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 .
Status of Claims
The amended claims filed 06/02/2026 are acknowledged and entered.
Claims 3, 5, 11-12, 22, 27 have been amended.
Claims 1-2, 4, 6-10 and 28 are cancelled.
Claims 30-32 are new
Claims 15-21 and 23-27 are withdrawn.
Claims 3, 5, 11-14, 22, 29-32 are pending and examined on their merits.
Response to Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Objections
Nucleotide and/or Amino Acid Sequence Disclosures – Withdrawn
Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Specification - Withdrawn
The disclosure was objected to because of the following informalities:
The use of the term(s), which are a trade name or a mark used in commerce,
The use of hyperlinks.
Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
1. The rejections for claims 1-2 and 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of claims 1-2 and 4, being cancelled.
2. The rejections for claim 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of claim 3, being amended
3. The rejections for claims 1, 2, 6, 10, 12, 14, and 28 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.is withdrawn in view of claim 1-2, 6, 10 and 28 being cancelled and 12 and 14, being amended.
Claim Rejections - 35 USC § 101 - Withdrawn
4. The rejection of claims 1-7, 10, 22, and 28 are rejected under 35 U.S.C. § 101 because the claims recite nature-based products that are not markedly different from the products as they are found in nature is withdrawn in view of claims 1-2, 6 and 10 being canceled and independent claim 3 being amended to incorporate delivery vehicles that are not found in nature.
Claim Rejections - 35 USC § 102 - Withdrawn
5. The rejections of claims 1-3, 12, 13, and 28 under 35 U.S.C. § 102(a)(1) as being anticipated by Hofmann (previously cited) are withdrawn in view of claims 1-2, and 28 being canceled and claims 3, 12 and 13 being amended.
Claim Rejections - 35 USC § 103 - Withdrawn
6. The rejections of claims 2 and 6-10 under 35 U.S.C. 103 as being unpatentable over Hofmann in view of Wang (previously cited) are withdrawn in view of the cancellation of claims 2 and 6-10.
Objections/Rejections Maintained
Specification – Maintained
7. Applicant has corrected the informalities in the substitute Abstract as requested but there is now a new typo: The first word “Provides” should be written as Provided”.
Claim Rejections - 35 USC § 103 - Maintained
8. Claims 3, 5, 11-14, 22 and 29 remain rejected under 35 U.S.C. § 103 as being unpatentable over the combined teachings of Hofmann in view of MN908947.3, (previously cited) Crooke (previously cited), Spurgers (previously cited) and Wang (previously cited). Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- Claim 3 is amended to be in independent form, incorporate limitations of claims 4, 6 and 10 and to recite that "nucleotide residues at 5' and 3' ends of the nucleic acid molecule are 2'-O-methoxyethyl modified."
The cited references do not disclose or suggest the presently claimed nucleic acid at least because they do not disclose the sequences recited in the present claims including the 5'-end linker region and the specific nucleic acid modifications.
For at least these reasons, the present claims are patentable over the cited references alone or in combination.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
The amended claim 3 reads as follows (the changes are underlined, bolded and given a letter name for easier identification of the new limitations in the discussion):
3. (Currently Amended) A nucleic acid molecule that binds to a negative-strand ribonucleic acid (RNA) molecule produced by a coronavirus, wherein said nucleic acid molecule comprises:
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; and
a 5'-end linker region that comprises a sequence complementary to a sequence of the negative-strand RNA starting at the 3'-end of the poly(U) stretch,
wherein the 5'-end linker region is located at the 5'-end of the poly(A) stretch, within the poly(A) stretch, or at the 3'-end of the poly(A) stretch, and comprises the nucleotide sequence 5'-GGAGAATGAC-3' (SEQ ID NO: 5), (limitation a)
wherein the 5' terminal nucleotide and the 3' terminal nucleotide of the nucleic acid molecule are each a 2'-O-methoxyethyl modified nucleotide; (limitation b)
wherein said composition further comprises a delivery vehicle selected from the group consisting of a hydrogel, a cyclodextrin, poly(lactic-co-glycolic)acid (PLGA), a microsphere, a nanocapsule, a surface-modified liposome, a polyethylenimine (PEI) polymer, a polyethylenimine derivative, and a linear poly methacrylate cationic polymer. (limitation c)
As discussed in more detail in the previous office action, Hofmann teaches probes and primers that can bind to a negative strand RNA (RNA(-)) produced by a coronavirus, in this case Bovine coronavirus (BCV). In addition, Hofmann 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 (that is between 5 and 50 bases) capable of hybridizing a 5'-poly(U) stretch. These teachings read on a nucleic acid molecule that binds a coronavirus RNA(-), wherein said nucleic acid molecule comprises a poly(A) stretch that is between 5-50 bases in length capable of hybridizing to a 5'- poly(U) stretch in said RNA(-) molecule;
The limitations (a, b and c) incorporated from claims 4, 6 and 10 are also discussed in the previous office action but are summarized here:
MN908947.3 teaches the 5'-end linker region and includes sequences also found in SEQ ID NO: 1 (see previous office action) and SEQ ID NO: 5 (see alignment below), which is the sequence GGAGAATGAC (the first 10 bases of SEQ ID NO: 1) SEQ ID NO; 5 comprises a sequence complementary to a sequence of the RNA(-) starting at the 3'-end of the poly(U) stretch, that is the 5’-end poly(A) stretch in the RNA(+) as shown below (limitation a).
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Limitation b recites: the "nucleotide residues at 5' and 3' ends of the nucleic acid molecule are 2'-O-methoxyethyl modified” and it is taught by Crooke. Paragraphs [0188] Natural and Modified nucleobases, [0189], [0216], [0407], [0450], [0460], example 31, table 16 and claim 39, all discussed 2'-O-methoxyethyl modifications. In addition, it would further be obvious that location(s) of the 2'-O-methoxyethyl modifications in a composition (since the nucleic acid molecule needs binds to the RNA(-), the least intrusive locations for the modifications would be the 5’ and 3’-ends of the molecule), or the optimal length of the poly(A) stretch are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters 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 amount of each ingredient 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.
Limitation c wherein the composition further comprises a delivery vehicle selected from the group consisting of a hydrogel, a cyclodextrin, poly(lactic-co-glycolic)acid (PLGA), a microsphere, a nanocapsule, a surface-modified liposome, a polyethylenimine (PEI) polymer, a polyethylenimine derivative, and a linear poly methacrylate cationic polymer is taught by Wang. As discussed in the previous non final office action (instant claims 6-10 section), Wang teaches polyethyleneimine-based nanocarriers for gene delivery including a wide range of nanocarriers such as nanoparticles, nanocapsules, micellar systems, and nanoconjugates. 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. That is, PEI is a polymer that can be used as a delivery vehicle for a nucleic acid and can form a nanocapsule.
In addition, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The combined teachings of the references relevant to the rejection under 35 U.S.C. 103 and the motivation to combine these references have been discussed in the previous office action and above. Applicant has not sufficiently described why there is no prima facie case for obviousness.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
New Rejections Based on Amendments
Claim Rejections - 35 USC § 112(b)
9. Claims 3, 29-32 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 3 recites the limitation: “….wherein said composition further comprises…” There is insufficient antecedent basis for the term “composition” in the claim.
Claims 29-32 depend on canceled claims (claims 28 and 1) and thus the dependency is unclear as all the limitations these claims may have are not known. For the purposes of compact prosecution claim 29 has been interpreted to depend on claim 3 since claim 3 is the independent claim.
Claim Rejections - 35 USC § 112(d)
Claims 11 and 29 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 11 depends on claim 3, Claim 29 has been interpreted as dependent on claim 3. Claim 3 recites the limitation: “… wherein the 5' terminal nucleotide and the 3' terminal nucleotide of the nucleic acid molecule are each a 2'-O-methoxyethyl modified nucleotide….”, Claims 11 and 29 do not include all the limitations of claim 3 in all embodiments as they include “a modified base, a base analog, and an abasic site”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
10. Claims 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Hofmann in view of MN908947.3, Crooke, Spurgers, Wang and Hadjinicolaou (Arch Virol (2011) 156:671–680).
The teachings of Hofmann, MN908947.3, Crooke, Spurgers and Wang have been discussed in the previous office actions and above and are therefore incorporated herein.
Hofmann, MN908947.3, Crooke, Spurgers and Wang do not teach the use of FRET or molecular beacon probes.
Hadjinicolaou teaches the development of a molecular-beacon-based multi-allelic real-time RT-PCR assay for the detection of human coronavirus causing severe acute respiratory syndrome (SARS-CoV): a general methodology for detecting rapidly mutating viruses (title). Hadjinicolaou uses primers and molecular beacons to detect the SARS-CoV S, E, M and N genes using fluorescence. Figure 1 teaches the assay design. In particular, Figure 1C shows the amplicons of each of the four genes (S, E, M and N) incorporated in the assay. All beacons were labelled with DABCYL, (40-(40-dimethylaminophenylazo) benzoic acid) (that is the quencher) at the 3’ end and TET (tetrachloro-60-carbofluorescein) at the 5’-end (fluorophore) except MBIPC, the IPC beacon, which was labelled with FAM (fluorescein - fluorophore) (page 67, Molecular beacon and primer design section). Fluorophores and quenchers probes are required for molecular beacon and/or FRET (broader detection category than molecular beacons) analysis as required by instant claims 30-32.
It would have been obvious to one of ordinary skill in the art to use the teachings of Hofmann, MN908947.3, Crooke, Spurgers and Wang with Hadjinicolaou and incorporate fluorescence, FRET or molecular beacon detection systems to the nucleic acid that binds the RNA(-) of coronavirus recited in Claim 3. One of ordinary skill would have been motivated to do so because fluorescence, FRET or molecular beacon detection systems have been successfully utilized to detect SARS-CoV, a coronavirus, including those rapidly mutating viruses. There would be a reasonable expectation of success because these detection systems, or variants thereof, are routinely used to detect many sorts of agents in labs all over the world.
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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for replying to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/Michael Allen/ Supervisory Patent Examiner, Art Unit 1671
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