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 .
Preliminary Amendment
The preliminary amendment dated 12/08/2025 has been entered. Claims 1-29 are pending.
Information Disclosure Statement
The submitted Information Disclosure Statement(s) (IDS) submitted on 11/15/2022 and 02/07/2025 have been considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest possible effective filing date for the instant claims is May 15, 2020 based on the filing date of the provisional application 63/025,613
Election/Restriction
Applicant’s election without traverse of Group I in the reply filed on 12/08/2025 is acknowledged.
Claims 15-21 and 23-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-14, 22 and 28-29 are under examination.
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 – 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:
i) the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
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 of the material 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.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in claim 4 (GGAGAATGAC sequence) is not identified by sequence identifiers in accordance with 37 CFR 1.831. Sequence identifiers for nucleotide and/or amino acid sequences must appear in the claims (MPEP 2412.04).
Required response – Applicant must provide:
Replacement claims in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute claims in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the claims, consisting of:
A copy of the previously-submitted claims, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended claims without markings (clean version); and
A statement that the substitute specification contains no new matter.
Objections - Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, For example in page 20 GENBANK (www.ncbi.nlm.nih.gov/genbank/) and EMBL-EBI (www.ebi.ac.uk.).. Applicant is required to delete all 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.
Note that the hyperlinks listed above are merely examples and all improper uses of hyperlinks in the specification should be identified by applicant and properly addressed.
Appropriate correction is required.
The use of the terms TAQMAN, SYBR and EvaGreen, which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that ‘TAQMAN, SYBR and EvaGreen' are merely examples and all improper uses of trademarks in the specification should be identified by applicant and properly addressed.
Appropriate correction is required.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The present disclosure provides”, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Appropiate correction is required.
Claim Rejections - 35 USC § 112
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.
1. Claim 1-4, 15-17, 19-21 and 23 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
Claim 1-2, 15-17, 19-21 and 23 recites “….“preferably SARS CoV-2…”. The phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 3 recites the limitation "….comprises a 5'-end linker region that comprises a sequence complementary to a sequence at the 5'-end of the negative-strand RNA.”. This definition of the linker is unclear, because the orientation of the linker region in relationship with the poly(A) stretch has not been clearly defined. For the purposes of compact prosecution, claim 3 has been interpreted as follows: The linker region can be found at the 5’-end of the poly(A) stretch (SEQ ID NO: 1), at the 3’-end of the poly(A) stretch, or inserted in the middle of the poly(A) stretch (SEQ ID NO: 2). This linker region comprises a sequence that is complementary to the sequence found at the 3’-end of the poly (U) stretch of the negative-strand RNA molecule.
Claim 3 recites the limitation "…. that starts immediately after the poly(U) stretch.”. This limitation is unclear, because it is not known what it is meant by “after” if it is immediately upstream or downstream of the poly(U) stretch, or If it is immediately 5’ or 3’ to the polyU stretch For the purposes of compact prosecution, claim 3 has been interpreted as follows: “….the linker sequence is complementary to a sequence in the negative-strand RNA found at the 3’-end of the poly(U) stretch”.
Claim 4 recites the limitation "…. GGAGAATGAC (nucleotides 1-10 of SEQ ID NO: 1).”. The orientation of the GGAGAATGAC is unclear. For the purposes of compact prosecution, claim 3 has been interpreted as follows: 5’-GGAGAATGAC-3’.
Appropriate correction is required.
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 1-2, 6, 10, 12, 14 and 28 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming.
Claim 1 recites “ an agent selected from the group consisting of a nucleic acid, an antibody, an aptamer, a protein, and a low molecular weight compound” that is capable of binding to a 5'-poly(U) stretch in a coronavirus negative-strand RNA molecule, which encompasses a genus of agents.
Claim 2 recites a nucleic acid molecule that binds to a negative-strand RNA molecule produced by a coronavirus, comprising a poly(A) stretch that is between 5-50 bases in length, capable of hybridizing to a 5'-poly(U) stretch in said negative-strand RNA molecule. Claim 28 depends directly on claim 2 and recites the nucleic acid being DNA, RNA, or DNA and RNA.
Claims 6, 10, 12, 14 and 28 depend directly or indirectly on claim 2 and further comprise a delivery vehicle, and also a heterologous molecule conjugated to the nucleic acid molecule that may target the nucleic acid molecule to a cell or intracellular compartment. Claims 6, 10, 12, 14 and 28 do not materially limit the genus of agents recited by 2, especially regarding the nature of the nucleic acid in claim 2, which is not defined by a SEQ ID NO and so it could be any nucleic acid sequence of any length, comprising 5-50 bases in the poly(A) stretch. The range 5-50 is very broad considering it has to hybridized to a poly(U) stretch of undefined length under unknown conditions and therefore thousands of nucleic acids would fit the limitations of claim 2. Additional limitations in claims 6, 10, 12 and 14 are also very broad as the claims include thousands delivery vehicles and heterologous molecules. For example, any protein is claimed as a potential delivery mechanism or the heterologous molecule can be any molecule. Therefore, these claims are included in the rejection. These claims do not require that the genus of the claims possess any particular clearly defined structure.
Therefore, the claims are drawn to a genus of “agents” as recited in claim 1 or “a nucleic acid molecule with a poly(A) stretch ranging from 5 to 50 bases as recited in claim 2 and dependent claims for which there is inadequate written description.
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 MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a)(i)(C).
In the instant claim 1, the only identifying characteristic present in the claim is a recitation of requisite activity (------------------an agent capable of binding to a 5'-poly(U) stretch in a SARS_CoV-2 negative-strand RNA molecule). There is not even identification of any particular portion of a structure that must be conserved for said activity. Regarding the genus of the claims, the specification describes two specific species within the genus claimed (SEQ ID NO: 1 and SEQ ID NO: 2 [00157]. From the specification, it is clear that Applicant is in possession of species of SEQ ID NOs: 1 and 2. Claim 1, however is not limited to those species but also includes a nucleic acid, an antibody, an aptamer, a protein, and a low molecular weight compound, and the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species, the specification does not provide adequate written description of the claimed genus.
In the instant claim 2 and 28 the only identifying characteristic present in the claim is a recitation of requisite activity (------------------capable of hybridizing to a 5'-poly(U) stretch in a SARS_CoV-2 negative-strand RNA molecule). There is no identification of the sequence, length and type (claim 28) of the nucleic acid and no identification of the minimum number of bases in the poly(A) stretch that are needed for hybridization since the hybridization conditions are not defined. Therefore, there is no clear identification of any particular portion of a structure that must be conserved for said activity. Regarding the genus of the claim 2 and 28, the specification describes two specific species within the genus claimed (SEQ ID NO: 1 with a poly(A) stretch of 25 bases) and SEQ ID NO: 2 (with a poly(A) stretch of 50 bases with a linker inserted in the middle of the poly(A) stretch) [00157]. From the specification, it is clear that Applicant is in possession of species of SEQ ID NOs: 1 and 2. Claim 2 and 28, however, are not limited to those species, as it also includes any nucleic acid sequence of any length and type comprising a range of 5-50 bases, and the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species, the specification does not provide adequate written description of the claimed genus.
In the instant claims 6, 10, 12 and 14 which depend directly or indirectly on claim 2, the only identifying characteristic present in the claim is a recitation of requisite activity (------------------ capable of hybridizing to a 5'-poly(U) stretch in a SARS-CoV-2 negative-strand RNA molecule). In addition to the discussion above for claim 2, there is not a defined identification for the nucleic acid delivery vehicle which can be any protein, or the heterologous molecule that can be conjugated to the nucleic acid molecule. Regarding the genus of the claims, the specification describes two specific species within the genus claimed (SEQ ID NO: 1 with a poly(A) stretch of 25 bases) and SEQ ID NO: 2 (with a poly(A) stretch of 50 bases with a linker inserted in the middle of the poly(A) stretch) [00157]. Three different polymers were tested: (1) branched polyethylenimine ("bPEI," molecular weight ~10kDa); (2) jetOPTIMUS PEI (www.polyplus-transfection.com/products/jetoptimus; "Polymer 1," molecular weight ~10kDa); and (3) linear poly methacrylate cationic polymer ("Polymer 2," molecular weight ~10kDa). From the specification, it is clear that Applicant is in possession of species of SEQ ID NOs: 1 and 2 complexed with the three different polymers. The specification does not show that applicant is in possession of any species of heterologous molecules. Claims 6, 10, 12 and 14, however, are not limited to those species of polymers and claim any heterologous molecule. Therefore, the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species, the specification does not provide adequate written description of the claimed genus.
Claim Rejections - 35 USC § 101
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.
Claims 1-7, 10, 22 and 28 are rejected under 35 U.S.C. 101 because the claims recite “nature-based products” as a limiting element or step without having markedly different characteristics than the nature-based product itself. The claimed inventions are directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application because, the agent that binds the SARS-CoV-2 negative strand RNA molecule is not markedly different from its naturally occurring counterpart in the SARS-CoV-2 positive strand RNA molecule because it conveys the same genetic information and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106 for patent subject matter eligibility analysis.
A claim that focuses on use of a natural product must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural product itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The recent Interim Eligibility Guidance addresses the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions) – Prong 1. “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception. If yes, determine if the claim recite additional elements that integrate the judicial exception into a practical application – Prong 2. If no, proceed to step 2B.
In Step 2B determine whether the claim as a whole amounts to significantly more than the exception.
Claims 1 is drawn to an agent that binds to a negative-strand RNA molecule produced by a coronavirus, preferably SARS-CoV-2, capable of binding to a 5'-poly(U) stretch in said negative-strand RNA molecule, and wherein said agent is selected from the group consisting of a nucleic acid, an antibody, an aptamer, a protein, and a low molecular weight compound
Claim 2 is drawn to a nucleic acid molecule that binds to a negative-strand RNA molecule produced by a coronavirus, preferably SARS-CoV-2, comprising a poly(A) stretch that is between 5-50 bases in length, and wherein said poly(A) stretch is capable of hybridizing to a 5'-poly(U) stretch in said negative-strand RNA molecule.
Claim 3 is drawn to the nucleic acid molecule further comprising a 5'-end linker region that comprises a sequence complementary to a sequence at the 5'-end of the negative-strand RNA that starts immediately after the poly(U) stretch.
Claim 4 is drawn to the nucleic acid molecule wherein the linker sequence comprises GGAGAATGAC (nucleotides 1-10 of SEQ ID NO: 1).
Claim 5 is drawn to the nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2.
Claim 6 is drawn to a composition comprising the nucleic acid molecule, wherein said composition further comprises a delivery vehicle.
Claim 7 is drawn to the composition, wherein the delivery vehicle is a polymer.
Claim 10 is drawn to the composition, wherein the delivery vehicle is selected from the group consisting of a lipid, a liposome, a hydrogels, a cyclodextrin, poly(lactic-co-glycolic)acid (PLGA), a microsphere, a nanocapsule, and a protein.
Claim 22 is drawn to the nucleic acid, wherein the poly(A) stretch is between 20-30 bases in length.
Claim 28 is drawn to the nucleic acid comprising DNA, RNA, or DNA and RNA
The present claims are directed to a composition of matter so Step 1 is satisfied.
Claims 1-5 22 and 28 are directed to a nucleic acid molecule (including RNA) capable of binding to a 5'-poly(U) stretch in SARS-CoV-2 negative-strand RNA molecule. This nucleic acid molecule has to be complementary to the sequence found in the SARS-CoV-2 negative-strand RNA molecule in order to bind it. This nucleic acid molecule includes any fragment of the SARS-CoV-2 positive-strand RNA molecule. Both, the positive and the negative strand RNA molecules are found in nature and do not result in different RNA molecules that exhibits any markedly different characteristics with respect to structure, function, or any other property to distinguish this SARS-CoV-2 positive strand RNA from its naturally occurring counterpart. See Sequence alignment results between SEQ ID NO: 1 (instant claim 5), (including its first 10 nucleotides as required in instant claim 4) and MN908947.3 (GenBank: MN908947.3 Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome. VRL 18-MAR-2020. https://www.ncbi.nlm.nih.gov/nuccore/MN908947). These results established the SEQ ID NO: 1 is identical to this region of SARS-CoV-2 found in nature.
SEQUENCE ALIGMENT
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Claims 6-7 and 10 are directed to the nucleic molecule (including a SARS-CoV-2 positive strand RNA fragment) of claim 2 and a delivery vehicle. The specification defines a “delivery vehicle” as a “lipid, a liposome, a hydrogels, a cyclodextrin…a microsphere, a nanocapsule, and a protein.” ([0016] and [0020]). Therefore, and under the broadest reasonable interpretation (BRI), the nucleic acid of claim 2 could be delivered by a delivery vehicle consisting of the natural virion with its lipid envelope and associated proteins. In addition, under BRI, a “protein” is also considered a “polymer” as well (instant claims 7 and 10).
As such, all of the instant claims recite judicial exceptions in the form of a natural phenomenon (product of nature) (Step 2A, Prong 1- YES).
The core of the instant claims 1-5, 22 and 28 is the nucleic acid molecule capable of binding to a 5'-poly(U) stretch in SARS-CoV-2 negative-strand RNA molecule (which includes a RNA molecule) and the delivery vehicle of instant claims 6-7 and 10 comprises a natural product (the natural virion). The instant claims do not recite any additional elements that integrate this judicial exception into a practical application. Rather, the instant claims merely recite a natural product (a region of the SARS-CoV-2 positive-strand RNA molecule). As such, the instant claims do not recite additional elements that integrate the judicial exception into a practical application (Step 2A, Prong 2- NO).
The claimed RNA, capable of binding to a 5'-poly(U) stretch in SARS-CoV-2 negative-strand RNA molecule, is naturally occurring RNA and the claimed delivery vehicle comprises a natural product, the virion, as demonstrated above and does not reasonably provide an inventive concept or recite any elements beyond the judicial exceptions themselves. As such, the instant claims do not recite any additional elements that amount to significantly more than the judicial exception (Step 2B- NO).
Accordingly, claims 1-7 10, 22 and 28, do not constitute patent eligible subject matter under 35 U.S.C. § 101.
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.
Claims 1-3 ,12-13 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hofmann (J. Virol, Vol. 65, No. 11. Nov. 1991, p. 63316333, IDS 11/15/2022 NPL Cite No 5).
Hofmann teaches probes and primers (that is, agents), including the y-32P-end-labeled oligo(dA)18 probe (page 6332, second column, second paragraph). This probe binds to a RNA (-) produced by a coronavirus, in this case Bovine coronavirus (BCV) (Title) (instant claim 1-3 ,12-13 and 28). In coronaviruses, the poly(U) stretch would be found on the 5' end of the RNA(-), This y-32P-end-labeled oligo(dA)18 probe comprising of adenosines is capable of base pairing to a 5'-poly(U) stretch (Chargaff's rules: adenine (A) always pairs with thymine (T) in DNA and uracil (U) in RNA). In addition, Figure 1 (A) in page 6332 teaches a schematic representation of the 3' end of the BCV genome (and subgenomic mRNAs) shown as plus-strand DNA with a poly(A) tail of 12 nucleotides in length capable of hybridizing a 5'-poly(U) stretch as required in instant claims 2-3 and 28. Figure (A) also teaches the complementary minus strand shown as DNA with a short poly(T) tract [to represent poly(U)] and the sequences and positions of the primers used are also identified in the schematic representation (instant claim 3). The agent is conjugated to a heterologous molecule which is a detectable label (y-32P-end) (instant claims 12-13)
Therefore, the reference teachings anticipate the claimed invention.
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.
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.
Claims 1-5, 11, 12-14, 22 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Hofmann as applied to claims 1-3 ,12-13 and 28 above, and further in view of MN908947.3, Crooke ( US 2005/0100885 Al publication date May 12, 2005, IDS 11/15/2022 US patent applications Cite no 1) and Spurgers (Antiviral Research 78 (2008) 26–36).
Hofmann teachings has been discussed above and applied herein.
MN908947.3 teachings has been discussed above and applied herein. That is, the sequence in MN908947.3, also found in SEQ ID NO: 1, comprises the sequence GGAGAATGAC defined as a linker in instant claims 3-5 and a poly(A) stretch (instant claims 1-5, 22 and 28)
Hofmann and MN908947.3 do not teach the nucleic acid molecule contains a modified base (instant claims 11 and 29) or that the nucleic acid molecule is conjugated to a heterologous molecule targeting the nucleic acid to a cell or intracellular compartment (instant claim 14)
Crooke teaches the design and synthesis of oligomeric compounds and compositions that can be administered to reduce the activity of SARS virus (a Coronavirus), to prevent or treat SARS virus-associated disease, to detect and to diagnose SARS virus-associated diseases (abstract). The compound comprises at least one modified internucleoside linkage, modified sugar moiety, or modified nucleobase [0053]. Such modified or substituted oligonucleotides are often desired over native forms because of desirable properties such as, for example, enhanced cellular uptake [0071] (instants claim 11 and 29).In addition Crooke teaches that these compositions may comprise various penetration enhancers to effect the efficient delivery of nucleic acids, particularly oligonucleotides ([0239] and [0244]). Another modification of the oligonucleotides involves chemically linking to the oligonucleotide one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide [0199] as required by instant claim 14.
Spurgers teaches antisense oligonucleotides (ASO) and siRNA as antiviral therapeutics (Section 4, page 30). Targeting viral RNA sequences with ASOs is a conceptually appealing strategy for treating RNA virus infections for several reasons. First, preventing the synthesis of even one critical viral protein could potentially disrupt the viral life cycle. Secondly, the sequence specificity of ASO potentially allows viral genes to be targeted without affecting host genes, thus decreasing or eliminating unwanted side effects. In addition, targeting viral sequences does not require an understanding of gene function. The feasibility of using ASOs to disrupt RNA virus gene expression was first demonstrated using Rous sarcoma virus in 1978 and many other viruses since (entire article).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Hofmann and MN908947.3 to identify a nucleic acid agent (an RNA and/or DNA oligonucleotide) comprising SEQ ID NO: 1 (using the viral sequence as taught by MN908947.3,) biding a Coronavirus negative-strand RNA molecule comprising the poly(U) tail, and incorporate to this nucleic acid a detectable label such as the y-32P (as taught by Hofmann) and/or modified bases as taught by Crooke. One of ordinary skill would have been motivated to do so because Hofmann, MN908947.3 and Crooke are all related to Coronaviruses and using nucleic acids as antisense oligonucleotides is a well know therapeutic approach in antiviral development as taught by Spurgers. It would have further been obvious to incorporate an heterologous molecule to the nucleic acid to target this nucleic acid agent to the cell or to an intracellular compartment as taught by Crooke. One of ordinary skill would have been motivated to do so because Coronaviruses replicate in the cytoplasm of the cell and thus the oligonucleotide has to be in the cytoplasm in order to bind the negative-strand RNA and exercise its therapeutic effect. It would have further been obvious to test nucleic acid agents of different poly(A) lengths and/or different insertion points for the linker in the poly(A) stretch (such as SEQ ID NO: 2) that a person of ordinary skill in the art would routinely optimize to improve the therapeutic effect. Optimization of parameters such as different poly(A) lengths and/or different insertion points for the linker is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal nucleic acid sequence needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 2. There would be a reasonable expectation of success because Spurgers confirms the feasibility of using oligonucleotides to disrupt RNA virus gene expression and/or replication as first demonstrated using Rous sarcoma virus in 1978 and many other viruses since.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 2 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hofmann, as applied to claim 2 above, and further in view of MN908947.3, Wang (Current Pharmaceutical Design, 2015, 21, 6140-6156)
Hoffman teachings has been discussed above and applied herein.
MN908947.3 teachings has been discussed above and applied herein.
Hofmann and MN908947.3 do not teach the use of a delivery vehicle (claims 6-10).
Wang teaches polyethyleneimine-based nanocarriers for gene delivery (Title) including a wide range of nanocarriers such as nanoparticles, nanocapsules (instant claim 10), micellar systems, and nanoconjugates (Introduction page 6140). Branched polyethylenimine (PEI) is a cationic polymer that contains primary, secondary and tertiary amino groups. This type of polycation with a high density of amines is regarded as one of the most promising cationic vectors for gene delivery. The high density of amino groups can effectively condense nucleic acids into nano-sized particles through a strong electrostatic interaction (Section 2 page 6140) That is, PEI is a polymer that can be used as a delivery vehicle for a nucleic acid and can form a nanocapsule (instant claims 6-10).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Hofmann and GenBank: MN908947.1 to identify a nucleic acid agent (an RNA and/or DNA oligonucleotide) as described above with Wang to develop a delivery mechanism comprising branched polyethyleneimine-based nanocapsules. One of ordinary skill would have been motivated to do so because any agent needs to be delivered (without being degraded) to the location where it is needed for the treatment to be enabled.
There would be a reasonable expectation of success because branched PEI is regarded as one of the most promising cationic vectors for gene delivery as taught by Wang.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/RACHEL B GILL/Primary Examiner, Art Unit 1671