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 .
1. Claims 1-40 as filed on October 19, 2022 are pending and under consideration.
Drawings
2. The drawings are objected to because Figures 1, 3, 4, 6, 7, and 9-14 are not fully legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
3. Claims 1-40 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 is drawn to a method of inducing an immune response in a subject in need thereof comprising administering the subject an effective amount of an antigen and adjuvant to induce an immune response against an antigen, the method comprising two or more of (i) slow prime delivery of antigen and/or adjuvant, a (ii) temporally delayed 2nd immunization, and (iii) a robust adjuvant. The claim has a broad step (administering the subject an effective amount of an antigen and adjuvant to induce an immune response against an antigen) and a narrow step (the method comprising two or more of (i) slow prime delivery of antigen and/or adjuvant, a (ii) temporally delayed 2nd immunization, and (iii) a robust adjuvant).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation: administering the subject an effective amount of an antigen and adjuvant to induce an immune response against an antigen; and the claim also recites: the method comprising two or more of (i) slow prime delivery of antigen and/or adjuvant, a (ii) temporally delayed 2nd immunization, and (iii) a robust adjuvant; which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Additionally, the second step does not require the administration of both an antigen and antigen as required by the first step in all of the various alternative permutations encompassed by the second step of claim 1. Thus, it is unclear if claim 1 requires administration of both an antigen and antigen in all of the alternatives claimed.
Therefore, for the above reasons, claim 1 and its dependent claims are indefinite.
Additionally, the terms "slow prime delivery", "temporally delayed 2nd immunization" and “robust adjuvant” in claim 1, “temporally extended”, “temporally extended exposure” in claims 2, 3 and 23, “cage-like” in claim 33, and “traditional prime and short boost of antigen and an adjuvant consisting of alum” in claims 29 and 30 are relative terms which render the claims indefinite. The terms “slow prime delivery", "temporally delayed 2nd immunization", “robust adjuvant” “cage-like nanoparticle”, and “traditional prime and short boost of antigen and an adjuvant consisting of alum” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification does not teach at what point the prime delivery is considered slow, how long the delay is for the 2nd immunization, when an adjuvant is considered robust, or how long the exposure can be extended or how much like a cage the nanoparticle must be. Similarly the specification does not teach at what point an immunization is considered a “traditional prime and short boost of antigen and an adjuvant consisting of alum”.
Section 2171 of the M.P.E.P. states
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of applicant or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
In the instant case of "slow prime delivery", "temporally delayed 2nd immunization", “robust adjuvant”, “temporally extended exposure”, “cage-like nanoparticle” and “traditional prime and short boost of antigen and an adjuvant consisting of alum”, one of skill in the art could find representative examples in the art which have been defined in such terms, however, it is unclear at what point one of skill in the art would be infringing on the claims without limitations as to the metes and bounds of "slow prime delivery", "temporally delayed 2nd immunization", “robust adjuvant”, “temporally extended exposure”, “cage-like nanoparticle” and/or “traditional prime and short boost of antigen and an adjuvant consisting of alum” and the amount of deviation acceptable under said terms.
Thus a "slow prime delivery" is interpreted to include any rate of delivery. A “temporally delayed 2nd immunization’ is interpreted to include any 2nd immunization. A “robust adjuvant” is interpreted to include any adjuvant. A “temporally extended exposure” is interpreted to include any exposure time. A “cage-like nanoparticle” is interpreted to include any nanoparticle capable of containing additional components like an adjuvant. A “traditional prime and short boost of antigen and an adjuvant consisting of alum” is interpreted to include any prime and boos of antigen with an adjuvant consisting of alum.
Claim Rejections - 35 USC § 102
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.
4. Claim(s) 1-14, 16, 19-24, 27-32 and 37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cirelli et al. (Cell May 16, 2019 177: 1153-1171, IDS), “Cirelli”.
Cirelli teaches that two independent methods of slow delivery immunization with soluble native-like HIV Env trimer BG505 Olio6CD4ko protein in a soluble ISCOM-class saponin adjuvant, Quil-A, of rhesus monkeys (RMs) resulted in more robust T follicular helper (TFH) cell responses and germinal center (GC) B cells with improved HIV Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous neutralizing antibodies (nAbs). See Summary, p. 1156-1st paragraph and p. e9- ISCOM-class saponin adjuvant.
Cirelli teaches that the adjuvant used for all the described studies was a ISCOM-like saponin nanoparticle comprised of self-assembled cholesterol phospholipid, DPPC, and quillaja saponin/Quil-A. See p. e9- ISCOM-class saponin adjuvant.
Cirelli teaches three delivery strategies were tested: conventional bolus immunization via subcutaneous (s.c.) injection (n = 9), 2-week s.c. nonmechanical osmotic pumps (Ops) (n = 4) and 4-week s.c. OPs (n = 4) (Figure 1A). All immunizations were given bilaterally in the left and right thighs. See p. 1156-1st paragraph and Fig. 1A, reproduced below.
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Cirelli teaches that the sustained delivery immunization enhance B-GC cell responses and higher nAb titers. See Figs. 1 and 3.
Cirelli teaches escalating dose immunization that enhance GC and nAb responses. Cirelli teaches the control group was given conventional bolus immunizations at week 0, week 10, and week 24, totaling 100 mg, 100 mg, and 300 mg of Olio6 native-like Env trimer protein, respectively, mixed with an ISCOM-class adjuvant. Escalating dose immunizations were administered as 7 injections over 2 weeks (Figure 6A), with a total antigen dose equivalent to that of the conventional bolus immunization group. See p. 1163-paragraph bridging the columns and Fig. 6A.
Cirelli teaches significantly higher frequencies of B-GC cells in draining lymph nodes were observed at week 5 in the escalating dos group compared with the conventional bolus immunization group (Figures 6B, 6C,and S7A). Escalating doe immunization resulted in significantly more Env specific B and B-GC cells after the first immunization. See p. 1163-right column and Fig. 6B-6E.
Cirelli teaches that the escalating dose animals were given seven injections of Olio6 and saponin adjuvant in each thigh over 12 days (on days 0, 2, 4, 6, 8, 10, 12 for each immunization). The total doses of Olio6 at each injection during the first two immunizations were: 0.2, 0.43, 1.16, 3.15, 8.56, 23.3, 63.2 mg (the doses per immunization site were 0.1, 0.215, 0.58, 1.575, 4.28, 11.65, 31.6 mg). The total doses of Olio6 at each injection during the third immunization were: 0.6, 1.29, 3.48, 9.45, 25.68, 69.9, 189.6 mg (the doses per immunization site were 0.3, 0.645, 1.74, 4.725, 12.84, 34.95, 94.8 mg). The total doses of saponin adjuvant at each injection during all immunizations were: 0.75, 1.61, 4.35, 11.81,32.1, 87.38, 237.0U (the doses per immunization site were 0.375, 0.805, 2.175, 5.905, 16.05, 43.69, 118.5U). See p. e9-2nd paragraph.
Cirelli teaches that the third escalating does set was administered at weeks 24, 25, and 26 after the first dose. See Fig. 6A.
5. Claim(s) 1-20 and 23-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2020/0085756 A1 (Irvine et al. Mar. 19, 2020, IDS), “Irvine”.
Irvine teaches non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided. See abstract.
Irvine teaches the nanocage adjuvants alone or more typically in combination with an antigen can be administered as a vaccine that includes a first (“prime”) and optionally one or more (“boost”) administrations. Thus in some embodiments, a vaccine is administered 2, 3, 4, or more times, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 days, weeks, months, or years apart. See ¶¶ 0198 and 0199.
Irvine teaches that the compositions are administered by subcutaneous, intramuscular, intradermal, subcutaneous, intravenous injection or by infusion with an infusion pump. See ¶¶ 0020 and 0134-0136 and Example 6.
Irvine teaches incorporating the compositions into polymeric implants, which can effect a sustained release of the composition to the immediate area of the implant. See ¶ 0136.
Regarding claims 9-14, it is noted that the claims further limit escalating dosing, but do not exclude the other alternatives of claim 5 from which the claims depend.
Irvine teaches administering the subject an effective amount of the antigen in the same or a separate admixture (e.g., pharmaceutical composition) as the nanocage adjuvant in the same or different routes. ¶¶ 0020 and 0154 and claims 32 and 35-37 and Example 6.
Irvine teaches that nanocage adjuvant including an additional adjuvant such as a TLR4 agonist is administered to a subject in need thereof in an effective amount to increase an antigen-specific antibody response (e.g., IgG, IgG2a, IgG1, or a combination thereof), increase a response in germinal centers (e.g., increase the frequency of germinal center B cells, increase frequencies and/or activation T follicular helper (Tfh) cells, increase B cell presence or residence in dark zone of germinal center or a combination thereof). See ¶¶ 0159, 0229-0232, 0264, Fig. 2A-2B, Fig 3A-D, Fig. 11A-C and claim 26.
Irvine teaches that suitable ratios for the lipid, additional adjuvant (e.g., TLR4 agonist), sterol, and saponin components are provided. For example, in a particular embodiment, the lipid: additional adjuvant (e.g., TLR4 agonist):sterol: saponin are in a molar ratio of 2.5:1:10:10, or a variation thereof wherein the molar ratio of any one or more of the lipid, additional adjuvant, sterol, and/or saponin is increased or decreased by any value greater than 0 and up to about 3. See ¶¶ 0012 and 0120 and claim 4.
Irvine teaches that the lipid is DPPC, the additional adjuvant is a natural or synthetic MPLA, the sterol is cholesterol, and the saponin is Quil A in a molar ratio of 2.5:1:10:10. See ¶¶ 0016, 0122, and 0207 and claim 20.
Irvine teaches that antigen can be a viral antigen including an antigen isolated from a coronavirus. See ¶¶ 0089-0091.
6. Claim(s) 1-21, 23-28, 30 and 37-40 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2023/0263882 A1 (Steinbuck et al. Aug. 24, 2023, filed June 25, 2021), “Steinbuck”.
Steinbuck teaches CpG-amphiphiles and corona virus antigens (e.g., a coronavirus spike protein, a peptide thereof, or a nucleic acid sequence encoding the same) for use in inducing an immune response in a subject, and methods of administering CpG-amphiphiles and coronavirus antigens (e.g., a coronavirus spike protein, a peptide thereof, a coronavirus nucleocapsid protein, a peptide thereof, or a nucleic acid sequence encoding the same) to induce an immune response in a subject. See abstract and ¶¶ 0005 and 0006.
Steinbuck teaches in some embodiments, the CpG-amphiphile and the coronavirus antigen or nucleic acid encoding the same are administered concurrently. In some embodiments, the CpG-amphiphile and the coronavirus antigen or nucleic acid encoding the same are administered sequentially. In some embodiments, the CpG-amphiphile is administered first, followed by administering of the coronavirus antigen or nucleic acid encoding the same. In some embodiments, the coronavirus antigen or nucleic acid encoding the same is administered first, followed by administering of CpG-amphiphile. See ¶¶ 0019, 0021, 0181, and 0207 and claims 1 and 38-42
Steinbuck teaches the CpG-amphiphile and the coronavirus antigen and the one or more additional therapeutics may be administered sequentially (e.g., 1 day apart, 2 days apart, 3 days apart, 1 week apart, 1 month apart, 6 months apart, or more) or substantially simultaneously (e.g., within 1 day). The CpG-amphiphile and the coronavirus antigen and the one or more additional therapeutics may be formulated in a single pharmaceutical composition or may be administered as separate pharmaceutical compositions. The CpG-amphiphile and the coronavirus antigen and the one or more additional therapeutics may be administered by the same route of administration or different routes of administration. The two or more agents may be administered at the same frequency or different frequencies. See ¶¶ 0207.
Regarding claims 6 and 7, it is noted that the claims further limit infusion, but do not exclude the other alternatives of claim 5 from which the claims depend.
Regarding claims 9-14, it is noted that the claims further limit escalating dosing, but do not exclude the other alternatives of claim 5 from which the claims depend.
Steinbuck teaches the dosage of the pharmaceutical compositions of the invention depends on factors including the route of administration and the physical characteristics, e.g., age, weight, general health, of the subject. Typically, the amount of a CpG-amphiphile and a coronavirus antigen (e.g., a coronavirus spike protein or a peptide thereof, and/or a coronavirus nucleocapsid protein or peptide thereof, or a nucleic acid sequence encoding the same) described herein contained within a single dose may be an amount that effectively induces an immune response in the subject without inducing significant toxicity. A pharmaceutical composition of the invention may include a dosage of a CpG-amphiphile and a coronavirus antigen (e.g., a coronavirus spike protein or a peptide thereof, and/or a coronavirus nucleocapsid protein or peptide thereof, or a nucleic acid sequence encoding the same) described herein ranging from 0.001 to 500 mg (e.g., 0.01, 0.05, 0.1, 0.2, 0.3, 0.5, 0.7, 0.8, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 50 mg, 100 mg, 250 mg, or 500 mg) and, in a more specific embodiment, about 0.1 to about 100 mg. The dosage may be adapted by the clinician in accordance with the different parameters of the subject. See ¶¶ 0177-0178.
Steinbuck teaches pharmaceutical compositions of the invention that contain a CpG-amphiphile and a coronavirus antigen (e.g., a coronavirus spike protein or a peptide thereof, and/or a coronavirus nucleocapsid protein or peptide thereof, or a nucleic acid sequence encoding the same) described herein may be administered to a subject in need thereof, for example, one or more times (e.g., 1-10 times or more) daily, weekly, monthly, biannually, annually, or as medically necessary. See ¶¶ 0180.
Steinbuck teaches the CpG-amphiphile and the coronavirus antigen (e.g., a spike protein, peptide thereof, nucleocapsid protein, or nucleic acid encoding the same) is administered subcutaneously, intranasally, intratracheally, or by inhalation during mechanical ventilation. In one embodiment, the CpG-amphiphile is administered subcutaneously. See ¶¶ 0022, 0169 and 0176.
Steinbuck teaches the humoral immune response induced in mice was determined for C57Bl/6J mice that were administered three doses of 10 μg of a coronavirus spike protein (SEQ ID NO: 3) in combination with 100 μg Alum, 1 nmol soluble CpG, or 1 nmol AMP-CpG. See ¶¶ 0350-0355 and Fig. 20-22. Steinbuck teaches that the coronavirus spike protein and AMP-CpG immunization enabled at least 10-fold dose sparing of coronavirus spike protein antigen for induction of neutralizing, high titer, and optimal Th1 profile antibody responses against coronavirus spike protein. See ¶ 0355.
Steinbuck teaches CpG-amphiphile and a coronavirus antigen can be administered in sustained release formulations. See ¶¶ 0173 and 0208.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
7. Claim(s) 1-38 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0085756 A1 (Irvine et al. Mar. 19, 2020, IDS), “Irvine” in view of Cirelli et al. (Cell May 16, 2019 177: 1153-1171, IDS), “Cirelli”.
Irvine teaches as set forth above, but does not teach escalating the dose of antigen and/or adjuvant.
Cirelli teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Irvine and Cirelli and escalate the dose of antigen and/or adjuvant because Cirelli teaches escalating the immunization doses enhances the GC and neutralizing Ab responses to immunization. Given the benefits of escalating the immunization doses taught by Cirelli, one would have been motivated to escalate the immunization doses of Irvine to enhance the GC and neutralizing Ab responses to immunization.
8. Claim(s) 1-40 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0085756 A1 (Irvine et al. Mar. 19, 2020, IDS), “Irvine” in view of Cirelli et al. (Cell May 16, 2019 177: 1153-1171, IDS), “Cirelli” as applied to claims 1-38 above, in further view of US 2023/0263882 A1 (Steinbuck et al. Aug. 24, 2023, filed June 25, 2021), “Steinbuck”.
Irvine and Cirelli teach as set forth above, but do not teach using a SARS-CoV-2 spike antigen.
Steinbuck teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Irvine, Cirelli and Steinbuck and use a SARS-CoV-2 spike antigen as antigen because Irvine teaches that antigen can be a viral antigen including an antigen isolated from a coronavirus and Steinbuck teaches that immunization with coronavirus spike protein and the AMP-CpG adjuvant enabled at least 10-fold dose sparing of coronavirus spike protein antigen for induction of neutralizing, high titer, and optimal Th1 profile antibody responses against coronavirus spike protein. Given the effectiveness of SARS-CoV-2 spike antigen at inducing an immune response in combination with an adjuvant, one would have been motivated to use the spike antigen to stimulate an immune response against SARS-CoV-2.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 1-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,547,672 B2 (Irvine et al. Jan 10, 2023) in view of US 2020/0085756 A1 (Irvine et al. Mar. 19, 2020, IDS), “Irvine” in view of Cirelli et al. (Cell May 16, 2019 177: 1153-1171, IDS), “Cirelli” as applied to claims 1-38 above, in further view of US 2023/0263882 A1 (Steinbuck et al. Aug. 24, 2023, filed June 25, 2021), “Steinbuck”.
The ‘672 claims are drawn to:
1. A non-liposome, non-micelle, porous, cage-like particle comprising a phospholipid, a sterol, a saponin, and a pattern recognition receptor (PRR) ligand comprising a lipid.
3. The particle of claim 2, wherein the porous, cage-like nanoparticle is about 30 nm to about 60 nm.
4. The particle of claim 1 comprising phospholipid:PRR ligand:sterol:saponin in a molar ratio of 2.5:1:10:10, or a variation thereof wherein the molar ratio of lipid, PRR ligand, sterol, saponin or any combination thereof is increased or decreased by any value between about 0 and about 3.
17. The particle of claim 1, wherein the phospholipid is DPPC, the PRR ligand is a natural or synthetic MPLA, the sterol is cholesterol, and the saponin is Quil A or QS-21.
18. The particle of claim 17, wherein the DPPC: MPLA: cholesterol: Quil A or DPPC:MPLA:cholesterol:QS-21 are in a molar ratio of 2.5:1:10:10.
22. A pharmaceutical composition comprising a plurality of the particle of claim 1 and a pharmaceutical carrier.
23. The pharmaceutical composition of claim 22, comprising an effective amount of the particles to increase an immune response in a subject in need thereof.
24. The pharmaceutical composition of claim 23, wherein the immune response is selected from the group consisting of increasing an antigen-specific antibody response, increasing a response in a germinal center, increasing plasma blast frequency, increasing inflammatory cytokine, increasing drainage of antigen from an injection site, increasing antigen accumulation in a lymph node, increasing permeability of a lymph node, increasing lymph flow, increasing antigen-specific B cell antigen uptake in a lymph nodes, or a combination thereof.
30. A method of treating a subject in need thereof comprising administering the subject the pharmaceutical composition of claim 22 in an effective amount to induce an immune response against an antigen.
31. The method of claim 30, wherein the antigen is derived from tumor cells or a microbe.
32. The method of claim 30, wherein the subject has or may develop a cancer or infection associated with tumor cells or microbe.
33. The method of claim 30 further comprising administering the subject an effective amount of the antigen.
34. The method of claim 33, wherein the antigen is in the same or a separate pharmaceutical composition from the particles.
35. The method of claim 30, wherein the particles alone or in combination with the antigen are administered to the subject by subcutaneous, intramuscular, intradermal, or intravenous injection.
The ‘672 claims teach as set forth above, but do not teach the temporal administration variations claimed or treating with a SARS-CoV-2 spike protein antigen.
Irvine, Cirelli, and Steinbuck teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘672 claims, Irvine, Cirelli, and Steinbuck and escalate the dose of antigen and/or adjuvant because Cirelli teaches escalating the immunization doses enhances the GC and neutralizing Ab responses to immunization. Given the benefits of escalating the immunization doses taught by Cirelli, one would have been motivated to escalate the immunization doses of the ‘672 claims to enhance the GC and neutralizing Ab responses to immunization.
Additionally it would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘672 claims, Irvine, Cirelli and Steinbuck and use a SARS-CoV-2 spike antigen as antigen because the ‘672 claims teach treating an infection, Irvine teaches that antigen can be a viral antigen including an antigen isolated from a coronavirus and Steinbuck teaches that immunization with coronavirus spike protein and the AMP-CpG adjuvant enabled at least 10-fold dose sparing of coronavirus spike protein antigen for induction of neutralizing, high titer, and optimal Th1 profile antibody responses against coronavirus spike protein. Given the effectiveness of SARS-CoV-2 spike antigen at inducing an immune response in combination with an adjuvant, one would have been motivated to use the spike antigen to stimulate an immune response against SARS-CoV-2.
10. Claims 1-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,246,097 B2 (Irvine et al, Mar. 11, 2025) in view of US 2020/0085756 A1 (Irvine et al. Mar. 19, 2020, IDS), “Irvine” in view of Cirelli et al. (Cell May 16, 2019 177: 1153-1171, IDS), “Cirelli” as applied to claims 1-38 above, in further view of US 2023/0263882 A1 (Steinbuck et al. Aug. 24, 2023, filed June 25, 2021), “Steinbuck”.
The ‘097 claims are drawn to:
1. A porous or perforated non-liposome, non-micelle nanoparticle comprising a phospholipid, a sterol, a saponin, and a TLR4 agonist lipopolysaccharide (LPS) or a lipid A derivative thereof.
2. The particle of claim 1, wherein the saponin comprises Quil A or QS-21.
3. The particle of claim 1, wherein the nanoparticle is about 30 nm to about 60 nm.
4. The particle of claim 1, wherein the phospholipid is 2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC).
5. The particle of claim 1, wherein the lipopolysaccharide (LPS) or lipid A derivative thereof is a natural or synthetic monophosphoryl lipid A (MPLA).
6. The particle of claim 5 comprising lipid: MPLA: sterol: saponin molar ratio of 2.5:1:10:10, or a variation thereof wherein the molar ratio of lipid, MPLA, sterol, saponin or any combination thereof is increased or decreased by any value between about 0 and about 3.
7. The particle of claim 5, wherein the MPLA is natural or synthetic 4′-monophosporyl lipid A (MPLA) or 3-O-deacylated monophosphoryl lipid A (3D-MPLA).
8. The particle of claim 1, wherein the sterol is cholesterol or a derivative thereof.
9. The particle of claim 1, wherein the saponin is a natural or synthetic saponin.
10. A method of making the particle of claim 1, comprising mixing the phospholipid, sterol, saponin, and lipopolysaccharide (LPS) or a lipid A derivative thereof in an aqueous carrier comprising detergent to form a solution and removing the detergent until the phospholipid, sterol, saponin, and lipopolysaccharide (LPS) or a lipid A derivative thereof self-assemble into porous or perforated nanoparticles.
11. A pharmaceutical composition comprising a plurality of the particle of claim 1 and a pharmaceutical carrier.
12. A method of treating a subject in need thereof comprising administering the subject the pharmaceutical composition of claim 11 in an effective amount to induce an immune response against an antigen.
13. A kit comprising a plurality of the particles of claim 1 in a lyophilized or dried form, or suspended in a pharmaceutically acceptable carrier.
14. The particle of claim 1, wherein the saponin is Quil A.
15. The particle of claim 14, wherein the sterol is cholesterol, the lipopolysaccharide (LPS) or a lipid A derivative thereof is MPLA, and the phospholipid is DPPC.
16. The particle of claim 1, the saponin is QS-21.
17. The particle of claim 16, wherein the sterol is cholesterol, the lipopolysaccharide (LPS) or a lipid A derivative thereof is MPLA, and the phospholipid is DPPC.
18. A porous or perforated non-liposome, non-micelle, cage-like nanoparticle comprising a phospholipid, cholesterol, QS-21, and MPLA.
19. The pharmaceutical composition of claim 11, further comprising an antigen.
20. The pharmaceutical composition of claim 19, wherein the antigen is derived from a source selected from the group consisting of a virus, bacterium, parasite, plant, protozoan, fungus, tissue and transformed cell.
The ‘097 claims teach as set forth above, but do not teach the temporal administration variations claimed or treating with a SARS-CoV-2 spike protein antigen.
Irvine, Cirelli, and Steinbuck teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘097 claims, Irvine, Cirelli, and Steinbuck and escalate the dose of antigen and/or adjuvant because Cirelli teaches escalating the immunization doses enhances the GC and neutralizing Ab responses to immunization. Given the benefits of escalating the immunization doses taught by Cirelli, one would have been motivated to escalate the immunization doses of the ‘097 claims to enhance the GC and neutralizing Ab responses to immunization.
Additionally it would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘097 claims, Irvine, Cirelli and Steinbuck and use a SARS-CoV-2 spike antigen as antigen because the ‘097 claims teaches using an antigen from a virus, Irvine teaches that antigen can be a viral antigen including an antigen isolated from a coronavirus and Steinbuck teaches that immunization with coronavirus spike protein and the AMP-CpG adjuvant enabled at least 10-fold dose sparing of coronavirus spike protein antigen for induction of neutralizing, high titer, and optimal Th1 profile antibody responses against coronavirus spike protein. Given the effectiveness of SARS-CoV-2 spike antigen at inducing an immune response in combination with an adjuvant, one would have been motivated to use the spike antigen to stimulate an immune response against SARS-CoV-2.
Conclusion
11. Claims 1-40 are rejected. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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/PETER J REDDIG/ Primary Examiner, Art Unit 1646
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