmaceutical composition may be prepared in a variety of forms suitable for a variety of routes and methods of administrations, including liquid dosage forms, injectable forms and other routes (See, ¶00468). Brader et al teaches that the stabilized LNP formulation disclosed may have the feature of being an aqueous or frozen formulation (See, ¶0006). This reads on the limitation of claim 19, “ wherein the liquid pharmaceutical composition is formulated in an aqueous solution.”
Regarding claim 20: Following the discussion above, Brader et al teaches that a pharmaceutical composition in accordance with the present disclosure may be prepared, packaged, and or sold in bulk as a single unit dose, and or as a plurality of single unit doses (See, ¶00467). The limitation of claim 20 is included in those from claim 3, it is included in the rejections stated above and reads on, “ a pharmaceutical composition…”.
Regarding claim 23,24,44,47: Following the discussion above, the amount of RNA in the article of claim 3, the degradation of the RNA of the formulation in the article does not change the product itself. The type of degradation, i.e. transesterification, and the percentage of the degradation within the article has no patentable weight as a limitation. The limitation of claims 23,24,44, and 47 include those from claim 3, it is included in the rejections stated above and is read on by the disclosures of Brader et al.
Regarding claim 33: Following the discussion above, Brader et al teaches that storage refers to storing the disclosed LNP formulation product either in its final state or in-process state before final packing and the modes of storage include vials and syringes (See, ¶00140). The method disclosed in Brader et al reads on the method of filling an article comprising of… because the method of filling an article with any amount of liquid pharmaceutical composition is implicit in the teachings of Brader et al based on the description of the packaging and storing of the formulations in vials and syringes.
Regarding claims 37 and 45: Following the discussion above about the amount of RNA in the article of claim 3, the limitation of claims 37 and 45 are included in the rejections stated above and is read on by the disclosure of Brader et al.
Therefore, claims 3-7,16-20,23-24,33,37,44-47 are rejected as being rendered obvious by Brader et al.
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 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 Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 3:00pm M-F.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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