DETAILED ACTION Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The application is a national stage entry of 35 U.S.C 371 of PCT/EP2022/067290 (filed on 06/23/2022) and claims foreign priority to EUROPEAN PATENT OFFICE (EPO) 21181596.4 (filed on 06/24/2021).
Claims Status
The claims 1 and 3-21 are pending and have been considered on the merits.
Drawings
The drawings filed on 12/22/2023 are objected to because they contain color images, but there is no granted petition for color 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).
Claim Interpretation
For clarity of the record the following comments are made regarding claim interpretation under broadest reasonable interpretation:
Regarding claims 4 and 19, the claims recite a product-by-process limitation. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process (See, MPEP 2113).
In the instant case, claim 4 is directed to an oligonucleotide molecule of claim 1. The oligonucleotide molecule is required to have 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein at least 60% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues, and has the functional properties required by claim 1. The claim states the oligonucleotide molecule is synthesized from deoxynucleotides. Physically, he resulting oligonucleotide molecule would have 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein at least 60% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues; thus the synthesization from deoxynucleotides still results in an oligonucleotide as described above and in claim 1. Therefore, any oligonucleotide having 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein at least 60% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues and otherwise meet the functional limitations of claim 1, would read on this limitation.
For claim 19, the claim is directed to an oligonucleotide of claim 1 (described above) wherein: >70% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues, and the oligonucleotide molecule is synthesized from deoxynucleotides, and has the functional properties required by claim 1. The resulting oligonucleotide molecule would have 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein > 70% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues; thus the synthesization from deoxynucleotides still results in an oligonucleotide as described above and in claim 19.Therefore, any oligonucleotide having 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein >70% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues and otherwise meet the functional limitations of claim 1, would read on this limitation.
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, 3-8 and 10-12, and 16-21 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 claims 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.
The claims under rejection are drawn to an oligonucleotide molecule having 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein at least 60% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues (structural limitation). The oligonucleotide molecule is further characterized by functional limitation of its ability to inhibit tumor growth, and/or inhibit replication of monkeypox, and/or inhibit viral or bacterial replication, and/or exert anti-inflammatory effects in mammalian cells (functional limitation). The oligonucleotide molecule, initially characterized in claim 1, covers a genus of molecules: any oligonucleotide molecule comprising at least one G-quartet forming motif would satisfy the structural and functional limitations required by the claim.
Regarding the structural limitation of the oligonucleotide molecule, Chambers et al identified 716,310 distinct G-quadruplexes (G4) within DNA or RNA sequences that are can be targeted for cancer intervention (See, Abstract; Chambers et al (Nature biotechnology, 2015)). When the functional limitation of the claim is included, it is unclear which molecules satisfy the limitation of the molecules’ ability to inhibit tumor growth, and/or inhibit replication of monkeypox, and/or inhibit viral or bacterial replication, and/or exert anti-inflammatory effects in mammalian cells; especially the combination thereof.
Therefore, the issue at hand is the specification fails to provide sufficient information to show Applicants were in possession of the full scope of the genus of oligonucleotide sequences / molecules that would satisfy both the structural and the functional properties of the claim. To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus of molecules, it must be clear that: (1) the identifying characteristics of the claimed molecules have been disclosed e.g. 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; or (2) a representative number of species within the genus must be disclosed. 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, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112 (a), para. 1.
In the instant case, Applicants disclosed SEQ ID NO: 1-4, sequences that the oligonucleotide of the invention can comprise (See, SPEC ¶0020) and 7 were exemplified in example 1 but only 2 of the ODNs in example 1 would satisfy the structural and functional limitations of claim 1 (See, SPEC ¶0057). Therefore, Applicants disclosed 2 species of oligonucleotides that having 10 to 50 nucleotides that form at least on G-quartet forming motif comprising 10-20 nucleotide residues, wherein at least 60% of the residues of said G-quartet forming motif are guanosine or deoxyguanosine residues; SEQ ID NO: 1 and 3 inhibits SARS-CoV-2 infections (inhibits replication). These two species is not considered representative of the broad breadth of claims as written.
Furthermore, Applicants have not provided any description of core features or structure of the oligonucleotide that couple with the function of being able to inhibit tumor growth, and inhibit replication of monkeypox, and inhibit viral or bacterial replication, and exert anti-inflammatory effects in mammalian cells. Applicants have not identified which sequences or SEQ ID NO: 1-4 have the functional capacity to inhibit tumor growth, and/or inhibit replication of monkeypox, and/or inhibit viral or bacterial replication, and/or exert anti-inflammatory effects in mammalian cells; thus one having ordinary skill in the art would be unable to determine what alternative sequences would also be to inhibit tumor growth, and/or inhibit replication of monkeypox, and/or inhibit viral or bacterial replication, and/or exert anti-inflammatory effects in mammalian cells.
Based on the lack of disclosure of a representative number of species, combined with the lack of disclosure of identifying characteristics (e.g. disclosure of functional characteristics coupled to structural features/core structure) the application is determined to fail to provide written description of the genus of oligonucleotide molecules covered by claim 1.
Regarding claims 3-8 and 10-12, and 16-21, these claims are dependent on claim 1 or are drawn to a method of using the oligonucleotide of claim 1, therefore these claims are included in the rejection due to their dependency.
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.
Claims 1, 3-4, 8-13, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kmiec et al (US2008/0096838 A1).
Kmiec et al discloses a guanosine-rich polynucleotide molecule with therapeutic utility of treating or preventing growth of cancerous cells (See, Abstract).
Regarding claim 1, Kmiec et al discloses a guanosine-rich oligonucleotide (GRO), that form G-quartets, that inhibits cell cycle progression and viability of cancer cells (¶0004-0007). This reads on, an oligonucleotide molecule…that form at least one G-quartet forming motif. The invention comprises polynucleotide of approximately 19-21 guanosine residues in length. This reads on, an oligonucleotide molecule having 10-50 nucleotides. Kmiec et al discloses synthetic DNA molecules described as GRO in the invention has sequence of SEQ ID NO:1 (See, ¶0045), which consists of 20 guanosine residues, that forms a G-quartet structure which promotes apoptosis in cells and inhibits cell growth in cancer cells (See, ¶0038-0039). This reads on,…wherein: at least 60% of the residues of said G-quartet forming motif are guanosine, as 100% of the G-quartet forming motif are guanosine. Kmiec et al disclose in example 8, that the mice with cancerous tumors were dosed with oligonucleotide of SEQ ID NO:1 for one week and there was a decrease in the tumor volume and increase in animal viability (See, ¶0129-0132). This reads on, the oligonucleotide molecule inhibits tumor growth… in mammalian cells.
Regarding claim 3, following the discussion above, the oligonucleotide disclosed by Kmiec et al reads on wherein >70% of the residues are guanosine residues, as it is 100% guanosine residues.
Regarding claims 4 and 19, following the discussion above, these claims are product by process claims and Kmiec et al disclosed an oligonucleotide with >70% of the residues are guanosine resides.
Regarding claim 8, following the discussion above, the oligonucleotide disclosed by Kmiec et al reads on wherein 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine residues, as it is 100% guanosine residues and is 20 bases long, there are 6 consecutive triplets.
Regarding claim 9, following the discussion above, the oligonucleotide disclosed by Kmiec et al has SEQ ID NO: 1, which is identical to SEQ ID NO:1 of the instant application (See, Sequence alignment at the end of the action). This reads on, wherein in 10 to 50 nucleotides of the oligonucleotide molecule comprise…SEQ ID NO: 1.
Regarding claim 10, following the discussion above, Kmiec et al disclosed the pharmaceutical composition comprising the GRO with SEQ ID NO: 1, further comprises a PEG buffer or other suitable solutions for injections into a cancer tumor or into a patient’s bloodstream (See, ¶0040). This reads on, a pharmaceutical composition comprising: at least one oligonucleotide molecule according to claim 1, and at least one of pharmaceutically acceptable excipient, carrier, adjuvant, or combination thereof, as PEG buffer is an acceptable carrier.
Regarding claim 11, following the discussion above, Kmiec et al discloses a kit utilizing the methods and components of the invention (See, ¶0105). This includes the GRO of SEQ ID NO:1. This reads on, a kit comprising at least one oligonucleotide molecule according to claim 1.
Regarding claim 18, following the discussion above, Kmiec et al disclosed in example 8 the oligonucleotide was administered by intravenous (IV) at day 1 and 3 of 1 week (See, ¶0129-0132). This reads on, wherein the oligonucleotide molecule is administered in a pharmaceutically acceptable route selected from the group… parenterally.
Regarding claim 20, following the discussion above, Kmiec et al disclosed an oligonucleotide with 100% guanosine residues and with 6 consecutive triplets of guanosine residues. This reads on, wherein >70% of the residues are guanosines…and the 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine residues.
Regarding claims 12 and 13, following the discussion above, Kmiec et al disclosed in example 8, that the mice with tumors were dosed with oligonucleotide of SEQ ID NO:1 for one week and there was a decrease in the tumor volume and increase in animal viability (See, ¶0129-0132 and Figures 11-14). This reads on, a method of precenting or treating a tumor,… in a patient in need thereof comprising administering a therapeutically effective amount of at least one oligonucleotide molecule according to claim 1 to the patient, of claim 12. This also reads on, wherein the oligonucleotide molecule induces inhibition of tumor growth in a mammalian cell of claim 13.
Therefore, claims 1, 3-4, 8-13, and 18-20 are anticipated by Kmiec et al.
Claims 1,3-6, 8, and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hanecak et al (US2007/0015723 A1; as cited in IDS filed on 3/20/2026).
Hanecak et al disclosed a modified oligonucleotide with conserved G4 sequence with flanking nucleotides that can inhibit the activity of virus or telomere length of a chromosome, such that there is an effect in malignant cell growth (See, Abstract).
Regarding claim 1,3,8, and 20, Hanecak et al disclosed oligonucleotides with guanosine nucleotides can form arrays known as G-quartets and they are able to inhibit viral gene expression, viral growth, and inhibits PLA2 enzyme activity (See, ¶0023-0024). Hanecak et al disclosed various oligonucleotides with phosphorothioate deoxyoligonucleotides, including ISIS # 4560 / SEQ ID NO: 42 (See, p 10, Table 4). This sequence has at least four consecutive triplets of guanosine or deoxy-guanosine residues with 84% of residues of the G quartet forming motifs are guanosine residues and inhibit 100% of enzymatic activity against Herpes simplex virus (HSV) (See, p 10 Table 4). This reads on, an oligonucleotide molecule having 10-50 nucleotides that form at least one G-quartet forming motif comprising 10-20 nucleotides residues, wherein: at least 60% of residues of said G-quartet forming motif are guanosine resides…, and the oligonucleotide molecule inhibits viral replication of claim 1. This reads on, wherein >70% of the residues are guanosine residues of claim 3. This reads on, wherein the 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine residues of claim 8. This reads on, wherein >70% of the residues are guanosine residues, and 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine residues of claim 20.
Regarding claim 4, following the discussion above, Hanecak et al disclosed oligonucleotides with phosphorothioate deoxyoligonucleotides, including SEQ ID NO: 42. Hanecak et al disclosed that SEQ ID NO 42 (ISIS # 4560) is a phosphonothioate deoxyoligonucleotides (See, p10 Table 4); that were synthesized with 3’ based bound to the CPG to start synthesis was 2’ deoxynucleotide (See, ¶0077-0078). This reads on, wherein the oligonucleotide molecule is synthesized from deoxynucleotides.
Regarding claims 5 and 6, following the discussion above, Hanecak et al disclosed that the preferred embodiments of the invention are oligonucleotides with modified intersugar linkages (backbones) to be phosphorothioates or phosphotriesters. Further that a fluoresceine moiety makes be added to the 5’ end of the oligonucleotide (See, ¶0054). Hanecak et al disclosed oligonucleotides with phosphorothioate deoxyoligonucleotides, including SEQ ID NO: 42. Hanecak et al disclosed that SEQ ID NO 42 (ISIS # 4560) is a phosphonothioate deoxyoligonucleotides (See, p10 Table 4); This reads on, wherein at least one of the guanosine residues is chemically modified of claim 5. This also reads on, wherein the chemical modification is phosphate backbone modification of claim 6.
Regarding claim 19, following the discussion above, Hanecak et al disclosed that has 84% guanosine residues and the oligonucleotide molecule is synthesized from deoxynucleotides. This reads on, wherein >70% of the residues are guanosine residues, and the oligonucleotide molecule is synthesized from deoxynucleotides.
Therefore, claims 1,3-6, 8, 19, and 20 are anticipated by Hanecak et al.
Claims 1, 12, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jing et al (Cancer research, 2004) and evidenced by Hodge et al (European journal of cancer, 2005).
Jing et al teaches G-rich oligodeoxynucleotides, which form intramolecular G-quartet structures (GQ-ODN) as a new Stat3 inhibitor; that when delivered into tumor xenografts induces tumor cell apoptosis (See, Abstract).
Regarding claim 1, Jing et al teaches in table 1, sequences of the compounds of GQ-ODN, with T40214 and T20231 were used in the assays of by Jing et al (See, p6605 table 1). T40214 is 16 bases long, has 4 consecutive triplets of guanosine residues, and 75% of the residues are guanosine (See, Tabel 1). This reads on, an oligonucleotide molecule having 10-50 nucleotides that form at least one G-quartet forming motif comprising 10-20 nucleotides residues, wherein: at least 60% of residues of said G-quartet forming motif are guanosine resides…of claim 1.
Jing et al teaches that the GQ-ODN T40214 was labeled with fluorescein and injected with polyethyleneimine into the tail veins of nude mice with tumor xenografts (See, p6606 col 1 paragraph 1). Figure 5 shows that the tumors had fluorescent staining, indicating the GQ-ODN entered and accumulated in the tumor cells (See, p6606 col 1 paragraph 1 and Figure 5). Figure 5 also shows that the tumor size of mice with tumors that received the GQ-ODN T40214 or T40231 had an inhibition of tumor growth compared to control (See, p6606 col 1 paragraph 2 and Figure 5). This reads on, the oligonucleotide molecule inhibits tumor growth…in mammalian cells.
Regarding claim 12, following the discussion above, Jing et al teaches the administration of the oligonucleotide molecule as described in claim 1 into a patient (mice) with tumors at 2.5 mg/kg (See, p6606 col 1 paragraph 1). This reads on, a method of precenting or treating a tumor,… in a patient in need thereof comprising administering a therapeutically effective amount of at least one oligonucleotide molecule according to claim 1 to the patient.
Regarding claim 16, following the discussion above, Jing et al teaches the mice with tumors that were treated with GQ-ODN T40214 has a decrease in tumor growth and a decrease in Stat3 (See, p6606 col 2 paragraph 1 and Figure 6). Stat3 is a member of an interleukin signaling pathway through IL6 and JAK, as IL6 directly activates STAT3 through JAK, evidenced by Hodge et al (See, p2503 col 2 paragraph 2 and Figure 2). Therefore, this reads on, wherein the treatment of the… tumor growth results…from suppression with interleukin mediated signaling.
Therefore, claims 1, 12, and 16 are anticipated by Jing et al and evidenced by Hodge et al (European journal of cancer, 2005).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 7 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Hanecak et al (US2007/0015723 A1; as cited in IDS filed on 3/20/2026) as applied to claims 1,3-6, 8, 19, and 20 above.
The teachings of Hanecak et al are forth above.
Regarding claims 7 and 21, Hanecak et al discloses that the oligonucleotides of the invention comprise from 6 to 27 nucleic acid bases with the essential feature of conserved GGGG core sequence flanked by additional bases to inhibit activity (See, ¶0056-0089). Hanecak et al disclosed that the preferred embodiments of the invention are oligonucleotides with modified intersugar linkages (backbones) to be phosphorothioates or phosphotriesters. Further that a fluoresceine moiety may be added to the 5’ end of the oligonucleotide (See, ¶0054). Hanecak et al disclosed various oligonucleotides with phosphorothioate deoxyoligonucleotides SEQ ID NO: 42 (See, Table 4). Therefore, Hanecak et al disclosed an oligonucleotide that has been chemically modified such that has phosphorothioate backbone.
While Hanecak et al is silent on the percentage of the sugar-phosphate backbone that is substituted, it is considered to be prima facie obvious. Given that the substitution of the backbone is modified chemically, determining the optimum percentage of substitution of the sugar-phosphate backbone with phosphorothioate such that the oligonucleotide molecule is therapeutically effective as in Hanecak et al with at least 35% substitution, would have been a matter of routine optimization (See, MPEP 2144.05).
Therefore, claims 7 and 21 are rendered obvious by Hanecak et al.
Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hanecak et al (US2007/0015723 A1; as cited in IDS filed on 3/20/2026) as applied to claims 1,3-6, 8, 19, and 20 above, and further in view of Lai et al (Molecular therapy: the journal of the American Society of Gene Therapy, 2008).
The teachings of Hanecak et al are set forth above.
Regarding claims 12-15, Hanecak et al discloses in example 11, G4 Phosphorothioate oligonucleotides against several viruses including HIV and HSV-2 in MA104 cells, Respiratory syncytial virus (RSV) in Hep-2 cells, and influenza in MDCK cells (See, ¶0092).
Hanecak et al seeded the cells into 95 well culture plates and grown to monolayer. The compound with oligonucleotides and diluted virus were added to the cells (See, ¶0096-0097). Hanecak et al disclosed that in Table 7 oligonucleotides with ED50 values less than 50 μM are considered active and preferred. Compound 5652 (SEQ ID NO: 37), that is 20 nucleotides and 60% of them are guanosine, has 1.9 in ED50 for RSV and 0.6 in ED50 for Influenza (See, p15 Table 7, ¶0098), indicating that this oligonucleotide would be preferred for preventing or treating viral infection.
This reads on, wherein the oligonucleotide molecule induces inhibition of viral replication in mammalian cell of claim 13.
This reads on, wherein the viral infection is caused by virus selected from the group…. RSV virus, influenza virus, HIV virus...of claim 14.
This reads on, wherein the method of treats or prevents a viral infection of the respiratory tract of claim 15, as RSV and influenza are viral infections of the respiratory tract.
Hanecak is silent on administrating this dosage to a patient or subject and only showed efficacy on cell lines.
Lai et al teaches the use of phosphorodiamidate morpholino oligomers (PPMO) AUG-2 as an anti-RSV therapeutic. Lai et al tested AUG-2 PPMO in cell culture showed minimal cytotoxicity and reduced viral titers and when given intranasally to mice prior to RSV inoculation, there was a reduction in viral titers post infection and attenuated inflammation post infection (See, Abstract).
Given that Hanecak et al teaches using oligonucleotide molecule as characterized in claim1 to prevent or treat RSV or influenza in cells, it is implicit to treat diseases and viruses in subjects or patients. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to apply the compound that was tested on cells in Hanecak et al to a subject or patient. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to modify the method of Hanecak et al to administer the compound of the oligonucleotide molecule to mouse/patient to prevent or treat RSV. One would have been motivated to make this modification, due to the success of Lai et al and the normal progression of testing compounds on cells and then to subjects/patients. One would have had a reasonable expectation of success evidenced by Lai et al.
Therefore, claims 12-15 are rendered obvious by Hanecak et al in view of Lai et al.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Kmiec et al (US2008/0096838 A1) as applied to claims 1, 3-4, 8-13, and 18- 20 above.
The teachings of Kmiec et al are set forth above.
Regarding claim 17, following the discussion above, Kmiec et al disclosed a method of administering to a patient in need thereof, an oligonucleotide with 10 to nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine residues.
Kmiec et al discloses that the nucleic acid molecule of the invention can be modified to enhance its stability by chemically modifying the oligonucleotide inter-nucleotide linkages with phosphorothioate. Kmiec et al further discloses that the chemical modification can maintain or enhance activity of the nucleic acid molecule of the invention, due to its resistance to nucleases; thus, making it an effective intracellular therapeutic agent (See, ¶0053-0054). Kmiec et al discloses phosphorothioate oligodeoxynucleotides are relatively nuclease resistant and still hybridize with their RNA targets (See, ¶0063).
Kmiec et al does not teach an oligonucleotide chemically modified to have a phosphate backbone, one would have been motivated to modify the oligonucleotide GRO of Kmiec et al to be chemically modified to have phosphate backbone. It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kmiec et al to have the GRO with phosphate backbone. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification of the GRO based on the teachings and disclosure of Kmiec et al. One would have had a reasonable expectation of success evidenced by Kmiec et al.
Therefore, claim 17 is rendered obvious by Kmiec et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
APPENDIX
Sequence Alignments:
RE: Kmiec et al US 2008/0096838A1
Query (instant SEQ ID NO: 1) vs Subject (referenced SEQ ID NO: 1)
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