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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 70-92, 96-98) in the reply filed on 06/26/2026 is acknowledged.
Claims 93-95, 99 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/26/2026.
Claims Status
Claims 1-69 is/are cancelled. Claims 70-99 is/are currently pending with claims 93-95 and 99 withdrawn. Claims 70-92 and 96-98 is/are under examination.
Claim Interpretation
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
Claim Objections
Claim 88 is objected to because of the following informalities:
Claim 88 recites “10 or greater nucleosides in length”. This limitation should read “10 or more nucleosides in length” for grammatical correctness.
Appropriate correction is required.35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim Rejections - 35 USC § 101
Claim 91 is rejected under 35 U.S.C. 101 because Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 91 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). Claim 91 is drawn to a cell which is optionally an isolated cell. As such, claim 91 encompasses in vivo cells. The specification teaches that cells in the context of the invention may be human cells (paragraph [00279]) and that cells comprising the RNA molecule may be cells in vivo in humans (paragraph [00136]). As such, claim 91 encompasses cells in a human organism, which are considered to form part of a human organism.
Claim Rejections - 35 USC § 112
112(b):
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 71-72, 75-77 and 92 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 71-72 and 76-77 recite “a precursor RNA” t0 which the 3’-stabilizing region of B is covalently linked. It is unclear if this precursor RNA is different from the RNA molecule of claim 70 (i.e., not comprised in the RNA molecule and not a precursor to the RNA molecule). The description of precursor RNA in the specification indicates that “A” of Formulas I and II, before being linked to “B” of Formula I, is a precursor RNA (paragraph [0011]). As such, for purposes of further examination, the precursor RNA of claims 71-72 and 76-77 is interpreted to be “A” of Formulas I and II.
Claim 75 recites the limitation "linkers (L)" in line 8. There is insufficient antecedent basis for this limitation in the claim. In line 2, “L” is shown as a separate structure from “B” in Formula II. However, lines 7-8 recite that “B” comprises “L”. It is unclear whether the “L” shown in Formula II is part of “B” and is the “L” comprised in “B”, or if the “L” in Formula II is comprised in Formula II in addition to the “L” comprised in “B”.
Claim 92 recites the limitation “comprising the RNA molecule, or comprising a cell comprising the RNA molecule, of claim 70” (lines 1-2). There is unclear antecedent basis for “the RNA molecule” in line 2. The antecedent basis of “the RNA molecule” in lines 1 and 2 would be clarified if this limitation were thus phrased: “comprising the RNA molecule of claim 70 or comprising a cell comprising the RNA molecule of claim 70”.
112(a):
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 75 and 96 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claims 75 and 96 recite structures “L” which are linkers “capable of binding a purification handle”. However, no structure is described for “L” with the exception of linkers which covalently link the RNA molecule and the purification handle (e.g., pages 78-86; paragraph [00222]). As such, the disclosure does not describe linkers which are capable of non-covalently binding a purification handle. Therefore, the disclosure does not describe a number of species representative of the full scope of the genus of linkers capable of binding to a purification handle, as no species representative of non-covalent binding are provided. The disclosure only provides species of linkers capable of covalently binding a purification handle.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 70-92, 96-98 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schlake (US 20160235864 A1), as evidenced by NCBI Reference Sequence: NC_000004.12 (2022) and Pearson (2012), in view of Grijalvo (2010).
Regarding claims 70, 75, 90, Schlake teaches a modified mRNA molecule comprising a 5’ CAP structure, a protein-coding sequence, a poly-A tail, and a 3’-stabilizing structure (claims 12, 15; paragraph [0165]). The stabilizing structure described in paragraphs [0048] and [0049], comprised in SEQ ID NO:6, comprises 50 nucleotides (it consists of approximately 168 nucleotides, see alignment between SEQ ID NO:6 and human genome Ref Seq NC_000004.12 below).
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Regarding claims 71-72, 76-77, 96, Schlake teaches that the 3’ stabilizing region is ligated to the coding sequence by a polymerase (paragraphs [0125]-[0126]).
Regarding claim 80, Schlake teaches that the 3’ stabilizing region is derived from the albumin 3’ UTR, which comprises a stem loop sequence (see paragraphs [0048]-[0049]; see Pearson, 2012, which teaches that the albumin 3’ UTR comprises a stem loop structure).
Regarding claims 81-83 and 97, Schlake teaches that one or more of the nucleotides may be modified or unmodified at the sugar or base (paragraphs [0132]-[0151]), and one or more phosphate backbone linkages may or may not be modified (paragraph [0137]).
Regarding claim 84, Schlake teaches that the modified nucleotide may be a modified uracil, cytosine, guanine, or adenine (paragraphs [0138]-[0143]).
Regarding claim 85, Schlake teaches that the modified sugar may be a deoxyribose (paragraphs [0134]-[0136]).
Regarding claims 86-87, Schlake teaches that the modified backbone linkages may be phosphorothioate linkages (paragraph [0137]).
Regarding claims 88-89, Schlake teaches that the polyA tail is at least 60 nucleotides long (claim 15).
Regarding claim 90, Schlake teaches that the RNA molecule is an mRNA molecule (claim 1).
Regarding claim 91, Schlake teaches a cell comprising the mRNA molecule (claim 7).
Regarding claim 92, Schlake teaches a pharmaceutical composition comprising the RNA molecule and a pharmaceutically acceptable carrier (claim 16).
However, Schlake does not teach that the mRNA molecule comprises a 3’-terminal lipid moiety (instant claim 70 recites a 3’-terminal purification handle, whose structure is described in claim 74 as comprising a lipid).
Grijalvo teaches that RNA oligonucleotides may comprise covalently-linked 3’-terminal lipid moieties.
Regarding claims 70, 73-75, 78-79, 96, and 98, Grijalvo teaches that RNA molecules may be modified by the addition of a 3’-terminal lipid moiety, which enhances delivery to cells (pages 6806-6807). This 3’-terminal lipid moiety may be covalently linked to the 3’ terminus of the RNA molecule, using a linker (Scheme 1; page 6807).
Schlake teaches that the mRNA molecule is delivered to cells (claim 7). As such, it would have been obvious to an artisan at the time of filing that known oligonucleotide modifications which improved delivery to cells should be incorporated in the mRNA of Schlake. As Grijalvo teaches that 3’-terminal covalently-linked lipid moieties improve cell delivery, it would have been obvious to an artisan to add the 3’-terminal lipid moiety of Grijalvo to the mRNA oligonucleotide of Schlake, thus rendering obvious claims 70, 73-75, 78-79, 96, and 98.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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