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 86-102 are pending in the present application.
Applicant’s election without traverse of the following species: (i) the specific combination of SEQ ID NO: 2 as a 5’ UTR and SEQ ID NO: 10 as a 3’ UTR; and (ii) OCT3/4 as a species of a protein, in the reply filed on 07/02/2026 is acknowledged.
Accordingly, claims 86-102 are examined on the merits herein with the above elected species.
Claim Objections
Claim 89 is objected to because of the phrase “the protein comprises….Human POU5F1”. This is because POU5F1 is the name of a gene not a protein.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 90-102 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
An engineered expression construct (EEC) comprising: (i) a 5’ UTR having the sequence as set forth in SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 38, or SEQ ID NO: 39; (ii) a 3’ UTR having the sequence as set forth in SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21; and (iii) an open reading frame that encodes a protein between the 5’ UTR and the 3’ UTR;
does not reasonably provide enablement for an engineered expression construct (EEC) as claimed broadly. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in the determination of an enabling disclosure have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art and the breadth of the claims. Ex parte Forman, (230 USPQ 546 (Bd Pat. Appl & Unt, 1986); In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988)).
When read in light of the instant specification, the sole purpose for an engineered expression construct and/or an in-vitro synthesized RNA of the present application is to increase the expression level of an encoded protein (see the title of the application; Summary of the Disclosure; and particularly at least paragraphs [0007]-[0013]). The instant specification is not enabled for the instant broadly claimed invention for the reasons discussed below.
1. The breadth of the claims
The instant claims encompass any engineered expression construct (EEC) comprising an enhancer located anywhere and/or in any orientation in the expression construct as long as the enhancer consists of the sequence CAUACUCA (an RNA sequence due to the presence of U nucleotide bases). Claim 98 encompasses an enhancer consisting of the sequence CAUACUCA in addition to the 5’ UTR having SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 38, or SEQ ID NO: 39 in an engineered expression construction; whereas claim 100 also encompasses an enhancer consisting of the sequence CAUACUCA in addition to the specific recited pairs of 5’ UTR and 3’ UTR.
2. The state and the unpredictability of the prior art
Before the effective filing date of the present application (02/25/2021), virtually nothing was known about the use an enhancer consisting of the CAUACUCA sequence in any engineered expression construct, let alone one that increases the expression level of an encoded protein as evidenced at least by the teachings of Trainor et al (Scientific Reports 11:2461; doi.org/10.1038/s41598-021-82025-6, 18 pages, 2021), Bancel et al (US 10,772,975; IDS), Xiao et al (WO 2019/080538; IDS), Theb et al (WO 2009/127230; IDS), and Suzuki (US 2006/0166913; IDS). The physiological art is recognized as unpredictable (MPEP 2164.03).
3. The amount of direction or guidance provided
Apart from disclosing an engineered 5’ UTR comprising from 5’ to 3’ direction: the mini-T7 promoter sequence of GGGAGA, the translational enhancer sequence of CAUACUCA and the Kozak sequence of GCCRCC, wherein R is A or G (SEQ ID NOs. 2-3, respectively); and wherein the engineered 5’ UTR is operably linked in 5’ to 3’ direction to a start codon, an open reading frame that encodes a protein, and a 3’ UTR that resulted in increased expression of the protein in a variety of cell types (see at least Summary of the Disclosure; Fig. 1 and Examples 1-7); the instant specification failed to provide sufficient guidance for an ordinary skilled artisan on how to make and use the translational enhancer sequence of CAUACUCA at any other location and/or in any other orientation in an engineered expression construct as claimed broadly. There is no evidence of record indicating that the translational enhancer sequence is functional (e.g., enhancing or increasing translation and/or expression of an encoded protein) if it is placed 5’ of the mini-T7 promoter sequence of GGGAGA and/or 3’ of the Kozak sequence of GCRCC in an engineered 5’ UTR, let alone that the translational enhancer sequence is incorporated at any non-5’ UTR locations (e.g., in a 3’-UTR and/or within a 3’-UTR) as encompassed broadly the instant claims. There is also no evidence of record indicating or suggesting that the enhancer sequence of CAUACUCA is also functional when it is paired with any promoter sequence other than the mini-T7 hexamer GGGAGA and/or any Kozak sequence of any length other than the disclosed GCCRCC with R is A or G. Moreover, there is also no evidence of record that the translational enhancer sequence of CAUACUCA is functional when it is placed in a reverse orientation at any location on an engineered expression construct.
Since the prior art before the effective filing date of the present application failed to provide sufficient guidance to the aforementioned issues, it is incumbent upon the present application to do so. Given the state of the prior art, coupled with the lack of sufficient guidance provided by the present application, it would have required undue experimentation for a skilled artisan to make and use the instant invention as claimed broadly.
As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires:
That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.
Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maizel.).
Accordingly, due to the lack of sufficient guidance provided by the specification to the issues set forth above, the state and unpredictability of the relevant art, and the breadth of the instant claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention.
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 86-102 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 136-155 of copending Application No. 18/840,727 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because a method comprising: contacting somatic cells with a reprogramming factor (RF) for a time that results in formation of colonies of induced pluripotent stem cells (iPSC); and bulk passaging a subset of the iPSC; the same method wherein the RF comprises synthetic RNA (claim 142), or the RF comprises Oct4, Sox2, KLf4, Nanog, Myc, SV40Tag, or Lin28 (claim 143), or the RF comprises an expression construct encoding a reprogramming gene operably linked to regulatory elements comprising a 5’ UTR comprising a T7 minimal promoter, a mini-enhancer having the sequence CAUACUCA, and the Kozak sequence comprising the sequence GCCACC or GCCGCC (claims 144-145), preferably the 5’ UTR comprising the sequence of SEQ ID NO: 1 that is 100% identical to SEQ ID NO: 2 of the present application and a 3’ UTR comprising a spacer and a stem loop structure (claim 146), including the 3’ UTR comprising the sequence of SEQ ID NO: 34 that is 100% identical to SEQ ID NO: 10 of the present application (claim 148) in claims 136-155 of copending Application No. 18/840,727 encompasses synthetic RNA that is identical or substantially identical to an in vitro-synthesized RNA and an engineered expression construct in the application being examined and, therefore, a patent to the genus would, necessarily, extend the rights of the species or sub- should the genus issue as a patent after the species of sub-genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusions
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/
Primary Examiner, Art Unit 1631
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