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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/26/2023 has been considered by the examiner.
Specification
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. The following paragraphs of the instant published application, USPgPub 2024/0165217, improperly incorporate subject matter into the instant disclosure:
[0041]: “(Coleman 2008, Nouën 2017, incorporated herein by reference as though fully set forth)”;
[0072]: International Patent Application No. PCT/US2014/015274 (published as WO 2014/124238) herein incorporated by reference as though fully set forth…International Patent Application No. PCT/US2017/053047 (published as WO 2018/057950) herein incorporated by reference as though fully set forth, for example, RSV Min_L-NPM2-1[N88K]L of WO 2018/057950
Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
The use of the term “Codagenix”, which is a trade name or a mark used in commerce, has been noted in paragraph [0191] of the instant published disclosure. 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.
Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered. Applicant' s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
Claims 1-5, 7, 11-17, 22, 27, 33, 34, and 38-42 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.
In claim 1, line 3, it states that the composition comprises a “deoptimized respiratory syncytial virus”, implying a nonspecific, functionally suboptimal virus, without a corresponding attributable structure. Paragraph [0036] of the instant published disclosure, USPgPub 2024/0165217, describes reducing codon pair bias and deoptimized codons. It is presumed that codon deoptimization is the intended genomic manipulation of the respiratory syncytial virus (RSV) claimed since it is the only type of manipulation discussed in the instant disclosure. In the interest of compact prosecution, the claims are interpreted as a codon deoptimized RSV. However, this courtesy does not preempt the requirement for a clarifying amendment. This rejection affects all dependent claims.
Instant claim 1 recites that the effective amount of RSV administered is “about” 103-109 focus forming units (FFU). Claim 7 recites that the amount is “about” 105, “about” 2 x 105, “about” 106, or “about” 2 x 106. Claim 7 does not provide a unit of measurement, i.e., “FFU”, and the quantities intended are indeterminable. Claims 22, 27, and 40-42 also recite effective amounts of RSV administered is “about” 105 or “about” 106 to “about” 2x105 or “about” 2x106 FFU. However, there is no guidance provided in the instant specification or the prior art indicating what quantity range of RSV would result in the asserted “effective amount” required. There is also no guidance provided for what is intended by “about” 28 days or “about” 28-35 days, recited in instant claims 2-4, and 40-42; “about” 1 mL, recited in instant claim 11; “about” four aliquots, recited in instant claim 12; or “about” 5-20 or 10-15 minutes recited in claims 13 and 14, respectively.
Claim Rejections - 35 USC § 103
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 1-5, 7, 11, 15-17, 22, 27, 33, 34, and 38-42 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller et al. (Vaccine. 24 February 2020; 38: 2943-2948), Moore et al. (USPgPub 2016/0030549, hereinafter, “Moore ‘549”), Baer et al. (Journal of Visualized Experiments. 2014; 93: e52065), Rostad et al. (Journal of Virology. 2016; 90 (16): 7508-7518), and SEQ ID NO: 1 alignment with Published_Applications_NA_Main database 16-335-099-14 from USPgPub 20190233476 of LeNouen et al., Mar 2019.
Mueller discloses a method of eliciting a cellular immune response in a subject by administering RSV-MinL4.0, a codon pair deoptimized attenuated vaccine, see the last two paragraphs above “2. Methods” and section 2.2. African Green Monkeys are intranasally and intratracheally administered 2x106 PFU on days 0 and 28 of RSV-MinL4.0, see Group 2 described in section 2.3, as required by instant claims 2-4, 7, and 22. Since there is no requisite quantity of codon deoptimized RSV attributable to an effective amount “about” 103-109 FFU, as recited in instant claim 1, it is determined that 2x106 PFU administered by Mueller et al., is equivalent to “about” 103-109 FFU required in claim 1 and equivalent to “about” 2x105 FFU required in claims 41 and 42. Mueller et al. teach a cellular immune response is induced, as required by instant claims 1, 40. Mueller et al. measure IFNγ cellular immunity by ELISPOT analysis of peripheral blood mononuclear cells (PBMCs) from the subject, see section 2.3, the paragraph above section 3.3, and Figure 3, which shows at least a 1.3 fold increase of spot forming units (SFU) between baseline (Day 0) and post vaccination, as required by instant claims 15-17 and 40-42.
Mueller er al. do not teach that the effective amount of RSV administered is measured as focus forming units (FFU) per mL, as required by instant claims 1, 11, 22, 27, and 40-42 or that the intranasal administration is accomplished via nose drops or spray, recited in claim 5. Mueller et al. also do not teach administration is provided to a subject that is under the age of 18, 13, 7, or 2, or 18-49 year-olds, or at least 50 years of age, recited in instant claims 34, 38, and 39.
Moore ‘549 teach intranasal vaccination with a codon deoptimized RSV in varying doses 105 FFU, 104 FFU, and 103 FFU, per mL, see paragraphs [0046, 0169] and Figure 12. Paragraph [0157] of Moore ‘549 states that preferable intranasal administration is accomplished by drops or spray. In paragraph [0152] Moore ‘549 teach administration to subjects at two-months old, six-months old, one year old, and two years old. Moore ‘549 also teach administration to subjects over 55 years old and health care workers, day care workers, and family members of young children (generally 18-49 years old).
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered an effective amount of the codon deoptimized RSV of Mueller et al. in FFU/mL, as taught by Moore ‘549, because Baer et al. teach FFU is detected by intracellular viral proteins through tagged antibodies, providing increased sensitivity, decreased incubation times after infection, the ability to quantitate non-lytic viruses, compared to quantify virus by plaque formation, see “Basic plaque assays...”, above “Protocol”. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered an effective amount of the codon deoptimized RSV of Mueller et al. in FFU/mL, as taught by Moore ‘549, because both Mueller et al. and Moore ‘549 administer codon deoptimized RSV, see section 2.3 of Mueller et al. and paragraph [0046] and Figure 12 of Moore ‘549.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have intranasally administered the codon deoptimized RSV of Mueller et al. by drops or spray, as taught by Moore ‘549, to elicit mucosal immunity at the site of entry of the virus, see paragraph [0157]. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have intranasally administered the codon deoptimized RSV of Mueller et al. by drops or spray, as taught by Moore ‘549 because Moore ‘549 teach attenuated live virus vaccines are preferred for intranasal administration in paragraph [0157], which is what the codon deoptimized RSV of Mueller et al. is.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the codon deoptimized RSV of Mueller et al. to subjects at two-months old, six-months old, one year old, two years old, 18-49 years old, and subjects over 55 years old, as taught by Moore ‘549, to elicit and maintain sufficient levels of immunity in different age groups.
While Mueller et al. measure IgG-specific RSV neutralization titers in sections 2.3, 3.2, and Figure 2, Mueller et al. do not measure IgA, as recited in instant claim 1 or that the IgA immune response results in an increases of at least 2.4-fold, as recited in instant claims 27 and 42, or intranasally administering the second dose of RSV at about 28 days, as recited in instant claims 40-42.
Rostad et al. teach intranasally administering a codon deoptimized RSV (DB1) on day 0 and day 21, which is “about” 28 days, taught by Mueller et al. Rostad et al. teach an increase of IgA titers to approximately 23, which would be at least a 2.4 fold increase over zero IgA titers if compared prior to vaccination. See Figure 5D.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have administered the codon deoptimized RSV of Mueller et al. as first and second administrations, taught by Rostad et al., because Rostad et al. teach DB1 reduced challenge strain titers by over 99% in both the nasal wash and lung lavage specimens. Rostad et al. conclude that codon deoptimized RSV, DB1, is attenuated, highly immunogenic,
and efficacious at protecting against RSV challenge. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the codon deoptimized RSV of Mueller et al. as first and second administrations, taught by Rostad et al. to achieve a protective neutralizing titer of IgA because the RSV vaccines of Mueller et al. and Rostad et al. are codon deoptimized, see the abstract and “Importance”, Introduction, and Figure 2 of Rostad et al. and the last two paragraphs above “2. Methods” and section 2.2 of Mueller et al.
Mueller et al. do not teach or suggest that the codon deoptimized RSV comprises the sequence of SEQ ID NO: 1, recited in instant claims 33 and 40-42.
Published_Applications_NA_Main database 16-335-099-14 shares 100% sequence identity with instant SEQ ID NO: 1, see the alignment provided.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have used the sequence of LeNouen et al. as the RSV of Mueller et al. because LeNouen et al. teach the attenuated RSV is administered intranasally by spray or drops, see claims 40-42 and 56-59. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have used the sequence of LeNouen et al. as the RSV of Mueller et al. because both RSV recombinants of LeNouen et al. and Mueller et al. are codon deoptimized, see paragraphs [0025, 0060-0062] and Example 2 of LeNouen et al. and the last two paragraphs above “2. Methods” and section 2.2 of Mueller et al.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller et al., Moore ‘549, Baer et al., Rostad et al., and instant SEQ ID NO: 1 alignment with Published_Applications_NA_Main database 16-335-099-14 from USPgPub 20190233476 of LeNouen et al., as applied to claims 1-5, 7, 11, 15-17, 22, 27, 33, 34, and 38-42 above, and further in view of Meyers et al. (USPgPub 2020/0168205).
See the teachings of the references cited above. None of the references teach administering the RSV vaccine in four aliquots, as recited in instant claim 12, where each dose is administered to a first and second nostril with 10, 5-20, or 10-15 minutes between each dose, as required in claims 13 and 14.
Meyers et al. teach routes of intranasal administration provided in two 0.25 mL nasal sprays in each nostril (naris) with a 15-minute wait time between each bilateral administration, see paragraph [0297].
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have incorporated the intranasal regimen of Meyers et al. for administering the RSV vaccine of Mueller et al., Moore ‘549, Baer et al., Rostad et al., and LeNouen et al. with a reasonable expectation of success to ensure the vaccine is not lost through drip, sneeze, or blowing. In addition, a lag time of 5-15 minutes between administrations or bilateral administrations, would provide adequate time for intervention if the subject had a poor reaction to the vaccine, absent unexpected evidence to the contrary.
Conclusion
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/Shanon A. Foley/Primary Examiner, Art Unit 1671