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 .
Priority
This application is a national stage entry under 35 USC 371 of PCT/US2021/032555 (filed on 5/14/2021). Acknowledgement is made of Applicant’s claim for benefit to US Provisional applications 63/030,739 (filed on 5/24/2020) and 63/025,936 (filed on 5/15/2020).
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/12/2025 is acknowledged. Claims 3-7,16-20,23,24,37, and 44-47 read on the elected species. These elections were made without traverse.
Claims 33, 40, and 42 are withdrawn from consideration.
Upon reconsideration, the restriction requirement between Groups I and II as set forth in the Office action mailed on 10/08/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or non-statutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims Status
Claims 3-7,16-20,23-24,33,37,40,42, and 44-47 are pending.
Claims 40-42 are withdrawn from consideration based on restriction election.
Claims 3-7,16-20,23-24,33,37, and 44-47 have been considered on the merits.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 3-7,16-20, 23-24,33,37, and 44-47 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3,5,16-18,20,23,27,39,43,56-59,62 of copending Application No. 17/925,125 (reference application).
Regarding claim 3: Reference claim 3 recites an article, comprising: a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle; wherein the article has a shelf-life of at least three months when stored at a temperature of greater than 0 °C and less than or equal to 10 °C; wherein the article comprises a total amount of full length RNA, and the total amount of full length RNA is greater than or equal to (1 + the fraction of the full length RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the full length RNA) x (the number of individual doses of the liquid pharmaceutical composition in the article); and wherein the RNA encodes an infectious disease antigen, wherein the infectious disease is caused by or associated with Severe Acute Respiratory Syndrome (SARS-CoV-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 3 read on and are narrower than those of instant claim 3 and therefore anticipates the claim.
Regarding claim 4: Following the discussion above, reference claim 61 recites the article of claim 3, wherein the article comprises a vial, a syringe, a cartridge, an infusion pump, and/or a light protective container.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 61 read on and are narrower than those of instant claim 4 and therefore anticipates instant claim 4.
Regarding claim 5: Following the discussion above, reference claim 5 recites the article of claim 3, wherein the total amount is greater than or equal to 1.05 x (an individual dose of the liquid pharmaceutical composition), such as greater than or equal to 1.2 x (an individual dose of the liquid pharmaceutical composition).
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 5 read on and are narrower than those of instant claim 5 and therefore anticipates instant claim 5.
Regarding claims 6 and 7: Following the discussion above, reference claim 3 recites an article, comprising: a liquid pharmaceutical composition comprising RNA formulated in a lipid nanoparticle….
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the limitations of reference claim 3 include those from claims 6 and 7 of the RNA formulated in an LNP. Therefore, instant claims 6 and 7 are anticipated.
Regarding claim 16: Following the discussion above, reference claim 16 recites the article of claim 3, wherein the RNA comprises mRNA.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 16 are narrower than those of instant claim 16 and therefore anticipates instant claim.
Regarding claims 17-18 : Following the discussion above, reference claims 17-18 recite the article of claim 3, wherein the RNA comprises greater than or equal to 400, ….nucleotides and the article of claim 3, wherein the RNA comprises less than or equal to 15,000, 14,000, 13,000, 12,000, 11,000, 10,000, 9000, 8000, 7000, or 6000 nucleotides, respectively.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claims 17-18 read on and are narrower than those of instant claims 17-18 and therefore anticipates instant claim.
Regarding claim 19 : Following the discussion above, reference claim 62 recites the article of claim 3, wherein the liquid pharmaceutical composition is formulated in an aqueous solution.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 62 reads on and are narrower than those of instant claim 19 and therefore anticipates instant claim.
Regarding claim 20 : Following the discussion above, reference claim 23 recites a pharmaceutical composition comprising mRNA encapsulated in a lipid nanoparticle, wherein the composition comprises a total amount of intact mRNA that is greater than an effective amount of intact mRNA, wherein the composition comprises at least the effective amount of the intact mRNA after storage of the composition for a period of time; and wherein the mRNA encodes an infectious disease antigen, wherein the infectious disease is caused by or associated with Severe Acute Respiratory Syndrome (SARS-CoV-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 23 read on and are narrower than those of instant claim 20 and therefore anticipates instant claim.
Regarding claim 23: Following the discussion above, reference claim 26 recites the article of claim 3, wherein the degradation is from transesterification of the full length RNA.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 26 read on and are narrower than those of instant claim 23 and therefore anticipates instant claim.
Regarding claim 24 : Following the discussion above, reference claim 27 recites the article of claim 3, wherein the degradation is greater than or equal to 5%,… of the total amount of full length RNA in the liquid pharmaceutical composition per month.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 27 read on and are narrower than those of instant claim 24 and therefore anticipates instant claim.
Regarding claim 33 : Following the discussion above, reference claim 39 recites a method of filling an article, comprising: adding RNA formulated in a lipid nanoparticle to the article to form an amount of a liquid pharmaceutical composition in the article; wherein the amount is greater than or equal to (1 + the fraction of the RNA that would degrade in the liquid pharmaceutical composition over the shelf-life of the article) x (an individual dose of the liquid pharmaceutical composition) x (the number of individual doses in the article); and wherein the RNA encodes an infectious disease antigen, wherein the infectious disease is caused by or associated with Severe Acute Respiratory Syndrome (SARS-CoV-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim read on and are narrower than those of instant claim and therefore anticipates instant claim.
Regarding claim 37: Following the discussion above, reference claim 43 recites the article of claim 3, wherein at least 40% of the total amount of full length RNA in the liquid pharmaceutical composition is full length if stored for three months at a temperature of greater than 0 °C and less than 10 °C.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 43 read on and are narrower than those of instant claim 37 and therefore anticipates instant claim.
Regarding claim 44 : Following the discussion above, reference claim 56 recites the article of claim 3, wherein the article comprises a total amount of RNA and wherein the total amount of RNA includes 40%-95% full length RNA and 5%- 60% RNA that is less than full length RNA.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 56 read on and are narrower than those of instant claim 44 and therefore anticipates instant claim.
Regarding claim 45: Following the discussion above, reference claim 57 recites the article of claim 3, wherein the total amount of full length RNA is greater than an effective amount of full length RNA, and wherein the liquid pharmaceutical composition comprises at least the effective amount of the full length RNA after storage of the liquid pharmaceutical composition for the shelf-life of the article.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 57 read on and are narrower than those of instant claim 45 and therefore anticipates instant claim.
Regarding claim 46: Following the discussion above, reference claims 58-59 recites the article of claim 3, wherein the RNA comprises greater than or equal to 4000 nucleotides and the article of claim 58, wherein the RNA comprises less than or equal to 6000 nucleotides, respectively. Reference claims 17 recites the article of claim 3, wherein the RNA comprises greater than or equal to 400, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, or 8000 nucleotides.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 17 and 58-59 read on and are narrower than those of instant claim 46 and therefore anticipates instant claim.
Regarding claim 47: Following the discussion above, reference claim 27 recites reference claim 27 recites the article of claim 3, wherein the degradation is greater than or equal to 5%, greater than or equal to 8%, greater than or equal to 9%, greater than or equal to 10%, or greater than or equal to 12% of the total amount of full length RNA in the liquid pharmaceutical composition per month.
Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of reference claim 27 read on and are narrower than those of instant claim 47 and therefore anticipates instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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