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 .
Claim Status
Claims 25-37 have been cancelled, as requested in the preliminary amendment filed on 04/15/2024. Following the amendment, claims 1-24 are pending in the instant application.
Claims 1-24 are under examination in the instant office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 1-24 have an effective filing date of February 26, 2021 corresponding to PRO 63/154,469.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Pages 39-40. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
It is specifically noted that claims 1 and 20 recite the following claim language: “comprising, consisting essentially of, or consisting of”. Under the broadest reasonable interpretation (BRI), it is noted that above-recited claim language is being interpreted as open claim language, wherein limitations “comprising, consisting essentially of, or consisting of” a recited element/elements are being interpreted as “comprising” said element/elements.
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 2, 9-12, 14-20, and 22 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.
Regarding claims 2, 14, 20, and 22, it is noted that 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 2 recites the broad recitation “wherein the average molecular weight of the PEG in the PEGylated lipid ranges from about 750 Daltons to about 5000 Daltons”, and the claim also recites “optionally about from about 750 Daltons to 2000 Daltons” which is the narrower statement of the range/limitation. Claim 14 recites the broad recitation “wherein the liposome further comprises at least one TLR agonist”, and the claim also recites “optionally at least two TLR agonists” which is the narrower statement of the range/limitation. Claim 17 recites the broad recitation “wherein: R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl”, and the claim also recites “optionally wherein R1, R3, R5 and R6 are C11 alkyl; and R2 and R4 are C13 alkyl” which is the narrower statement of the range/limitation. Claim 20 recites the broad recitation “wherein the SARS-CoV-2 antigen is a Spike protein antigen”, and the claim also recites “optionally a spike protein antigen comprising, consisting essentially of, or consisting of SEQ ID NO: 3 or an antigenic fragment thereof” which is the narrower statement of the range/limitation. Claim 22 recites the broad recitation “wherein the pharmaceutically acceptable carrier, excipient, and/or diluent is pharmaceutically acceptable for use in a mammal”, and the claim also recites “optionally a human” which is the narrower statement of the range/limitation. The claims are therefore 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.
Regarding claims 9-12 and 14-19, the claims all recite the limitation "the liposome". There is insufficient antecedent basis for this limitation in the claim. More specifically, independent claim 1 recites a “PEGylated liposomal adjuvant” which comprises, generally, (a) a cholesterol, (b) a non-PEGylated neutral lipid, and (c) a PEGylated lipid; however, independent claim 1 does not recite a singular “liposome”, and as such it is unclear as to what the recitation of “the liposome” is intended to refer to.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over:
(1) WO 2017/200957 A1;
(2) US 11,266,602;
(3) US 12,318,484; or
(4) US 2025/0241857 A1
each in view of non-patent literature by Zhang et. al. (Vaccines, 2020, 8(153), 1-12; herein after referred to as "Zhang"), US 10,787,501 (herein after referred to as "Babb"), and non-patent literature by Lei et. al. (Signal Transduction and Targeted Therapy, 2020, 5(291), 1-2; herein after referred to as “Lei”). It is specifically noted that US 11,266,602 corresponds to the US filing of WO 2017/200957 A1; US 12,318,484 is a continuation of US 11,266,602; and US 2025/0241857 A1 is a continuation of US 12,318,484. As such, WO 2017/200957 A1, US 11,266,602, US 12,318,484 and US 2025/0241857 A1 all have identical disclosures. The disclosure of WO 2017/200957 A1 (herein after referred to as "Fox") is the disclosure relied upon below.
Fox teaches that liposomes are attractive vaccine delivery vehicles due to the ability to tailor the liposome composition to achieve desired lipid concentration, charge, size, and distribution or targeting of antigen and adjuvant, but indicates that while numerous liposome-based systems have been evaluated including anionic, cationic, and neutral liposomes, not all liposomes are created equal; Fox notes that (i) cationic lipid liposome formulations are toxic, (ii) many neutral liposomes are unstable ex vivo and either grow in size over time or fall apart immediately after manufacture, and (iii) anionic liposomes have charge limitations that affect their ability to deliver various antigens and fuse with cellular membranes (Paragraph 0005). Other liposomes contain synthetic lipids or block copolymers which may exert effects on the immune system itself; cholesterol-based liposome formulations are ideal in that cholesterol is a natural component of human cell membranes, and when combined with other colipids, such as DOTAP and DOPC, forms stable cationic nanoparticles of approximately 100-200 nm with desirable polydispersity indexes of around 0.3 (Id.). Various strategies have been employed to improve liposomal formulations for use as vaccine formulations including PEGylation strategies, but no clear formulation has been developed that both overcomes the problems associated with the stability and toxicities of known liposomes, and can effectively improve the quality of immune response (Id.); thus the invention addresses the need to develop PEGylated liposomes that are stable, manufacturable, compatible with lipid-based antigens and adjuvants, and small in size, for vaccines, therapeutics, and diagnostics wherein, more specifically, in the realm of vaccines, there is especially a need to provide such liposomes in conjunction with adjuvants that can enhance an immune response and vaccinations for influenza, enteric diseases (such as amebiasis), tuberculosis, HIV, cancer, and hepatitis, for example, could benefit from the development of such liposomes (Paragraph 0006). The PEGylated liposomes of the invention comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less; the PEGylated liposomes are stable and are capable of delivery of an agent for the generation of an immune response wherein the liposome stability allows for delivery to immune cells, for the generation of an immune response (Paragraph 0009). The size of the PEGylated liposomes present in the composition ranges from about 1 nm to about 450nm, and the size remains stable at varying temperatures, and over time; the PEGylated liposomes are stable and display little to no aggregation, or reduced aggregation, and are amenable to a terminal sterilization step (i.e., are thermostable) prior to vialing (Id.). The invention provides a liposome comprising: (a) a cholesterol; (b) a non-PEGylated neutral lipid; and (c) a PEGylated lipid, wherein the average molecular weight of the PEG in the PEGylated lipid (i) is about 5000 Daltons or less, (ii) ranges from about 750 Daltons to about 5000 Daltons, (iii) is about 2000 Daltons or less, or (iv) is about 750 Daltons (Paragraph 0010). The lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE (i.e., zwitterionic/neutral lipids); in some embodiments, the lipid component of the PEGylated lipid is DSPE or DPPE (Id.). the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; in some embodiments, the non-PEGylated neutral lipid is DPPC (Id.). In some embodiments the liposome is stable; the liposome is stable for at least 1 month at temperatures of about 2-8 oC, about 25 oC, and/or about 37 oC (Id.). The polydispersity index of the liposome is maintained at about 0.3 or less, and the size of the liposome is maintained at less than or about 450 nm (Id.). In some embodiments, the molar percentage (mol%) of PEGylated lipid in the liposome ranges from about 1 mol% to about 25 mol%, the mol% of cholesterol in the liposome ranges from about 1 mol% to about 50 mol%, and/or the mol% of non-PEGylated lipid in the liposome ranges from about 45 mol% to about 98 mol% (Id.). In some embodiments, the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8; in other embodiments the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 18:5.5:3 (Id.). In additional embodiments, the liposome further comprises at least one TLR agonist, wherein the TLR agonist comprises a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR6 agonist, a TLR7 agonist, a TLR8 agonist, a TLR7/8 agonist, or a TLR9 agonist; in some embodiments the TLR agonist comprises TLR4, SLA, GLA, 3D-MPL, R837, or R848 and/or the TLR agonist comprises a hydrophobic tail (Id.). A TLR7/8 agonist comprises 3M-052 or R848; a TLR4 agonist comprises 3D-MPL,
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GLA, or a synthetic GLA of the formula reproduced below (Paragraphs 0010-0011):
It is further noted that a synthetic GLA may have the structure of Formula (VI), as shown below:
wherein R1, R3, R5 and R6 are C11-C20 alkyl, and R2 and R4 are C12-C20 alkyl or, in a more specific embodiment, R1, R3, R5 and R6 are C11 alkyl, and R2 and R4 are C13 alkyl (Paragraphs 0115-0117). In some embodiments, the liposome comprises a TLR4 agonist and a TLR7/8 agonist; in some embodiments, the liposome comprises GLA and 3M-052 (Paragraph 0011). In some embodiments, the liposome further comprises at least one agent, wherein the agent comprises a polypeptide, a polynucleotide, an antigen, an adjuvant, a diagnostic agent, a therapeutic agent, or an organism; exemplary antigens include amebiasis-related antigen, LecA, influenza-related antigens, tuberculosis-related antigen, hepatitis virus-related antigen, an HIV-related antigen, or a cancer-related antigen (Id.). The invention further provides compositions comprising the liposomes of the invention, wherein the composition comprises a pharmaceutically acceptable carrier, excipient, or diluent; in some embodiments the composition is a vaccine, therapeutic, or diagnostic (Paragraph 0012). In methods of the invention, the liposomes or compositions of the invention are administered to a human (i.e., acceptable for use in mammals, including humans) (Paragraph 0016). The liposomes of the invention are stable at various temperature ranges: they are amenable to a terminal sterilization step (i.e., are thermostable) prior to vialing (Paragraph 0009) and are stable at 0-8 °C (Paragraph 0212), 8-20 °C (Paragraph 0213), 20-30 °C (Paragraph 0214), 30-40 °C (Paragraph 0215), and 40-62 °C (Paragraph 0216). Additionally, pharmaceutical compositions of the invention may be formulated as a lyophilizate using appropriate excipient solutions as diluents (Paragraph 0242).
However, while Fox discloses liposome compositions comprising agents including antigens (e.g., viral antigens), Fox does not disclose combining the disclosed liposomal adjuvant with an antigen that is a SARS-CoV-2 antigen that is a Spike protein antigen comprising SEQ ID NO: 3 or an antigenic fragment thereof. These deficiencies are remedied by Zhang, Babb, and Lei.
Zhang teaches that in December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a serious pandemic in China and other countries worldwide; there is no effective means to prevent the infection (Abstract). Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases; several countries, companies, and institutions announced their programs and progress on vaccine development against the virus, and the authors review the progress and prospects in the field of vaccine development against SARS-CoV-2 (Id.). SARS-CoV-2 is a positive-strand RNA virus that belongs to the group of Betacoronaviruses; the
genome of SARS-CoV-2 is approximately 29,700 nucleotides long and shares 79.5% sequence identity with SARS-CoV and it has a long ORF1ab polyprotein at the 5’ end, which encode 15 or 16 non-structural proteins, and the 3’ end of the genome encodes 4 major structural proteins, including the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein (see Figure 1); SARS-CoV-2 binds to the receptor angiotensin converting enzyme 2 (ACE2) on host cell for the virus entry and subsequent pathogenesis, resulting in severe respiratory illness with symptoms of fever, cough, and shortness of breath, and severe cases can be fatal (Page 1, Introduction). Zhang further teaches that Spike protein (S protein) is the most promising antigen for SARS-CoV-2 vaccine research: (i) it is surface exposed and is able to be directly recognized by the host immune system; (ii) it mediates the interaction with host cell by binding to the receptor ACE2, which is essential for subsequent virus entry to target cells and causing subsequent pathogenicity; and (iii) the homologue proteins were already used for vaccine development against SARS-CoV and MERS-CoV, and were proved to be effective (Page 2, Section 2.2). The structure of the SARS-CoV-2 S trimer in the pre-fusion conformation and the RBD domain in complex with ACE2 has been successfully determined, which has provided valuable information for vaccine design based on this protein; so far, the potential fragments of S protein for use as antigens in vaccine development include the full-length S protein, the RBD domain, the S1 subunit, NTD, and FP (Page 3, First Partial Paragraph). Since the RBD of S protein directly interacts with the ACE2 receptor on host cells, RBD immunization induced specific antibodies may block this recognition and thus effectively prevent the invasion of the virus; most of SARS-CoV-2 subunit vaccines currently under development use RBD as the antigen (Page 3, Section 2.2.2). The RBD domain is relatively conserved as compared with S1 subunit and was reported to contain multiple conformational neutralizing epitopes, making it more suitable for vaccine development (Id.).
Babb provides antibodies and antigen-binding fragments that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections) (Abstract). In view of the continuing threat to human health, there is an urgent need for preventive and therapeutic antiviral therapies for SARS-CoV-2 control; because this virus uses its spike glycoprotein for interaction with the cellular receptor ACE2 and the serine protease TMPRSS2 for entry into a target cell, this spike protein represents an attractive target for antibody therapeutics (Column 1, Lines 49-61). In particular, fully human antibodies that specifically bind to the SARS-CoV-2-Spike protein (SARS-CoV-2-S) with high affinity and that inhibit virus infectivity could be important in the prevention and treatment of COVID-19 (Id.). The invention provides neutralizing human antigen-binding proteins that specifically bind to SARS-CoV-2-S, for example, antibodies or antigen-binding fragments thereof (Column 2, Lines 8-11). It is noted that Babb further characterized the epitopes to which the antibodies of the invention bind, and thus identifies antigenic fragments of the SARS-CoV-2-Spike protein, specifically antigenic fragments of the RBD domain (Columns 91-94, Tables 17-28). For example, mAb10898 bound residues 467-513 of the RBD, corresponding to Babb SEQ ID NO: 835 (DISTEIYQAGSTPCNGVEGFNCYFPL QSYGFQPTNGVGYQPYRVVVL) (Column 92, Lines 7-16); Babb SEQ ID NO: 835 is a 100% match to instant SEQ ID NO: 3 residues 454-500. As an additional example, mAb10987 bound residues 432-452 of the RBD, corresponding to Babb SEQ ID NO: 836 (CVIAWNSNNLDSKV GGNYNYL); Babb SEQ ID NO: 836 is a 100% match to instant SEQ ID NO: 3 residues 419-439.
Lei teaches that the worldwide outbreak of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection has urged the investigation of preventive vaccines; recently, the authors’ team has developed a recombinant protein vaccine, targeting receptor binding domain (RBD) of the spike protein (S-RBD) of SARS-CoV-2, which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge (Page 1, Column 1, First Paragraph). The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity; therefore, to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity, the authors investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2 (Id.). Notably, the three cationic nanocarriers studied included polyethyleneimine (PEI), N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) (i.e., cationic lipid), and Chitosan were investigated for their adjuvant effects (Page 1, Column 1, Second Paragraph). Cationic nanocarriers were potent adjuvants for mucosal and intramuscular vaccination of the recombinant RBD vaccine of SARS-CoV-2; the cationic nanocarriers improved the RBD-induced humoral immunity and also enhanced the cellular immune response in comparison to control groups, wherein these effects may be partially related to the increased antigen uptake and activation of DCs (Page 2, Column 1, Second Paragraph). Thus, Lei specifically teaches that liposomal adjuvants are effective in combination with S-RBD antigen in the context of immune response/vaccination.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant invention was filed to make a composition capable of eliciting an anti-SARS-CoV-2 immune response in a subject, wherein the composition generally comprises a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof) and a PEGylated liposomal adjuvant. One of ordinary skill in the art would have been motivated to modify the liposome compositions taught by Fox wherein the antigen used for eliciting an immune response is a SARS-CoV-2 antigen that is a Spike protein (i.e., S-RBD antigen) in order to develop a composition/vaccine that would reasonably be expected to be effective at producing an immune response against SARS-CoV-2, as suggested by Zhang, Babb, and Lei.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
In the instant case, it is noted that:
(1) Fox discloses stable liposome compositions capable of use in humans to elicit immune responses, wherein said liposome compositions comprise: (i) an antigen (e.g., viral antigens), (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, thermostability, TLR agonist structures, and lyophilized products, wherein said liposome compositions are identified as being advantageous in the delivery of agents to produce an immune response.
(2) Zhang identifies a need to develop effective agents (e.g., vaccines) against SARS-CoV-2, and identifies that the Spike protein of SARS-CoV-2 is the most promising antigen in SARS-CoV-2 vaccine research and more specifically indicates the RBD domain is a commonly used antigen.
(3) Babb discloses neutralizing antibodies that specifically bind to SARS-CoV-2 Spike protein useful in preventative and therapeutic approaches wherein Babb further characterizes the specific epitopes that said antibodies bind; more specifically Babb identifies antigenic epitopes within the RBD of the SARS-CoV-2 Spike protein that are specifically bound by the antibodies wherein said antigenic epitopes are comprised within instant SEQ ID NO: 3.
(4) Lei discloses that using the SARS-CoV-2 S-RBD antigen with liposomal adjuvants, in the context of vaccination, specifically increased RBD-induced humoral immunity and also enhanced cellular immune response.
Thus, to one of ordinary skill in the art, it would have been obvious to try and modify the liposome compositions of Fox such that a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof) could be used, as suggested by Zhang, Babb, and Lei, wherein said liposome composition would reasonably be expected to be capable of eliciting an immune response against said SARS-CoV-2 antigen, as suggested by Fox, Zhang, Babb, and Lei, such that the liposome composition would be an effective approach to SARS-CoV-2 vaccination and preventing infection.
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.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 12-14, 16-17, and 20-21 of U.S. Patent No. 11,266,602 (herein after referred to as “first reference patent”) in view of WO 2017/200957 A1 (herein after referred to as "Fox"), non-patent literature by Zhang et. al. (Vaccines, 2020, 8(153), 1-12; herein after referred to as "Zhang"), U.S. 10,787,501 (herein after referred to as "Babb"), and non-patent literature by Lei et. al. (Signal Transduction and Targeted Therapy, 2020, 5(291), 1-2; herein after referred to as “Lei”).
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First reference patent claim 1 is drawn to a liposome comprising: an antigen; a cholesterol; a non-PEGylated neutral lipid; a PEGylated lipid, wherein an average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons, wherein a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3; and agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and wherein the GLA comprises a synthetic GLA of formula:
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or a pharmaceutically acceptable salt thereof; or a synthetic GLA of formula (VI):
or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl. Claims 2-7 further limit claim 1 wherein, respectively: (i) the lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (ii) the lipid component of the PEGylated lipid comprises a C14 alkyl chain, a C16 alkyl chain, or a C18 alkyl chain; (iii) the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (iv) the non-PEGylated neutral lipid comprises a C14 alkyl chain, a C16 alkyl chain, or a C18 alkyl chain; (v) a polydispersity index of the liposome is maintained at about 0.3 or less; and (vi) a size of the liposome is less than or about 450 nm. First reference patent claim 12 is drawn to a liposome comprising: an antigen; a cholesterol; non-PEGylated neutral lipid comprising DMPC, DPPC, DSPC, or DOPC; a PEGylated lipid comprising DMPE, DPPE, or DSPE that is PEGylated with a PEG having an average molecular weight of about 2000 Daltons, wherein a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8; and agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and
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wherein the GLA comprises a synthetic GLA of formula:
or a pharmaceutically acceptable salt thereof; or a synthetic GLA of formula (VI):
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or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl. Claim 13 limits the liposome of claim 1 wherein the cholesterol is present at about 1-50 mol %, the non-PEGylated neutral lipid is present at about 45-98 mol %, and the PEGylated lipid is present at about 1-25 mol %; claim 14 limits the liposome of claim 13 wherein the cholesterol is present at about 50 mol %, the non-PEGylated neutral lipid is present at about 45 mol %, and the PEGylated lipid is present at about 5 mol %. Claims 16 limits the liposome of claim 12 wherein the cholesterol is present at about 1-50 mol %, the non-PEGylated neutral lipid is present at about 45-98 mol %, and the PEGylated lipid is present at about 1-25 mol %; claim 17 limits the liposome of claim 16 wherein the cholesterol is present at about 50 mol %, the non-PEGylated neutral lipid is present at about 45 mol %, and the PEGylated lipid is present at about 5 mol %. Claims 20 and 21 further limit the liposome of claim 1 and claim 12, respectively, wherein R1, R3, R5 and R6 are C11 alkyl and R2 and R4 are C13 alkyl. Thus, the first reference patent reads directly on the liposomes of instant claims 1-19.
However, the first reference patent does not claim: (i) a SARS-CoV-2 antigen (e.g., Spike protein); (ii) compositions for eliciting an immune response to SARS-CoV-2; (iii) compositions of liposomes comprising pharmaceutically acceptable carriers, excipients, and/or diluents for use in a mammal (e.g., a human); (iv) a composition of liposomes that is a vaccine; nor (v) a composition of liposomes that are in thermostable lyophilized form. These deficiencies are remedied by Fox, Zhang, Babb, and Lei whose teachings are detailed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant invention was filed to make a composition capable of eliciting an anti-SARS-CoV-2 immune response in a subject, wherein the composition generally comprises a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof) and a PEGylated liposomal adjuvant. One of ordinary skill in the art would have been motivated to modify the liposome of the first reference patent such that the liposome was comprised within a composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used for eliciting an immune response is a SARS-CoV-2 antigen that is a Spike protein in order to develop a composition/vaccine that would reasonably be expected to be effective at producing an immune response against SARS-CoV-2, as suggested by Zhang, Babb, and Lei.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
In the instant case, it is noted that:
(1) The first reference patent claims liposomes that comprise: (i) an antigen, (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, and TLR agonist structures. Fox discloses stable liposome compositions capable of use in humans to elicit immune responses, wherein said liposome compositions comprise: (i) an antigen (e.g., viral antigens), (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, thermostability, TLR agonist structures, and lyophilized products, wherein said liposome compositions are identified as being advantageous in the delivery of agents to produce an immune response.
(2) Zhang identifies a need to develop effective agents (e.g., vaccines) against SARS-CoV-2, and identifies that the Spike protein of SARS-CoV-2 is the most promising antigen in SARS-CoV-2 vaccine research and more specifically indicates the RBD domain is a commonly used antigen.
(3) Babb discloses neutralizing antibodies that specifically bind to SARS-CoV-2 Spike protein useful in preventative and therapeutic approaches wherein Babb further characterizes the specific epitopes that said antibodies bind; more specifically Babb identifies antigenic epitopes within the RBD of the SARS-CoV-2 Spike protein that are specifically bound by the antibodies wherein said antigenic epitopes are comprised within instant SEQ ID NO: 3.
(4) Lei discloses that using the SARS-CoV-2 S-RBD antigen with liposomal adjuvants, in the context of vaccination, specifically increased RBD-induced humoral immunity and also enhanced cellular immune response.
Thus, to one of ordinary skill in the art, it would have been obvious to try and modify the liposome of the first reference patent such that the liposome was comprised within a composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used is a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof), as suggested by Zhang, Babb, and Lei, wherein said liposome composition would reasonably be expected to be capable of eliciting an immune response against said SARS-CoV-2 antigen, as suggested by Fox, Zhang, Babb, and Lei, such that the liposome composition would be an effective approach to SARS-CoV-2 vaccination and preventing infection.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 9-14 of U.S. Patent No. 12,318,484 (herein after referred to as “second reference patent”) in view of WO 2017/200957 A1 (herein after referred to as "Fox"), non-patent literature by Zhang et. al. (Vaccines, 2020, 8(153), 1-12; herein after referred to as "Zhang"), U.S. 10,787,501 (herein after referred to as "Babb"), and non-patent literature by Lei et. al. (Signal Transduction and Targeted Therapy, 2020, 5(291), 1-2; herein after referred to as “Lei”).
Claim 1 of the second reference patent is drawn to a composition comprising: an antigen; and a liposome comprising: a cholesterol; a non-PEGylated neutral lipid; a PEGylated lipid, wherein an average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons, wherein a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3; and agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and wherein the GLA comprises a synthetic GLA of formula:
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or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl. Claims 2-7 further limit the composition of claim 1 wherein, respectively: (i) the lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (ii) the lipid component of the PEGylated lipid comprises a C14 alkyl chain, a C16 alkyl chain, or a C18 alkyl chain; (iii) the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (iv) the non-PEGylated neutral lipid comprises a C14 alkyl chain, a C16 alkyl chain, or a C18 alkyl chain; (v) R1, R3, R5 and R6 are C11 alkyl and R2 and R4 are C13 alkyl; and (vi) the synthetic GLA has the formula:
or a pharmaceutically acceptable salt thereof. Claims 9-11 and 13-14 further limit the composition of claim 1 wherein, respectively: (i) the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8; (ii) the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 18:5.5:3; (iii) the cholesterol is present at about 1-50 mol %, the non-PEGylated neutral lipid is present at about 45-98 mol %, and the PEGylated lipid is present at about 1-25 mol %; (iv) a polydispersity index of the liposome is maintained at about 0.3 or less; and (v) a size of the liposome is less than or about 450 nm. Claim 12 further limits the composition of claim 11, wherein the cholesterol is present at about 50 mol %, the non-PEGylated neutral lipid is present at about 45 mol %, and the PEGylated lipid is present at about 5 mol %. Thus, the second reference patent reads directly on the liposomes of instant claims 1-19.
However, the second reference patent does not claim: (i) a SARS-CoV-2 antigen (e.g., Spike protein); (ii) compositions for eliciting an immune response to SARS-CoV-2; (iii) compositions of liposomes comprising pharmaceutically acceptable carriers, excipients, and/or diluents for use in a mammal (e.g., a human); (iv) a composition of liposomes that is a vaccine; nor (v) a composition of liposomes that are in thermostable lyophilized form. These deficiencies are remedied by Fox, Zhang, Babb, and Lei whose teachings are detailed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant invention was filed to make a composition capable of eliciting an anti-SARS-CoV-2 immune response in a subject, wherein the composition generally comprises a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof) and a PEGylated liposomal adjuvant. One of ordinary skill in the art would have been motivated to modify the liposome compositions/liposomes of the second reference patent such that the liposome was comprised within a pharmaceutical composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used for eliciting an immune response is a SARS-CoV-2 antigen that is a Spike protein in order to develop a composition/vaccine that would reasonably be expected to be effective at producing an immune response against SARS-CoV-2, as suggested by Zhang, Babb, and Lei.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
In the instant case, it is noted that:
(1) The second reference patent claims liposome compositions that comprise: (i) an antigen, (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, and TLR agonist structures. Fox discloses stable liposome compositions capable of use in humans to elicit immune responses, wherein said liposome compositions comprise: (i) an antigen (e.g., viral antigens), (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, thermostability, TLR agonist structures, and lyophilized products, wherein said liposome compositions are identified as being advantageous in the delivery of agents to produce an immune response.
(2) Zhang identifies a need to develop effective agents (e.g., vaccines) against SARS-CoV-2, and identifies that the Spike protein of SARS-CoV-2 is the most promising antigen in SARS-CoV-2 vaccine research and more specifically indicates the RBD domain is a commonly used antigen.
(3) Babb discloses neutralizing antibodies that specifically bind to SARS-CoV-2 Spike protein useful in preventative and therapeutic approaches wherein Babb further characterizes the specific epitopes that said antibodies bind; more specifically Babb identifies antigenic epitopes within the RBD of the SARS-CoV-2 Spike protein that are specifically bound by the antibodies wherein said antigenic epitopes are comprised within instant SEQ ID NO: 3.
(4) Lei discloses that using the SARS-CoV-2 S-RBD antigen with liposomal adjuvants, in the context of vaccination, specifically increased RBD-induced humoral immunity and also enhanced cellular immune response.
Thus, to one of ordinary skill in the art, it would have been obvious to try and modify the liposome composition/liposomes of the second reference patent such that the liposome was comprised within a pharmaceutical composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used is a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof), as suggested by Zhang and Babb, wherein said liposome composition would reasonably be expected to be capable of eliciting an immune response against said SARS-CoV-2 antigen, as suggested by Fox, Zhang, and Babb, such that the liposome composition would be an effective approach to SARS-CoV-2 vaccination and preventing infection.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-13, 17, and 23-28 of copending Application No. 19/027,710 (herein after referred to as “reference application”) in view of WO 2017/200957 A1 (herein after referred to as "Fox"), non-patent literature by Zhang et. al. (Vaccines, 2020, 8(153), 1-12; herein after referred to as "Zhang"), U.S. 10,787,501 (herein after referred to as "Babb"), and non-patent literature by Lei et. al. (Signal Transduction and Targeted Therapy, 2020, 5(291), 1-2; herein after referred to as “Lei”).
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Claim 1 of the reference application is drawn to a composition comprising: an antigen; and a liposome comprising: a cholesterol; a non-PEGylated neutral lipid; and a PEGylated lipid, wherein the average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons; and agonists comprising GLA and 3M-052 wherein the GLA comprises a synthetic GLA of formula:
or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl. Claims 4-13 further limit the composition of claim 1 wherein, respectively: (i) the lipid component of the PEGylated lipid comprises a neutral lipid; (ii) the lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (iii) the lipid component of the PEGylated lipid is DSPE or DPPE; (iv) the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (v) the non-PEGylated neutral lipid is DPPC; (vi) the liposome is stable for at least 1 month at a temperature of about 2 °C to about 8 °C; (vii) the polydispersity index of the liposome is maintained at about 0.3 or less; (viii) the size of the liposome less than or about 450 nm; (ix) the molar percentage (mol %) of the PEGylated lipid in the liposome ranges from about 1 mol % to about 25 mol %, the mol % of cholesterol in the liposome ranges from about 1 mol % to about 50 mol % and the mol % of non-PEGylated lipid in the liposome ranges from about 45 mol % to about 98 mol %; and (x) the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3. Claim 17 further limits
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the composition of claim 1, wherein the synthetic GLA has the formula:
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or a pharmaceutically acceptable salt thereof; or a synthetic GLA of formula (VI):
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or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl, preferably R1, R3, R5 and R6 are C11 alkyl; and R2 and R4 are C13 alkyl. Claim 23 further limits the composition of claim 1, wherein the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 59-69% non-pegylated neutral lipid, about 21-34% cholesterol, and about 5-10% PEGylated lipid. Claim 24 is drawn to a liposome comprising: a cholesterol; a non-PEGylated neutral lipid; and a PEGylated lipid, wherein the average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons; and agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and wherein the GLA comprises a synthetic GLA of formula:
or a pharmaceutically acceptable salt thereof, wherein R1, R3, R5 and R6 are C11-C20 alkyl; and R2 and R4 are C12-C20 alkyl. Claims 25-28 further limit the liposome of claim 24 wherein, respectively: (i) the lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (ii) the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE; (iii) the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3; (iv) the lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 59-69% non-pegylated neutral lipid, about 21-34% cholesterol, and about 5-10% PEGylated lipid. Thus, the reference application reads directly on the liposomes/compositions of instant claims 1-19.
However, the reference application does not claim: (i) a SARS-CoV-2 antigen (e.g., Spike protein); (ii) compositions for eliciting an immune response to SARS-CoV-2; (iii) compositions of liposomes comprising pharmaceutically acceptable carriers, excipients, and/or diluents for use in a mammal (e.g., a human); (iv) a composition of liposomes that is a vaccine; nor (v) a composition of liposomes that are in thermostable lyophilized form. These deficiencies are remedied by Fox, Zhang, Babb, and Lei, whose teachings are detailed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the instant invention was filed to make a composition capable of eliciting an anti-SARS-CoV-2 immune response in a subject, wherein the composition generally comprises a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof) and a PEGylated liposomal adjuvant. One of ordinary skill in the art would have been motivated to modify the liposome compositions/liposomes of the reference application such that the liposome was comprised within a pharmaceutical composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used for eliciting an immune response is a SARS-CoV-2 antigen that is a Spike protein in order to develop a composition/vaccine that would reasonably be expected to be effective at producing an immune response against SARS-CoV-2, as suggested by Zhang, Babb, and Lei.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
In the instant case, it is noted that:
(1) The reference application claims liposome compositions that comprise: (i) an antigen, (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, and TLR agonist structures. Fox discloses stable liposome compositions capable of use in humans to elicit immune responses, wherein said liposome compositions comprise: (i) an antigen (e.g., viral antigens), (ii) two or more TLR agonists, and (iii) liposomes comprising a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid where said liposomes have the instant claimed properties regarding PEG weight, specific lipid compositions (e.g., molar percentages/ratios), liposome size, polydispersity index, thermostability, TLR agonist structures, and lyophilized products, wherein said liposome compositions are identified as being advantageous in the delivery of agents to produce an immune response.
(2) Zhang identifies a need to develop effective agents (e.g., vaccines) against SARS-CoV-2, and identifies that the Spike protein of SARS-CoV-2 is the most promising antigen in SARS-CoV-2 vaccine research and more specifically indicates the RBD domain is a commonly used antigen.
(3) Babb discloses neutralizing antibodies that specifically bind to SARS-CoV-2 Spike protein useful in preventative and therapeutic approaches wherein Babb further characterizes the specific epitopes that said antibodies bind; more specifically Babb identifies antigenic epitopes within the RBD of the SARS-CoV-2 Spike protein that are specifically bound by the antibodies wherein said antigenic epitopes are comprised within instant SEQ ID NO: 3.
(4) Lei discloses that using the SARS-CoV-2 S-RBD antigen with liposomal adjuvants, in the context of vaccination, specifically increased RBD-induced humoral immunity and also enhanced cellular immune response.
Thus, to one of ordinary skill in the art, it would have been obvious to try and modify the liposome composition/liposomes of the reference application such that the liposome was comprised within a pharmaceutical composition, such as those taught by Fox, capable of eliciting immune responses and wherein the antigen used is a SARS-CoV-2 antigen (e.g., Spike protein and/or antigenic fragment thereof), as suggested by Zhang, Babb, and Lei, wherein said liposome composition would reasonably be expected to be capable of eliciting an immune response against said SARS-CoV-2 antigen, as suggested by Fox, Zhang, Babb, and Lei, such that the liposome composition would be an effective approach to SARS-CoV-2 vaccination and preventing infection.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-24 are pending. Claims 1-24 are rejected. No claims are allowed.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642
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