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 the invention of Group I, drawn to a chemically-synthesized RNA having the formula of Formula I (claims 1-31 and 36-39), and of the species 5’-OH (Group A) and the species poly(A) tail (Group B) in the reply filed on 11/25/2025 is acknowledged. However, the species election requirement of Group A (element “W” of formula 1) has been withdrawn.
Claims 32-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim; based on the species elected, the only general formulas of claim 2 which are encompassed are (2), (5), (8), (11), (14), (17), (20), (23), (26), (29), (32), (35), (38), (41), (44), (47), (50), (53), (56), and (59). As claim 3 does not encompass any of these formulas of claim 2, and instead is drawn to formulas (3), (15), (39), (51), and (58), claim 3 is considered to be drawn only to nonelected species. Election was made without traverse in the reply filed on 11/25/2025.
Claims Status
Claims 1-39 is/are currently pending with claims 3 and 32-35 withdrawn. Claims 1-2, 4-31, and 36-39 is/are under examination.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Figures 3A, 3B, 4, 6A, 6B, 6C, 7A, 7B, 7C, 7D, 7E, 7F, and 7G are color drawings.
Information Disclosure Statement
The information disclosure statement filed 12/15/2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. No copy has been filed of NPL#8 as listed in the IDS.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Hyperlinks were found on page 14 line 18 and page 15 line 23. Applicant is advised to review the specification in order to ensure that all hyperlinks are identified and appropriately removed.
Claim Interpretation
Claims 31 and 36-39 recite intended uses of the claimed RNA of claims 1 and 19. According to MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. The intended uses recited in claims 31 and 36-39 do not appear to impart any structure to the claimed product. Therefore for the purpose of this action, claims 31 and 36-39 are directed to the claimed RNA structures of claims 1 (claims 31, 36-37, 39) and 19 (claim 38).
Claim 23 requires a first RNA of length n and a second RNA of length n-1, wherein the second RNA is at least 95% identical to the first RNA. While claim 23 does not specify a range of values for n, in order for any RNA to fulfill the percent identity requirements, n must be greater than or equal to 20 nucleotides.
Claim 24 requires a first RNA of length n and a second RNA of length n-2, wherein the second RNA is at least 93% identical to the first RNA. While claim 24 does not specify a range of values for n, in order for any RNA to fulfill the percent identity requirements, n must be greater than 28 nucleotides.
Claim 25 requires a first RNA of length n and a second RNA of length n-3, wherein the second RNA is at least 90% identical to the first RNA. While claim 25 does not specify a range of values for n, in order for any RNA to fulfill the percent identity requirements, n must be greater than or equal to 30 nucleotides.
Claim Objections
Claims 22-25 and 29 are objected to because of the following informalities:
Claims 22 and 23 recite “A RNA”. “A RNA” should be amended to “An RNA”, as “RNA”, when spoken, begins with a vowel sound.
Claims 23-25 recite that “the percentage of identity of the chemical composition of the RNA of length [(n-1)/(n-2)/(n-3)] to the chemical composition of the [full length] RNA of length [n] is [based on/meant with respect to] the chemical composition of the [(n-1)/(n-2)/(n-3)] nucleotides of the full length RNA of length n” (in square brackets are variations of similar or equivalent phrasing between claims). This language is redundant, as the phrasing that x sequence is at least y% identical to z sequence already requires the specific direction of comparison (i.e., this and equivalent phrasing requires that x sequence be compared to z sequence) (e.g., in claim 23, “[an] RNA having a chemical composition being at least 95%...identical to the chemical composition of the RNA”, lines 2-5). The examiner suggests removing the phrasing objected to above for clarity and simplicity.
Claim 29 recites an “infections agent”, referring to the “infectious agent” of claim 28. The term “infections agent” in claim 29 should be amended to “infectious agent”.
Appropriate correction is required.
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 8-12, 14-15, 19, 22-25 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.
Regarding claims 8-12, 14-15, and 22-25, the phrases "preferably", “more preferably”, “still more preferred”, and “even more preferred” render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Claim 19 recites the limitation "the non-cancer wildtype" in line 3. There is insufficient antecedent basis for this limitation in the claim. A non-cancer wildtype peptide had not previously been recited in the claims. While the juxtaposition of “the cancer peptide” (line 1) and “the non-cancer wildtype” (line 3) implies that “the non-cancer wildtype” is a single specific variant of “the cancer peptide”, it is well-known in the art that genes are often polymorphic, with multiple different, naturally-occurring, benign polymorphisms. As no specific peptide is described or required, “cancer peptide” encompasses peptides with more than one benign wildtype variant. Amendment of “the non-cancer wildtype” to “a non-cancer wildtype” would rectify the lack of antecedent basis and the lack of clarity regarding the number of wildtype variants encompassed for each “cancer peptide”.
Claims 23-25 recite an “RNA population comprising…at least 1% of [an] RNA” (lines 1-3 of claim 23, lines 1-2 of claims 24-25). It is unclear what “1% of [an] RNA” means, as the claim does not describe whether this refers to 1% of the mass of the RNA, the nucleotide sequence, or another parameter of the RNA. The broadest reasonable interpretation of claims 23-25 is that the RNA population comprises at least 1 nucleotide derived from an RNA, wherein the full-length RNA is at least 95% (claim 23), 93% (claim 24), or 90% (claim 25) identical to an RNA.
Claims 23-25 recite the limitation "the RNA" and “the full-length RNA” in lines 5 (claim 23), 7 (claim 23), 7-8 (claim 23), 9 (claim 23), 4 (claim 24), 6 (claim 24), 6-7 (claim 24), 8 (claim 24), 4-5 (claim 25), 6 (claim 25), 7 (claim 25), 8 (claim 25). There is insufficient antecedent basis for this limitation in the claim. Claims 23-25 depend on claim 22, which recites “the RNA according to claim 1”. However, claims 23-25 also recite that the RNA population comprises “1% of [an] RNA” (lines 2-3 claim 23, lines 1-2 claim 24, line 2 claim 25). It is unclear which of these RNAs is referred to by subsequent recitations of “the RNA” or “the full-length RNA” in claims 23-25.
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 1-2, 4-31, 36-39 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.")."
Claim 1 recites that the chemically synthesized RNA can comprise a 5’-Cap or “chemically modified analogues of said 5’-Cap” (lines 5-8). The specification, however, does not describe the chemical structure of the 5’-Cap required by claim 1, and does not describe the chemical structures of chemically modified analogues of the 5’-Cap, 5’-triphosphate group, 5’-disphosphate group, or 5’-monophosphate group. The only species of 5’-Cap described by the specification is N7-methylguanosine triphosphate (page 4 line 27; page 18 line 28 “Cap 5n UTR: 5’-N7-MeGppp”). Because the disclosure does not provide a definition of a 5’-Cap, and a 5’-Cap is not described as only being N7-methylguanosine triphosphate, an artisan would not be able to determine whether N7-methylguanosine triphosphate was representative of the full scope of the genus of 5’-Cap structures. An artisan would not be able to determine what chemical structures are encompassed by the limitations “5’-Cap” and “chemically modified analogues of said 5’-Cap”, and said artisan would not be able to determine that the applicants were in possession of chemically-modified analogues of a 5’-Cap, a 5’-disphosphate group, a 5’-monophosphate group, or a 5’-triphosphate group. Claim 2 sufficiently further limits the structure of the “W” structure of Formula (1) to an -OH group, a free triphosphate group, a free diphosphate group, a free monophosphate group, and N7-methylguanosine triphosphate (N7MeGppp). Claims 15-31 and 36-39 depend on claim 1 but do not sufficiently further limit or describe the structure of the “W” group species of Formula (1), and thus are rejected for lacking sufficient written description.
Claim 1 recites that the chemically-synthesized RNA comprises a 5’UTR and a 3’UTR. However, the only further description of the sequence of either UTR is that a UTR has a length of 2-5 nucleotides (claim 5), comprises the sequence AAG (claim 6), and consists of the sequence ACAAG (claim 7). The specification states that ACAAG is a “preferred 5’UTR sequence” (page 5 lines 26-27). The specification also states that the 5’UTR preferably does not exceed 10 nucleotides in length and preferably is “disclosed in Elfakess and Dikstein (2008) PLoS ONE 3 (8), e3094” or “disclosed in WO 2017/167910 A1” or consists of the sequence CNGCCACC (page 5 line 16-page 6 line 10). These definitions of a 5’UTR are not limiting, as they are stated to be preferable, but not required, qualities and structures. As such, UTR sequences encompassed by the breadth of claim 1 are not limited to the sequences ACAAG, AAG, or CNGCCACC, or the sequences of Elfakess (provided herein) or WO2017167910A1 (of record), or to the length limitation of 10 or fewer nucleotides. A UTR is any untranslated region of a nucleic acid sequence. As such, there are innumerable possible sequences, of any combination of nucleotides and of any length, which can be classified as UTRs. UTR sequences consisting of 2-5 nucleotides, comprising the sequence AAG, or consisting of the sequence ACAAG are not representative of the full scope of the genus of UTR sequences encompassed by the breadth of claim 1. Claims 4-6 further limit the structure of a UTR, but not sufficiently as to render the described UTR sequences representative of the UTR sequences of claims 4-6. Claims 4-6, 8-31, 36-39 depend on claim 1 but do not sufficiently further limit the structure of a UTR, and thus read on a genus of UTR sequences whose breadth is not sufficiently described by the present disclosure.
Claim 15 recites that the RNA comprises “at least one chemical modification” (line 2). The specification states that “[the] chemical modification may be at the phosphate, the ribose or the base moiety of the nucleotide” and “can be introduced during chemical synthesis or added on the ChemRNA by enzymes, for example from the families of methylases and deaminases”, a “preferred example of an enzymatic modification is the addition of a poly(A) tail (page 9 lines 4-19). One provided example of a structure of a chemical modification is a polyA tail; however, the specification states that this is a “preferred example”, not a limiting definition. The only other species of chemical modifications are provided on page 10 of the specification; however, these modifications are described as “preferred modifications”, and thus the invention is not limited to these chemical modifications. The limited number of species of chemical modifications is not representative of the entire genus of possible chemical modifications of a nucleotide. As such, an artisan would not be able to determine that the applicants were in possession of the full scope of the genus of chemical modifications of a nucleic acid.
Claim 17 recites the limitation that the coding sequenced comprised in the RNA “encodes a peptide of an infectious agent or a cancer peptide or a peptide of a tissue recognized by autoimmune cells”; claim 18 further limits the infectious agent to be “selected from viruses, bacteria and fungi”. Claim 1, on which claim 17 depends, encompasses any embodiment of coding sequence, including any required by the limitations of dependent claims 17 and 18. Moreover, claims dependent on claim 1 (2, 4-16, 19-31, 36-39) also encompass any embodiment of coding sequence. Claim 28 recites that “the coding sequence encodes a peptide of an infectious agent”, and claim 27, as a broad claim on which claim 28 depends, encompasses any embodiment of coding sequence, including the peptide of an infectious agent as required by dependent claim 28. The specification does not describe any particular peptides or infectious agents which can be used in the claimed invention. The genera of viruses, bacteria, and fungi are enormous genera comprising a wide diversity of species. With no species described in the present disclosure, the disclosure is considered to not sufficiently describe these genera of infectious agents. The genus of cancer also comprises a wide diversity of types of cancers, each with a different proteomic, transcriptomic, and genomic profile. Moreover, the term “cancer peptide” is not specifically defined, and can be broadly interpreted to encompass any peptide expressed in any cancer, regardless of the pathogenicity of the peptide. With no species of cancer or cancer peptide described in the present disclosure, the disclosure is considered to not sufficiently describe the broad genus of cancer peptides. The genus of peptides of a tissue recognized by autoimmune cells is, like the genus of cancer peptides, not specifically defined and can be broadly interpreted to encompass any peptide expressed in any tissue recognized by any autoimmune cell, regardless of pathogenicity or disease relevance of the peptide. The specification does not provide any species of peptides expressed in tissues recognized by any autoimmune cell. As such, the specification does not sufficiently describe the genus of peptides of a tissue recognized by autoimmune cells. Claims 1, 17-18, and 27-29 are rejected for lacking sufficient written description for the genus of coding sequences, including the genera of peptides of an infectious agent, cancer peptides, and peptides of tissues recognized by autoimmune cells.
Claim 29 is drawn to a vaccine comprising the RNA of claim 1; however, the claim does not specify what disease or condition said vaccine prevents. The common definition of “vaccine” is “any preventive preparation used to stimulate the body’s immune response against a specific disease, using either messenger RNA or killed or weakened bacteria or viruses to prepare the body to recognize a disease and produce antibodies” (see Dictionary.com “vaccine”, provided herein). Claim 31 recites that the RNA can be used “as a medicament”, with no specification as to what specific diseases or conditions said RNA can be used as a medicament for. Claims 36-38 recite that the RNA is used “in the treatment of cancer and tumors” (claims 36 and 38) and as a “vaccination of a cancer patient against the cancer the patient is suffering from” (claim 37). Claim 39 recites that the RNA is used “in the treatment and/or prevention of infectious diseases”, with no specification as to specific infectious diseases which can be treated using a composition comprising the claimed RNA. On pages 14-15, the specification states that the “vaccines according to the invention are suitable for the treatment of cancers and tumors” and “may be furthermore employed against infectious diseases”, including but not limited to HIV, hepatitis A, B, or C, herpes, herpes zoster, rubella, yellow fever, “dengue etc.”, flaviviruses, influenza viruses, coronaviruses, hemorrhagic infectious diseases, bacterial infectious diseases, protozoan diseases, or fungal infections. However, the specification does not provide specific structures, in particular specific coding sequences of the claimed RNA, which can be used to vaccinate against or treat specific cancers, tumors, viruses, bacteria, protozoa, or fungi. An artisan would need to perform further experimentation in order to determine a suitable RNA structure (e.g., a suitable coding sequence of the claimed RNA) for a vaccine targeting any of the cancers, tumors, viruses, bacteria, protozoa, or fungi taught in the specification or broadly encompassed by the pending claims, and such an artisan would recognize that each specific disease would require a different RNA structure or different combination of RNA structures. As the disclosure does not provide a number of species of peptides encoded by the coding sequence of the claimed RNA which is representative of the entire genus of RNA-encoded peptides which could be used in methods of treating or preventing the broad genus of cancers, tumors, viral infections, bacterial infections, protozoan infections, and fungal infections, an artisan would not be able to conclude that the applicants were in possession of the full scope of the genus of RNA molecules for use as vaccines or medicaments for any condition or agent, or for use in the treatment of any cancers or tumors, or for the treatment or prevention of any infectious diseases. Thus claims 30-31 and 36-39 lack sufficient written description. As claims 31, 36-37, and 39 are drawn to the RNA of claim 1, and claim 38 is drawn to the RNA of claim 19, reciting intended uses of the RNAs of claims 1 and 19 with no further structural limitations, claims 1 and 19 are considered to encompass the RNA structures of claims 31 and 36-39 which have the recited intended uses which lack sufficient written description. As a result, claims 1 and 19 are also rejected for lacking sufficient written description. Claims 2 and 4-29 depend on claims 1 and 19 and do not further limit the RNA such that the intended uses of claims 30-31 and 36-39 are sufficiently described, and thus claims 2 and 4-29 are also rejected for lacking sufficient written description of the RNA structures required for the claimed intended uses.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 15-28, 30-31, 36-39 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schlake (WO 2019077001 A1, of record).
Regarding claim 1, Schlake teaches a chemically-synthesized RNA (an artificial nucleic acid molecule) comprising from 5’ to 3’: a 5’-Cap, a 5’UTR element, a coding sequence, a 3’UTR element, and a poly(A) tail (claims 1, 10, 19, 30). Schlake also teaches that the coding sequence comprises a start codon at the 5’ end and a stop codon at the 3’ end (pages 4, 10, 18, 34). Thus, Schlake teaches an RNA of claimed formula (1), wherein W is a 5’-Cap, X is a 5’UTR sequence, Y is a start codon, and Z is a stop codon linked via a 3’UTR sequence to a poly(A) tail.
Regarding claim 15, Schlake teaches that the RNA comprises at least one chemical modification (claim 22).
Regarding claim 16, Schlake teaches that the RNA is modified enzymatically (page 105, the polyadenylation signal is added enzymatically, the RNA can be methylated by 2’-O-Methyltransferase).
Regarding claim 17, Schlake teaches that the RNA coding sequence encodes a tumor antigen, pathogenic antigen, autoantigen, alloantigen, or allergenic antigen peptide (page 56).
Regarding claim 18, Schlake teaches that the “term ‘pathogenic antigen’ refers to antigenic (poly-)peptides or proteins derived from or associated with pathogens, i.e. viruses, microorganisms, or other substances causing infection and typically disease, including, besides viruses, bacteria, protozoa or fungi” (page 57).
Regarding claim 19, Schlake teaches that the tumor antigen peptide comprises a tumor-specific mutation (page 56).
Regarding claim 20, Schlake teaches that the coding sequence of the RNA is expressed by cells comprising the RNA (page 29).
Regarding claim 21, Schlake teaches that the RNA is single-stranded (page 90).
Regarding claim 22, Schlake teaches a population of RNA wherein 100% of the RNA comprised in the RNA population is the artificial RNA (page 164).
Regarding claims 23-25, Schlake teaches a composition comprising “a plurality of at least two artificial nucleic acid (RNA) molecules as described herein” (page 140). Schlake also teaches that the different components of the RNA may be of a range of lengths (pages 9, 11, 55, 89). As the two RNA molecules of the composition can differ by any means by which Schlake teaches the RNA molecules may differ, the at least two artificial RNA molecules of the composition may differ by length, including by 1, 2, or 3 nucleotides.
Regarding claim 26, Schlake teaches that the RNA is comprised in a pharmaceutical composition (page 137).
Regarding claim 27, Schlake teaches that the RNA coding region may encode a protein “capable of mediating a desired diagnostic…effect, preferably resulting in detection…of a disease” (page 35). Schlake also teaches kits comprising the RNA (pages 52, 137). Schlake thus teaches kits comprising RNA which can be used for diagnostic purposes, for the detection of a disease, thus teaching diagnostic kits.
Regarding claim 28, Schlake teaches that the RNA coding sequence encodes a pathogenic antigen, which is derived from an infectious pathogen (pages 35, 56-57).
Regarding claim 30, Schlake teaches a vaccine comprising the RNA (claims 33, 37).
Regarding claim 31, Schlake teaches that the RNA can be used as a medicament (page 152; claim 46).
Regarding claims 36-38, Schlake teaches that the RNA can be used in the treatment of cancer (claim 47), wherein a patient in need thereof is administered the vaccine comprising the RNA (claim 48).
Regarding claim 39, Schlake teaches that the RNA can be used in the treatment or prevention of infectious diseases (claim 47).
Claim(s) 1-2, 4-8, 11-15, 17-20, 22-28, 30-31, 39 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schnee (WO 2015024665 A1, of record).
Regarding claims 1-2 and 13, Schnee teaches an RNA consisting of the following sequence: m7GpppN (i.e., N7-methylguanine-triphosphate, or N7MeGppp) – UTR (optional) – AUG (start codon) – coding sequence – stop codon – polyA (claims 1, 4, 17; pages 10, 15-16) (teaching formulae 2, 8).
Regarding claims 4-5, Schnee teaches that the 5’ UTR comprises at least 9 nucleotides (page 36, a fragment comprising at least 20% of the length of a full-length 5’ UTR, wherein 20% of 42, the length of SEQ ID NO:16, is 8.4).
Regarding claims 6-7, these claims further limit an optional limitation of claims 2 and 4 (in claim 4, “if present, the UTR has a length of from 2 to 10 nt”, emphasis added). As claims 6-7 are merely optional, Schnee is not required to teach the limitations of claims 6-7.
Regarding claims 8, Schnee teaches that the poly(A) tail comprises a sequence of at least 23 adenosine nucleotides (page 47).
Regarding claims 11-12, Schnee teaches that the coding sequence may encode a fragment of an antigenic peptide or protein (claim 1), wherein the fragment is at least 5 amino acids long (page 11).
Regarding claim 14, Schnee teaches that the RNA can be less than 200 nucleotides long. The 5’-Cap m7GpppN is one nucleotide long; the coding sequence is at minimum 21 nucleotides long (3-nucleotide-long start codon, 15 nucleotides to encode a 5-amino-acid-long peptide fragment, 3-nucleotide-long stop codon); the poly(A) tail is at least 23 nucleotides long (see above, claims 1, 4, 17, and pages 10-11, 15-16, 36, 47). The length of this minimum sequence is 45 nucleotides.
Regarding claim 15, Schnee teaches that the RNA backbone may be chemically modified (pages 14, 49-50).
Regarding claims 17-18, Schnee teaches that the coding sequence encodes a peptide or peptide fragment derived from a viral infectious agent (rabies) (claim 1).
Regarding claim 19, claim 19 further limits an optional limitation of claim 17 (a cancer peptide) but does not require that the coding sequence encodes a cancer peptide. As such, claim 19 is considered optional and Schnee is considered to encompass claim 19 insofar as claim 19 is optional.
Regarding claim 20, Schnee teaches that cells comprising the RNA express the encoded peptide (page 76).
Regarding claims 22-25, Schnee teaches compositions comprising one or more of the RNA sequences, encompassing compositions wherein the different RNA sequences differ by any means, including length of the 5’-Cap, 5’-UTR, coding sequence, or poly(A) sequence, each of which Schnee teaches can be of a wide range of different lengths and sequences (claim 24, teaching the composition; claims 1, 4, 17; pages 10-11, 15-16, 36, 47, teaching different lengths and sequences of the different components).
Regarding claim 26, Schnee teaches a pharmaceutical composition comprising the RNA (claim 25).
Regarding claim 27, Schnee teaches that the RNA may be used for diagnostic methods (pages 76-77), and teaches kits comprising the RNA (claim 28).
Regarding claim 28, Schnee teaches that the coding sequence encodes a peptide of an infectious agent (claim 1).
Regarding claims 30-31 and 39, Schnee teaches that the RNA can be used as a medicament (claims 29-30) or a vaccine (page 1), for use in the treatment or prevention of an infectious disease (claims 29-30).
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.
Claim(s) 1-2, 4-28, 30-31, 36-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schnee (WO 2015024665 A1, of record), in view of Schlake (WO 2019077001 A1, of record).
Regarding claims 1-2 and 13, Schnee teaches an RNA consisting of the following sequence: m7GpppN (i.e., N7-methylguanine-triphosphate, or N7MeGppp) – UTR (optional) – AUG (start codon) – coding sequence – stop codon – polyA (claims 1, 4, 17; pages 10, 15-16) (teaching formulae 2, 8).
Regarding claims 4-5, Schnee teaches that the 5’ UTR comprises at least 9 nucleotides (page 36, a fragment comprising at least 20% of the length of a full-length 5’ UTR, wherein 20% of 42, the length of SEQ ID NO:16, is 8.4).
Regarding claims 6-7, these claims further limit an optional limitation of claims 2 and 4 (in claim 4, “if present, the UTR has a length of from 2 to 10 nt”, emphasis added). As claims 6-7 are merely optional, Schnee is not required to teach the limitations of claims 6-7.
Regarding claims 8, Schnee teaches that the poly(A) tail comprises a sequence of at least 23 adenosine nucleotides (page 47).
Regarding claims 11-12, Schnee teaches that the coding sequence may encode a fragment of an antigenic peptide or protein (claim 1), wherein the fragment is at least 5 amino acids long (page 11).
Regarding claim 14, Schnee teaches that the RNA can be less than 200 nucleotides long. The 5’-Cap m7GpppN is one nucleotide long; the coding sequence is at minimum 21 nucleotides long (3-nucleotide-long start codon, 15 nucleotides to encode a 5-amino-acid-long peptide fragment, 3-nucleotide-long stop codon); the poly(A) tail is at least 23 nucleotides long (see above, claims 1, 4, 17, and pages 10-11, 15-16, 36, 47). The length of this minimum sequence is 45 nucleotides.
Regarding claim 15, Schnee teaches that the RNA backbone may be chemically modified (pages 14, 49-50).
Regarding claims 17-18, Schnee teaches that the coding sequence encodes a peptide or peptide fragment derived from a viral infectious agent (rabies) (claim 1).
Regarding claim 20, Schnee teaches that cells comprising the RNA express the encoded peptide (page 76).
Regarding claims 22-25, Schnee teaches compositions comprising one or more of the RNA sequences, encompassing compositions wherein the different RNA sequences differ by any means, including length of the 5’-Cap, 5’-UTR, coding sequence, or poly(A) sequence, each of which Schnee teaches can be of a wide range of different lengths and sequences (claim 24, teaching the composition; claims 1, 4, 17; pages 10-11, 15-16, 36, 47, teaching different lengths and sequences of the different components).
Regarding claim 26, Schnee teaches a pharmaceutical composition comprising the RNA (claim 25).
Regarding claim 27, Schnee teaches that the RNA may be used for diagnostic methods (pages 76-77), and teaches kits comprising the RNA (claim 28).
Regarding claim 28, Schnee teaches that the coding sequence encodes a peptide of an infectious agent (claim 1).
Regarding claims 30-31 and 39, Schnee teaches that the RNA can be used as a medicament (claims 29-30) or a vaccine (page 1), for use in the treatment or prevention of an infectious disease (claims 29-30).
However, Schnee does not teach that the RNA is modified enzymatically or that the RNA is single-stranded, or that the poly(A) tail is 5 to 10 nucleotides long. Furthermore, Schnee does not teach that the RNA may encode a cancer-associated peptide, for use in a treatment of cancer.
Schlake teaches that a similar RNA molecule can be modified enzymatically, can be single-stranded, and can comprise a short poly(A) tail, and further may encode a cancer-associated peptide for use in a treatment of cancer.
Regarding claim 1, Schlake teaches a chemically-synthesized RNA (an artificial nucleic acid molecule) comprising from 5’ to 3’: a 5’-Cap, a 5’UTR element, a coding sequence, a 3’UTR element, and a poly(A) tail (claims 1, 10, 19, 30). Schlake also teaches that the coding sequence comprises a start codon at the 5’ end and a stop codon at the 3’ end (pages 4, 10, 18, 34). Thus, Schlake teaches an RNA of claimed formula (1), wherein W is a 5’-Cap, X is a 5’UTR sequence, Y is a start codon, and Z is a stop codon linked via a 3’UTR sequence to a poly(A) tail.
Regarding claims 9-10, Schlake teaches that a poly(A) tail may be as short as 10 adenosine nucleotides long (page 105).
Regarding claim 16, Schlake teaches that the RNA is modified enzymatically (page 105, the polyadenylation signal is added enzymatically, the RNA can be methylated by 2’-O-Methyltransferase).
Regarding claim 17, Schlake teaches that the RNA coding sequence encodes a tumor antigen, pathogenic antigen, autoantigen, alloantigen, or allergenic antigen peptide (page 56).
Regarding claim 18, Schlake teaches that the “term ‘pathogenic antigen’ refers to antigenic (poly-)peptides or proteins derived from or associated with pathogens, i.e. viruses, microorganisms, or other substances causing infection and typically disease, including, besides viruses, bacteria, protozoa or fungi” (page 57).
Regarding claim 19, Schlake teaches that the tumor antigen peptide comprises a tumor-specific mutation (page 56).
Regarding claim 21, Schlake teaches that the RNA is single-stranded (page 90).
Regarding claims 36-38, Schlake teaches that the RNA can be used in the treatment of cancer (claim 47), wherein a patient in need thereof is administered the vaccine comprising the RNA (claim 48).
Regarding claim 39, Schlake teaches that the RNA can be used in the treatment or prevention of infectious diseases (claim 47).
Schnee teaches that the RNA is polyadenylated, and can be methylated (page 50), but does not teach that these modifications are performed enzymatically. However, As Schlake teaches that similar RNA molecules can be so modified enzymatically, it would have been obvious to an artisan at the time of filing that the modifications described by Schnee (polyadenylation, methylation) could be performed enzymatically. Moreover, as Schlake teaches that RNA molecules similar to those of Schnee may be stable with poly(A) sequences as short as 10 adenosine nucleotides long, it would have been obvious to an artisan at the time of filing that the RNA molecules of Schnee could comprise shorter poly(A) sequences than those described by Schnee, including poly(A) sequences as short as 10 adenosine nucleotides long. Furthermore, as Schlake teaches that such similar RNA molecules may be single- or double-stranded, it would have been obvious to an artisan at the time of filing that the RNA molecules of Schnee, with similar structure and used for similar purposes, may be either double- or single-stranded.
The general formulae and structures of the RNA molecules of Schnee and Schlake are similar, as shown above (both comprise a 5’-Cap, a 5’-UTR, a coding sequence, and a poly(A) sequence, used in similar methods and applications of treating or preventing diseases, wherein the coding sequence is selected from coding sequences pathologically associated with the disease to be treated or prevented). As Schlake teaches that such an RNA may be used to express a cancer peptide, or fragment thereof, for use in the treatment of a cancer associated with the cancer peptide, it would have been obvious to an artisan at the time of filing that the RNA of Schnee could be modified, by modifying the coding sequence, in order to use the RNA in the treatment of a cancer, as in Schlake.
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.
US 11369691 B2:
Claims 1-2, 15, 20, 22, 26, 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 17 of U.S. Patent No. 11369691 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
~691 recites a synthetic RNA (claim 1), comprising a 5’-Cap (claim 6) and a 3’-terminal poly(A) tail (claim 7), a 5’ and/or 3’ UTR (claim 5), and a coding sequence encoding a therapeutic protein (claim 1). ~691 only teaches coding sequences comprising a start codon and a stop codon (col. 18 lines 15-16). ~691 describes the 5’-Cap structure as “a modified guanosine nucleotide”, encompassing m7Gppp (col. 8 lines 4-9). ~691 also recites that the RNA is chemically modified (claim 2).
US 10568972 B2:
Claims 1-2, 15, 17-18, 20, 22, 26, 30-31, 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-10 of U.S. Patent No. 10568972 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
~972 recites a synthetic RNA (claim 1), comprising a 5’-Cap and a 3’-terminal poly(A) tail (claim 7), a 5’ and/or 3’ UTR (claim 6), and a coding sequence encoding a viral protein (claim 1). ~972 only teaches coding sequences comprising a start codon and a stop codon (col. 17 lines 48-50). ~972 describes the 5’-Cap structure as “a modified guanosine nucleotide”, encompassing m7Gppp (col. 7 lines 50-55). ~972 also recites that the RNA is chemically modified (claims 8-10). ~972 recites that the RNA encodes an infectious viral agent (claim 1), and is for use as a medicament in the treatment or prevention of an infectious disease (claim 1).
Conclusion
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636