DETAILED ACTION
Disposition of Claims
Claims 1-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, and 64-69 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20250295755A1, Published 09/25/2025.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/19/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of the use of implied phraseology (e.g. “Disclosed herein…” and “The disclosure also includes…”). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See ¶[0477] “https://www.european-virus-archive.com/virus/sars-cov-2-strain-slovakiask-bmc52020”.
Claim Objections
Claims 1 and 67 are objected to because of the following informalities: both claims comprise the limitation of “a lipid reconstructed plant messenger packs (LPMPs)” which uses a singular article (“a”) but then uses a plural noun (“packs”). To place the claim in better form, it is suggested that the recitation of “a” be deleted from before “lipid reconstructed plant messenger packs (LPMPs)”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: the definition of “mRNA” is not provided. It is requested that the first recitation of an abbreviation in a claim set be preceded by its non-abbreviated form (e.g. “…wherein the polynucleotide is messenger ribonucleic acid (mRNA).”.
Appropriate correction is required.
Claim 11 is objected to because of the following informalities: the definition of “SARS” is not provided. It is requested that the first recitation of an abbreviation in a claim set be preceded by its non-abbreviated form (e.g. “…wherein the antigenic polypeptide is a severe acute respiratory syndrome (SARS) virus...”).
Appropriate correction is required.
Claim 65 is objected to because of the following informalities: the definition of “HIV” is not provided, and further, it is followed by “virus”, wherein the claim now recites “…and an human immunodeficiency virus virus.”. It is requested that the first recitation of an abbreviation in a claim set be preceded by its non-abbreviated form (e.g. “…a hepatitis virus, and a human immunodeficiency virus (HIV).”). Further, to place the claim in better form, it is suggested claim 65 clearly further limit the virus of claim 64 (e.g. “…wherein the virus is selected from the group consisting of an influenza virus, a coronavirus, a mosquito-borne virus, a hepatitis virus, and a human immunodeficiency virus (HIV).”)
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 67 and dependent claims 2-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, 64-66, and 68-69 thereof 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 composition comprising an ionizable lipid within lipid reconstructed plant messenger packs (LPMPs), wherein the ionizable lipid must have at least two or more of the following characteristics:
(i) at least 2 ionizable amines;
(ii) at least 3 lipid tails, wherein each of the lipid tails is at least 6 carbon atoms in length;
(iii) a pKa of about 4.5 to about 7.5;
(iv) an ionizable amine and a heteroorganic group separated by a chain of at least two atoms; and
(v) an N:P ratio of at least 10.
However, the “N:P ratio” listed in item (v) is not a characteristic of a lipid, it is an abbreviation for a “Nitrogen to Phosphate Ratio” that is the molar ratio of positively charged amine groups (N) in the ionizable lipid to the negatively charged phosphate groups (P) in the nucleic acid cargo. The claimed characteristic is therefore unclear as to how it would apply solely to the ionizable lipid, as the N:P ratio is normally calculated as (moles of protonable nitrogen)/(moles of nucleic acid phosphates).
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claims 1 and 67 are rejected on the grounds of being indefinite. Claims 2-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, 64-66, and 68-69 are also rejected since they depend from claim(s) 1 or 67, but do not remedy these deficiencies of claim(s) 1 or 67.
Claim 1 and dependent claims 2-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, 64-66, and 68-69 thereof 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 the inclusion of “natural lipids” within the LPMPs. However, the metes and bounds of what are, and what are not, considered “natural lipids” have not been made clear in the claim or in the specification. The specification causes further confusion because it notes that “sterols” are listed as a separate component apart from “natural lipids”, yet sterols, such as cholesterol, are naturally-occurring lipids, and plants comprise sterols (e.g. phytosterols such as beta-sitosterol.) The claim nor the specification defines the “natural lipids” as only being from specific sources, and under the broadest reasonable interpretation, cholesterol and other naturally occurring sterols could also be considered “natural lipids”. Therefore, the metes and bounds of the claim are unclear.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claim 1 is rejected on the grounds of being indefinite. Claims 2-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, 64-66, and 68-69 are also rejected since they depend from claim 1, but do not remedy these deficiencies of claim 1.
Claims 1, 4, 34, 38, 40, 45, and 67 and dependent claims 2-3, 6, 8-9, 11-12, 48, 51-52, 64-66, and 68-69 thereof 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.
Claims 1, 4, 34, 38, 40, 45, and 67 use the term “about”. The term “about” in these claims is a relative term which renders the claims indefinite. The term “about” is not defined by the claim, 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.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claims 1, 4, 34, 38, 40, 45, and 67 are rejected on the grounds of being indefinite. Claims 2-3, 6, 8-9, 11-12, 48, 51-52, 64-66, and 68-69 are also rejected since they depend from claim(s) 1, 4, 34, 38, 40, 45, and 67, but do not remedy these deficiencies of claim(s) 1, 4, 34, 38, 40, 45, and 67.
Claim 2 is 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 2 notes that the natural lipids are extracted from “lemon or algae”. The “natural lipids” as recited in claim 1 are formulated within a lipid reconstructed plant messenger packs (LPMPs) [emphasis added] comprising natural lipids and an ionizable lipid, and the specification at ¶[0088] notes the LPMP has a lipid “derived from”(e.g. enriched, isolated, or purified from) a plant source. [emphasis added] “Algae” are not plants; while algae share the ability to photosynthesize, algae are classified as protists. Unlike true plants, they lack true roots, stems, leaves, and a complex vascular system. Therefore, it is unclear if the “algae” are used to produce or express the “true” plant-based lipids, or if the Applicant is attempting to redefine that “algae” are plants. As set forth supra with the rejection regarding “natural lipids”, this creates further confusion as to what is, and what is not, within the metes and bounds of the claimed invention, especially with respect to claim 2.
For at least these reasons, the metes and bounds of claim 2 are unclear.
Claim 6 is 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 6 comprises a list of ionizable lipids. Claim 6 contains the lipid “ALC-315”, and it is unclear if this refers to “ALC-0315”, the ionizable lipid used in COMIRNATY® vaccine, or if it refers to the lipid with the trademark/trade name ALC-315™ (lipid trademarked by Acuitas). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an ionizable lipid and, accordingly, the identification/description is indefinite.
Additionally, as the actual structures/chemical symbols of all the lipids are not provided, and the description of each lipid is recited generically in the specification, it is unclear if said lipids satisfy two or more of the criterion listed in independent claim 1. “EPC” appears to be a fixed cationic lipid (ethylphosphatidylcholine) rather than an ionizable lipid, but the structure does not appear to have been provided for to be clear. Likewise, structures for MD1 (cKK-E12), OF2, EPC, ZA3-Ep10, TT3, LP01, 5A2-SC8, Lipid 5, SM-102 (Lipid H), and ALC-315 are not clearly identified in the specification or the claim by clear chemical structures or molecular formulae. While chemical structures are provided for at ¶[0036][0165][0170-0250] for lipids, these chemical structures do not appear to be labeled as any of these lipid in instant claim 6. C12-200 appears to satisfy (i), (ii), and (iv).
For at least these reasons, the metes and bounds of instant claim 6 are unclear.
Claims 9 and 11 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.
Claims 9 and 11 state that the “antigenic polypeptide” is a coronavirus or a SARS virus. A polypeptide is not a virus. It is unclear if the intent was to claim an antigenic polypeptide derived from the recited virus, or is a specific peptide, such as the spike protein from SARS-CoV-2 as recited in claim 12.
For at least these reasons, claims 9 and 11 are rejected on the grounds of being indefinite.
Claim 12 is 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 12 is drawn to the nucleic acid vaccine of claim 11, wherein the antigenic polypeptide is a SARS-CoV-2 spike protein or a SARS-CoV-2 spike glycoprotein. However, the spike protein of SARS CoV-2 is a glycoprotein, so it is unclear if the claim meant to either limit the spike protein to being from SARS-CoV or SARS-CoV 2, or if the claim meant to identify a different glycoprotein of SARS-CoV 2 (e.g. both the spike (S) and membrane (M) proteins are glycoproteins, with some evidence that the ORF3a protein may be a glycoprotein.)
As the metes and bounds of the claim are unclear, claim 12 is rejected on the grounds of being indefinite.
Claim 38 is 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 38 directly depends upon claim 1, but recites “the sterol” and “the PEG-lipid conjugate”, which are not recited in claim 1. One suggestion is to have claim 38 depend upon claim 3, which provides proper antecedence for these limitations.
For at least these reasons, claim 38 is rejected on the grounds of being indefinite.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
“Heteroorganic group” is interpreted as any functional group that contains both a carbon and any other atom (e.g. any other atom aside from carbon or hydrogen).
Claim 1 is drawn to a nucleic acid vaccine, comprising:
one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent that causes an infectious disease, disorder, or condition, formulated within lipid reconstructed plant messenger packs (LPMPs) comprising natural lipids and an ionizable lipid, wherein the ionizable lipid has two or more of the characteristics listed below:
(i) at least 2 ionizable amines;
(ii) at least 3 lipid tails, wherein each of the lipid tails is at least 6 carbon atoms in length;
(iii) a pKa of about 4.5 to about 7.5;
(iv) an ionizable amine and a heteroorganic group separated by a chain of at least two atoms; and
(v) an N:P ratio of at least 10.
Further limitations on the nucleic acid vaccine of claim 1 are wherein the natural lipids are extracted from lemon or algae (claim 2); wherein the LPMPs further comprise a sterol and a polyethylene glycol (PEG)-lipid conjugate (claim 3), wherein the LPMPs comprise ionizable lipid:natural lipids:sterol:PEG-lipid at a molar ratio of about 35:50:12.5:2.5 or about 35:20:42.5:2.5 (claim 4); wherein the ionizable lipid is selected from the group consisting of 1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl) (2- hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol) (C 12-200), MD 1 (cKK-E12), OF2, EPC, ZA3-Ep10, TT3, LPO1, 5A2-SC8, Lipid 5, SM-102 (Lipid H), and ALC- 315 (claim 6); wherein the polynucleotide is messenger ribonucleic acid (mRNA)(claim 8); wherein the antigenic polypeptide is a polypeptide, or a fragment or subunit thereof, from a coronavirus (CoV)(claim 9); wherein the antigenic polypeptide is a polypeptide, or a fragment or subunit thereof, from a severe acute respiratory syndrome (SARS) coronavirus (CoV)(claim 11), wherein the antigenic polypeptide is a SARS-CoV-2 spike protein or a SARS-CoV-2 spike glycoprotein (claim 12); wherein the LPMP has a size of less than about 100 nm (claim 34); wherein the LPMP comprises: about 20 mol% to about 50 mol% of the ionizable lipid, about 20 mol% to about 60 mol% of the natural lipids, about 7 mol% to about 20 mol% of the sterol, and about 0.5 mol% to about 3 mol% of the polyethylene glycol (PEG)-lipid conjugate (claim 38); wherein the nucleic acid vaccine has a total lipid:polynucleotide weight ratio of about 50:1 to about 10:1 (claim 40); further comprising a HEPES or TRIS buffer at a pH of about 7.0 to about 8.5 (claim 45); further comprising one or more cryoprotectants (claim 48); wherein the nucleic acid vaccine is a lyophilized composition (claim 51), wherein the lyophilized nucleic acid vaccine comprises one or more lyoprotectants (claim 52); wherein the infectious agent is a virus (claim 64), wherein the virus is selected from the group consisting of an influenza virus, a coronavirus, a mosquito-borne virus, a hepatitis virus, and a human immunodeficiency virus (HIV)(claim 65), and wherein the virus is selected from the group consisting of a respiratory syncytial virus, a rhinovirus, an adenovirus, and a parainfluenza virus (claim 66).
Claim 67 is drawn to a method for making a nucleic acid vaccine, comprising:
reconstituting a film comprising purified PMP lipids in the presence of an ionizable lipid to produce lipid reconstructed plant messenger packs (LPMP) comprising the ionizable lipid, wherein the ionizable lipid has two or more of the characteristics listed below:
(i) at least 2 ionizable amines;
(ii) at least 3 lipid tails, wherein each of the lipid tails is at least 6 carbon atoms in length;
(iii) a pKa of about 4.5 to about 7.5;
(iv) an ionizable amine and a heteroorganic group separated by a chain of at least two atoms; and
(v) an N:P ratio of at least 10, and
loading into the LPMPs with one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent that causes an infectious disease, disorder, or condition.
Claim 68 is drawn to a method of preventing or reducing the transmission of an infectious disease, disorder, or condition, comprising: administering to a subject the nucleic acid vaccine of claim 1, thereby preventing or reducing the transmission of an infectious disease, disorder, or condition.
Further limitations on the method of claim 68 are wherein the method prevents or reduces the transmission of the infectious agent from a vaccinated host to an unvaccinated host or from a vaccinated host to a vaccinated host (claim 69).
Claim Rejections - 35 USC § 112(a); First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, and 64-69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for recLemon and recAlgae LPMP/SARS-CoV-2 S mRNA formulations containing C12-200, cholesterol, and DMPE-PEG-2000, does not reasonably provide enablement for the full scope of any LPMP with any natural lipids, any ionizable lipid with the claimed characteristics, and any polynucleotides encoding antigens from any infectious agents. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors to be considered include: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The factors are considered as a whole in determining whether any necessary experimentation would have been undue.
Nature of the invention and breadth of the claims. The claimed invention is directed to LPMP nucleic-acid vaccines comprising one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent, wherein the polynucleotides are formulated within LPMPs comprising natural lipids and an ionizable lipid having two or more of the claimed characteristics.
As set forth supra in the 35 USC 112b rejection, “algae” is actually a class of photosynthetic organisms classified as protists. There are over 50,000 documented species of living algae, broadly categorized into 14 phyla based on their pigmentation, cell structure, and evolutionary history. While highly diverse, they are most commonly divided into major groups, ranging from microscopic single-celled phytoplankton to massive multicellular seaweeds.
“Lemon” is a fruit in the citrus family, with over 30 different varieties known. They are generally categorized into "true" lemons (like Eureka and Lisbon) and "rough" or hybrid lemons (like Meyer and Ponderosa). While lemons are effectively fat-free (containing less than 0.5 g of fat per 100 g), their pulp, peel, and seeds still contain trace amounts of various lipids, primarily consisting of fatty acids (saturated, monounsaturated, and polyunsaturated fatty acids, namely linoleic acid, palmitic acid, oleic acid, and stearic acid) and functional lipids (such as phytosterols, including β-sitosterol, and lipid-soluble bioactives.)
The specification describes recLemon and recAlgae LPMP/SARS CoV-2 S mRNA formulations. In Example 2 (starting at ¶[0475]), the recLemon and recAlgae formulations tested contains the ionizable lipid C12-200, naturally derived lemon/algae lipids, cholesterol, and DMPE-PEG-2k, along with a SARS CoV-2 S mRNA sequence (¶[0487]). The lipid nanoparticles comprised the components (C12-200: lemon lipid:cholesterol:DMPE-PEG-2k) at a ratio of 35:50:12.5:2.5 molar ratio (¶[0489]), the algae-based LPMP formulation was prepared to result in ionizable lipid:natural lipids:sterol:PEG-lipid (C12-200:algae lipid:cholesterol (14:0): DMPE-PEG2k) at a molar ratio of 35:20:42.5:2.5 (¶[0490]). The SARS CoV-2 S protein mRNA that was used appears to be that defined in Table 1, namely a mRNA with a 5’ cap, 5’ UTR, native signal peptide, codon-optimized sequence encoding full-length SARS-CoV-2 spike (S) glycoprotein containing mutations K986P and V987P to ensure the S glycoprotein remains in an antigenically optimal pre-fusion conformation, 3’ UTR, and a 3’ polyA tail (Table 1 at ¶[0480]).
However, the claims are not limited to the disclosed embodiments. The claims also encompass any nucleic acid in the composition encoding any one or more antigenic polypeptides encoded by said nucleic acid from any infectious agent which causes any infectious disease, which is not limited to SARS-CoV-2, and extends to any virus, bacteria, parasite, or other pathogen. The claims additionally encompass LPMP vaccines using natural lipids from other sources, other ionizable lipids which fall within the structural characteristics claimed, different LPMP formulation ratios, additional reagents (e.g. stabilizers, buffers, adjuvants, etc.) The claimed scope therefore extends beyond the embodiments described in the specification.
State of the prior art and predictability of the art. At the time the application was filed, LPMP technology was known in the art, but it was still very much context-dependent. Van Rooijen (WO2021041301A1; CITED IN IDS) teaches that plant messenger packs (PMPs) may be “lipid reconstituted PMPs (LPMPs)” and that LPMPs may comprise an “exogenous cationic lipid” (p. 1; p. 7, ¶6). Van Rooijen exemplifies grapefruit or lemon LPMPs modified with DOTAP or DC-cholesterol and loaded with short RNA cargo for plant cell delivery (p. 7, ¶6; Example 5 starting at p. 56). Van Rooijen does not establish that any plant source can be used for the plant-based lipid, any mRNA encoding any antigen, and any ionizable lipid satisfying the claimed characteristics would provide an operable vaccine formulation in a mammalian subject.
Patel et. al. (Patel S, et. al. Nat Commun. 2020 Feb 20;11(1):983.) further shows that lipid nanoparticle performance depended on lipid structure. Patel reports that “C-24 alkyl phytosterols” enhanced gene transfection, but also reports that differences in sterol tail length, sterol-ring flexibility, and hydroxyl-group polarity affected performance. Patel is useful in that it teaches both sides of the coin: plant-derived lipid components could improve mRNA delivery, but small structural differences in the lipid components changed nanoparticle morphology and transfection capabilities.
Stewart-Jones (WO2021159040A2) teaches SARS-CoV-2 mRNA-LNP vaccines. Stewart-Jones teaches that “the mRNA is formulated in a lipid nanoparticle” and describes LNPs containing an ionizable cationic lipid, a neutral lipid, a sterol, and a PEG-modified lipid. Stewart-Jones shows that the antigen and formulation are linked to a particular immune response, including neutralizing antibody responses against SARS CoV-2, and that the S protein needed to be mutated to be maintained in a prefusion stabilized form for maximum immunogenicity, but also that synergy could be achieved with the inclusion of two different domains of the same protein presented as two separate antigens in the LNP mixture.
Suharta et. al. (Suharta S, et. al. J Food Sci. 2021 Jul;86(7):2838-2850. Epub 2021 Jun 20.) further indicates that plant-derived exosome-like nanoparticles were not a predictable plug-and-play delivery platform at the time of filing. Suharta reports that macrophage and other cells absorb plant-derived exosome-like nanoparticles (PDENs) “in a manner regulated by the membrane lipid and protein profile and the intactness of the PDENs lipid bilayer.” Suharta also reports that PDENs could be extracted by ultracentrifugation, immunoaffinity, size-based isolation, and precipitation, though “each method has its pros and cons” and that the potency of the PDENs “remains a question” because PDENs are “sensitive to storage and processing condition” and require costly extraction. Suharta therefore supports that plant-derived vesicle/lipid nanoparticle performance depended on lipid/protein profile, bilayer integrity, extraction method, and processing conditions, rather than being predictable across plant sources and formulations.
The art was not sufficiently predictable to support extrapolation from the narrowly disclosed algae and lemon based LPMPs with the specific additional lipids and specific SARS CoV-2 mRNA to the broadly claimed LPMPs with any natural based lipids, any of the ionizable lipids at any ratio and delivering any nucleic acid encoding any pathogenic antigen. Accordingly, the results obtained using the recLemon and recAlgae based SARS CoV-2 mRNA compositions would not have reasonably established that the broader claimed scope could be practiced without further experimentation.
Level of skill in the art. One skilled in the art would have been familiar with lipid extraction and nanoparticle formulation, as well as nucleic acid (including mRNA) design, synthesis, and isolation. It was known in the art at the time of filing how to perform encapsulation assays with LNPs and nucleic acids, and perform immunogenicity assays as well as viral challenge studies. However, the existence of these known methods for preparing and testing candidate embodiments does not establish that one skilled in the art would have known, without further experimentation, which additional natural lipids, ionizable lipids, sterol-based lipids, and PEGylated lipids in which LPMPs along with which nucleic acids encoding which antigens from which pathogens would satisfy the claimed limitations.
Working examples. The specification provides working examples directed to recLemon and recAlgae LPMP/SARS-CoV-2 S mRNA formulations. The specification reports mouse and hamster immunogenicity studies, SARS CoV-2 challenge data in hamsters, and a hamster transmission model using the LPMP/SARS-CoV-2 formulation (Examples 3-8 starting at ¶[0494]).
The specification does not provide working examples directed to any other LPMP vaccine formulations with any other natural lipids, any other ionizable lipids that structurally meet the claimed limitations, any other sterols, any other PEGylated lipids, or any other nucleic acids encoding any other antigens, such as adenovirus, influenza, HIV, parainfluenza, or respiratory syncytial virus antigens. It is not clear as to what species of lemon and/or algae was used to generate the lipids from each source, nor is the exact amount or type of lipid within the extracts present in the specification. The art shows that for lemon extracts, the physicochemical properties and the bioactive compounds of the peel, such as the essential oil, are strictly dependent on the genotype and cultivar (see e.g. Modica G, et. al. Food Biosci. Vol.59. June 2024, 103881.) The disclosed examples therefore do not establish enablement across the full scope of the claims.
Guidance in the specification. The specification provides guidance regarding preparation of the recLemon and recAlgae LPMP/SARS CoV-2 S mRNA formulations. However, the specification does not provide sufficient guidance regarding the type of Lemon and/or Algae used to generate the lipid extracts, the types of lipids present in said extracts, the different ionizable lipids aside from C12-200 which may be used and in what molar ratios, N:P ratios, or other LNP-related parameters, such as particle size and encapsulation efficiency. The specification provides a large list of possible infectious agents, but only tests the specific spike protein mRNA structure from SARS CoV-2. In particular, the specification does not explain which formulation changes may be made while still obtaining a vaccine that expresses antigen, induces a protective immune response, and prevents or reduces transmission for infectious agents beyond SARS CoV-2. The specification also fails to explain how the recLemon and recAlgae SARS-CoV-2 results should be extrapolated to the broader virus or pathogen categories claimed.
Quantity of experimentation necessary. To practice the full scope of the claims, one skilled in the art would need to select additional Algae lipid extracts, lemon lipid extracts, or other plant-derived lipid sources, prepare additional LPMP formulations with ionizable lipids that fit into the structural parameters of the claim, load additional nucleic acids (e.g. other forms of DNA and RNA, such as plasmids or vectors) encoding other antigens from other pathogens, optimize these formulation ratios, measure how well the nucleic acid is encapsulated and/or expressed, determine the immune response that is elicited in which species, and test for protection and/or transmission in the appropriate in vivo models. Such experimentation would not merely involve the routine application of known methods to embodiments reasonably expected to work. Instead, one skilled in the art would need to prepare and test additional embodiments to determine whether they satisfy the claimed limitations encompassed by the claimed vaccine formulations and the claimed functional results in the claimed methods. Although the individual methods used to prepare and test candidate embodiments may have been known in the art, the relevant inquiry is not whether one skilled in the art could perform the required assays. The relevant inquiry is whether the specification provides sufficient guidance to identify and practice the embodiments falling within the full scope of the claims without undue experimentation. Here, one skilled in the art would need to prepare and test additional LPMP vaccine formulations to determine which embodiments satisfy the claimed vaccine and transmission-reduction limitations.
Amgen. The Supreme Court has explained that a specification need not describe with particularity how to make and use every embodiment within a claimed class. However, the disclosure must enable one skilled in the art to make and use the full scope of the claimed invention. A reasonable amount of experimentation may be permissible depending on the nature of the invention and the underlying art. Amgen Inc. v. Sanofi, 598 U.S. 594, 610-13 (2023).
In the instantly claimed invention, the specification describes recLemon and recAlgae LPMP/SARS CoV-2 S mRNA formulations, but it is unclear as to the exact lipids encompassed by the lemon and algae extract, and the claims also encompass additional LPMP vaccines using extracts from any lemon or any algae source, any natural lipid source, additional ionizable lipids (which fit within the claimed structural parameters), and antigen-encoding polynucleotides from a broad genus of pathogenic sources. The specification does not identify a general quality or provide sufficient guidance that would allow one skilled in the art to practice that broader scope without undue experimentation.
Conclusion. For the reasons discussed above, the specification does not enable one skilled in the art to make or use the full scope of the invention recited in the claims without undue experimentation.
Claims 1-4, 6, 8-9, 11-12, 34, 38, 40, 45, 48, 51-52, and 64-69 are rejected under 35 U.S.C. 112(a), or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement, the specification must reasonably convey to one skilled in the relevant art that the inventor had possession of the claimed invention as of the filing date. Possession may be shown by a description of the complete structure of the claimed invention, a representative number of species falling within the scope of a claimed genus, or relevant identifying characteristics sufficient to show that the inventor had possession of the claimed subject matter.
The claims are directed to LPMP nucleic-acid vaccines comprising one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent, wherein the polynucleotides are formulated within LPMPs comprising natural lipids and an ionizable lipid having two or more of the claimed characteristics. The claims also encompass methods of making said compositions, as well as methods of using said vaccine compositions for preventing or reducing transmission of an infectious disease, disorder, or condition.
The specification describes recLemon and recAlgae LPMP/SARS CoV-2 S mRNA formulations. In Example 2 (starting at ¶[0475]), the recLemon and recAlgae formulations tested contains the ionizable lipid C12-200, naturally derived lemon/algae lipids, cholesterol, and DMPE-PEG-2k, along with a SARS CoV-2 S mRNA sequence (¶[0487]). The lipid nanoparticles comprised the components (C12-200: lemon lipid:cholesterol:DMPE-PEG-2k) at a ratio of 35:50:12.5:2.5 molar ratio (¶[0489]), the algae-based LPMP formulation was prepared to result in ionizable lipid:natural lipids:sterol:PEG-lipid (C12-200:algae lipid:cholesterol (14:0): DMPE-PEG2k) at a molar ratio of 35:20:42.5:2.5 (¶[0490]). The SARS CoV-2 S protein mRNA that was used appears to be that defined in Table 1, namely a mRNA with a 5’ cap, 5’ UTR, native signal peptide, codon-optimized sequence encoding full-length SARS-CoV-2 spike (S) glycoprotein containing mutations K986P and V987P to ensure the S glycoprotein remains in an antigenically optimal pre-fusion conformation, 3’ UTR, and a 3’ polyA tail (Table 1 at ¶[0480]). The specification also describes mouse and hamster studies with the vaccine formulations, especially hamster challenge and transmission studies of SARS CoV-2.
However, the scope of the claims is not limited to the recLemon/ and recAlgae/SARS-CoV-2 S mRNA embodiments described in the specification. The claims broadly encompass LPMP vaccines using additional plant-derived natural lipid compositions. The specification refers to “lemon lipid”, “algae lipid”, “natural lipids extracted from lemon”, and “natural lipids extracted from algae”, but does not identify the lemon cultivar, lemon tissue or part, algae species, algae group, culture/harvest conditions, lipid profile of the obtained extracts, or any other compositional characteristics of the extracted materials. The disclosure therefore does not describe what structural or compositional features of this element are required for the lemon or algae lipids. Claim 1 has an even broader scope, as it is drawn to “natural lipids”, and the specification fails to describe a number of natural lipid components across the scope and also fails to identify specific structural features common to these “natural lipids” which would allow a skilled artisan to identify which natural lipids fall within the claimed LPMP genus.
Additionally, the claims encompass LPMP constructs that differ in the lipid species in the ionizable lipid components, the sterol components, and the PEGylated lipid components, as well as the polynucleotide format and the identity of the one or more antigens said polynucleotide can encode. The claims encompass more than SARS CoV-2 infections and reasonably encompass any disease, disorder, or infection caused by any infectious agent. The specification does not describe a sufficient number of species representative of the claimed scope. The specification also does not describe structural features common to the claimed genera (e.g. natural lipids, polynucleotide, infectious agent, etc.) which would allow one skilled in the art to recognize which additional species fall within the scope of the claimed invention. Instead, one skilled in the art would be required to select additional natural lipids, ionizable lipids which fit within at least two parameters of claim 1, PEGylated lipids, sterols, polynucleotides, and infectious agents not described in the specification and determine whether those additional embodiments satisfy the recited limitations.
The specification describes recLemon and recAlgae LPMP/SARS-CoV-2 S mRNA compositions. However, the claims are not limited to those constructs. The claims also encompass constructs that differ in the natural-lipid source, the actual lipid species present in the natural-lipid fraction, the ionizable lipid, the sterol, the PEGylated lipid, the polynucleotide format, the encoded antigen(s), and the infectious disease/agent. The specification does not describe representative examples across that scope or identify structural features sufficient to show possession of the broader group of constructs.
The specification describes SARS-CoV-2 S mRNA constructs, namely codon-optimized mRNA with K986P and V987P prefusion stabilizing mutations, and the mRNA comprises additional structural components, such as 5’ cap, 3’ polyA tail, and 5’/3’ UTRs. However, the claims also encompass additional RNA and DNA species encoding antigens from different viruses, viral strains, and infectious agents. The specification does not describe representative antigen-encoding sequences across the full claimed scope, nor does it identify which antigen structures are suitable for the infectious agent or recited viruses. The general statement that the antigen may be derived from an infectious agent does not demonstrate possession of the broader claimed group of infectious-agent antigen vaccines.
The specification describes vaccination studies using recLemon and recAlgae LPMP/SARS CoV-2 S mRNA formulations in mice and hamsters, including SARS CoV-2 challenge and transmission studies in hamsters. However, the claimed methods broadly encompass methods of preventing or reducing transmission of any infectious disease, disorder, or condition using the full scope of the vaccine of claim 1. The specification does not describe representative transmission-reduction methods across the breadth of the claimed LPMP formulations or infectious agents. The disclosure of the results obtained with the SARS-CoV-2 S mRNA LPMP formulations does not reasonably convey possession of methods using the broader group of LPMP vaccines and infectious agents encompassed by said claims.
Accordingly, the disclosure does not reasonably convey to one skilled in the art that the inventor had possession of the full scope of the subject matter recited the claims at the time the application was filed.
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 1-3, 6, 8-9, 11-12, 34, 64-65, and 67-69 are rejected under 35 U.S.C. 103 as being unpatentable over van Rooijen et. al. (WO2020041782A1, Pub. 02/27/2020, hereafter “van Rooijen”) in view of Stewart-Jones (WO2021159040A2, Priority 02/07/2020; hereafter “Stewart-Jones”.)
The Prior Art
Van Rooijen teaches plant messenger packs (PMPs) and lipid reconstituted PMPs (LPMPs), wherein the lipids may be extracted from a plant extracellular vesicle (EV)(entire document; see pp. 14-15, figure legends for Figs. 9-15; p. 18, ¶3; p. 75, ¶2). Van Rooijen teaches preparing LPMPs from lemon PMPs and modifying the LPMPs with cationic or ionizable lipids (Table 1; p. 11, ¶2; p. 75, ¶2; p. 76, ¶2; p. 77, ¶1; p. 78, ¶1-2; p. 79, ¶3; instant claim 2). Van Rooijen further teaches LPMPs comprising DOTAP or DC-cholesterol and teaches loading negatively charged RNA cargo into the LPMPs (p, 7, ¶6; p. 15, ¶2-4; p. 74, ¶4; p. 79, ¶2; Figs. 11, 13.) Van Rooijen teaches that modified RNAs encoding polypeptides can be delivered by the LPMPs/PMPs (p. 41, ¶4), and that said modified RNAs can include those which encode viral material (p. 42; ¶5). Van Rooijen teaches generation of LPMPs of average size of less than 100 nm (p. 13, ¶10; p. 72, ¶1; instant claim 34).
While Van Rooijen teaches the majority of structural components of the claimed composition, Van Rooijen does not expressly teach a nucleic acid vaccine comprising mRNA encoding a SARS-CoV-2 spike (S) antigen, and while Van Rooijen teaches ionizable lipids, Van Rooijen does not expressly teach ionizable lipids with the structural limitations of instant claim 1 or 6, such as “Compound 1”/SM-102/ 9-Heptadecanyl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate. However, Stewart-Jones teaches mRNA-LNP vaccine compositions which encode SARS-CoV-2 S protein antigens, such as receptor binding domain (RBD) and N-terminal domain (NTD) antigens, wherein the LNPs include SM-102 as the ionizable cationic lipid, cholesterol, a PEGylated lipid, and a neutral lipid (entire document; see abstract; reference claims 1-3, 65-66, 69-80; instant claims 3, 6, 8-9, 11-12, 64-65.) Stewart-Jones teaches that the mRNA-LNP SARS-CoV-2 S compositions may be used in methods to induce a neutralizing antibody response against SARS-CoV-2 and to induce a T-cell response against SARS-CoV-2, especially for prevention or treatment of infection in humans and other mammals, wherein the vaccine can protect people from infection by the live and spreading SARS-CoV-2 virus (reference claims 148-153; p. 2, ¶1; p. 117, ¶4 to p. 118, ¶3; p. 129, ¶2; Example 1 at p. 142.)
It would have been obvious to one of ordinary skill in the art at the time of filing to load the LPMP carrier of Van Rooijen with the SARS-CoV-2 antigen encoding mRNA taught by Stewart-Jones and to use SM-102 as the ionizable lipid in the LPMP formulation. Van Rooijen teaches that LPMPs can be modified with added cationic/ionizable lipids to improve surface charge, cargo loading capacity, and cellular uptake, and further teaches RNA cargo loading into LPMPs. Stewart-Jones teaches a known SARS-CoV-2 mRNA vaccine cargo and teaches lipid nanoparticle formulations comprising an ionizable cationic lipid (SM-102), sterol (cholesterol), neutral lipid, and a PEG-modified lipid for delivery of that mRNA vaccine cargo. One of ordinary skill in the art would have had reason to use Stewart-Jones’ SARS-CoV-2 antigen encoding mRNA and SM-102 in Van Rooijen’s LPMP system as Van Rooijen noted that such RNAs were known in the art and could be delivered in their LPMP systems, given that both sets of teachings concern lipid-based delivery of RNA cargo, and given that Stewart-Jones supplies a known vaccine mRNA payload and ionizable lipid for LNP mRNA delivery. This rejection is based on the specific combination of Van Rooijen’s LPMP/RNA carrier teachings with Stewart-Jones’ SARS-CoV-2 mRNA vaccine and SM-102 teachings. The rejection does not require a finding that every natural lipid extract, every lemon or algae source, or every infectious agent antigen would have been predictable across the full scope of the claims. The reasonable expectation of success is limited to using a known LPMP RNA carrier with a known SARS-CoV-2 mRNA vaccine cargo and a known ionizable lipid used in mRNA formulations. Therefore, the vaccine and methods of prophylactic and therapeutic use thereof to prevent or treat SARS-CoV-2 disease, spread, and transmission would be obvious given the teachings of Van Rooijen and Stewart-Jones, and the limitations of instant claims 1 and 67-69 would be obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to modify the LPMP/RNA compositions taught by Van Rooijen in order to include SARS-CoV-2 S antigen encoding mRNA and SM-102, thereby producing a nucleic acid vaccine comprising antigen-encoding mRNA formulated within LPMPs containing natural lipids and an ionizable lipid. One would have been motivated to do so, given the suggestion by Van Rooijen that LPMPs may be modified with ionizable/cationic lipids to improve cargo loading and cellular uptake. There would have been a reasonable expectation of success, given the knowledge that Van Rooijen teaches LPMP carrier suitable for RNA loading, and Stewart-Jones teaches a known SARS-CoV-2 mRNA vaccine cargo and a known ionizable cationic lipid (SM-102) used for lipid-based mRNA delivery. Thus, the claimed invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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 1-3, 6, 34, 38, and 67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-12, and 14 of U.S. Patent No. 12,409,137 in view of Van Rooijen. Both sets of claims are drawn to methods of making lipid plant messenger packs (LPMPs) through reconstituting a film comprising purified lipids derived from a plant source in the presence of a synthetic charged lipid. Both the instant claims and the reference claims note the lipid may be OF2 or C12-200. Both sets of claims note the LPMP may comprise a sterol and a PEG-lipid conjugate, both note that the LPMP would have lipids from a plant source in the same molar ratios. Both claim the LPMPs comprise a heterologous polynucleotide from an infectious agent, such as a virus, and that the composition may be formulated for delivery to an animal. While the instant claims do not explicitly note the sterol as being cholesterol and the PEGylated lipid as being C14-PEG2k, C18-PEG2k, or DMPE-PEG2k, these would be obvious species in light of the teachings of Van Rooijen, which teach that the sterol may be cholesterol, the PEGylated lipid as being C14-PEG2k, C18-PEG2k, or DMPE-PEG2k, and the size of the LPMP being less than 100 nm (see teachings of Van Rooijen detailed supra.) Van Rooijen teaches the plant lipids may be from lemon or algae.
Therefore, the instant claims and the ‘137 claims are not patentably distinct, especially in light of the teachings of Van Rooijen.
Claims 1-4, 8-9, 11-12, 34, 38, 64-65, and 67-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 8, 23-24, 27-28, 33-34, 38, 45, 91, 94-95, and 108 of copending Application No. 18/569,924 in view of Van Rooijen and Stewart-Jones. Both sets of claims are drawn to compositions and methods of making lipid plant messenger packs (LPMPs) through reconstituting a film comprising purified lipids derived from a plant source in the presence of a synthetic charged lipid. Both the instant claims and the reference claims note the lipid must be an ionizable lipid that has at least 2 ionizable amines and at least 3 lipid tails. Both sets of claims note the LPMP may comprise a sterol and a PEG-lipid conjugate, both note that the LPMP would have lipids in the same molar ratios. Both claim the LPMPs comprise a heterologous polynucleotide, such as mRNA, and that the composition may be formulated for delivery to an animal. While the instant claims do not explicitly note the sterol as being cholesterol and the PEGylated lipid as being C14-PEG2k, C18-PEG2k, or DMPE-PEG2k, these would be obvious species in light of the teachings of Van Rooijen, which teach that the sterol may be cholesterol, the PEGylated lipid as being C14-PEG2k, C18-PEG2k, or DMPE-PEG2k, and the size of the LPMP being less than 100 nm (see teachings of Van Rooijen detailed supra.) Van Rooijen teaches the plant lipids may be from lemon or algae. While the reference claims are drawn to delivery of mRNA, they do not explicitly state that such mRNA would encode viral antigens, such as SARS-CoV-2 S protein antigens; however, such a difference would be obvious given the teachings of Stewart-Jones (supra). The reference claims teach “increasing the fitness of an animal”, which the vaccination methods that decrease the incidence of infection or infection transmission of Stewart-Jones would be increasing the fitness of an animal. Therefore, the differences between the instant claims and the ‘924 claims are not patentably distinct in light of the teachings of Van Rooijen and Stewart-Jones.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 8-9, 11-12, 34, 38, 64-65, and 67-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 34-35, and 40-41 of copending Application No. 18/710,109 in view of Van Rooijen and Stewart-Jones. Both sets of claims are drawn to compositions comprising mRNA and charged lipids. Both the instant claims and the reference claims note the lipid must be an ionizable lipid that has at least 2 ionizable amines and at least 3 lipid tails, and the lipids of ‘109 are a species of the genus of lipids of the instant claims. While the ‘109 claims state that the lipids would be in compositions to encapsulate mRNA, the ‘109 claims are not explicitly drawn to LPMPs. However, these would be obvious in light of the teachings of Van Rooijen, which teach the LPMPs and the inclusion of the ionizable/cationic lipid with the PMPs, and the size of the LPMP being less than 100 nm (see teachings of Van Rooijen detailed supra.) Van Rooijen teaches the plant lipids within the LPMPs may be from lemon or algae. While the reference claims are drawn to delivery of mRNA, they do not explicitly state that such mRNA would encode viral antigens, such as SARS-CoV-2 S protein antigens; however, such a difference would be obvious given the teachings of Stewart-Jones (supra). The reference claims teach “increasing the fitness of an animal”, which the vaccination methods that decrease the incidence of infection or infection transmission of Stewart-Jones would be increasing the fitness of an animal. Therefore, the differences between the instant claims and the ‘924 claims are not patentably distinct in light of the teachings of Van Rooijen and Stewart-Jones.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 6, 8, 34, 38, 40, 45, 48, 51-52, 64, 67-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 33, 39, 41, 46, 49, 52, 66-67, 88-89 of copending Application No. 18/721,328 in view of Valiante et. al. (US20180318409A1.)
Both sets of claims are drawn to compositions comprising mRNA and ionizable lipids with the same structural characteristics in LPMPs. Both the instant claims and the reference claims note the lipid must be an ionizable lipid that has at least 2 ionizable amines and at least 3 lipid tails. Both claim the natural lipids in the LPMP are from lemon or algae. Both claim that the LPMPs further comprise sterol and a PEGylated lipid. Both claim the same LPMP lipid ratios, both claim the same ionizable lipids. Both claim that the LPMP is smaller than 200 nm. Both claim the same total lipid: polynucleotide weight ratios. Both claim the use of the same buffers, both claim the compositions may be lyophilized and comprise cryoprotectants. Both claim methods of delivering the compositions and inducing an immune response in a subject with said compositions. The claims recite the same LPMP/natural lipid/ionizable lipid delivery platform, and differ only in the identity of the encoded polypeptide cargo. Reference claim 1 recites the delivery of a “tumor antigen” or “signaling polypeptide”, while instant claim 1 recites an antigenic polypeptide from an infectious agent. To the extent reference claim 1 encompasses viral tumor antigens, or to the extent the art recognized antigen-encoding mRNA cargos for cancer and infectious-disease vaccination as interchangeable payloads in lipid-bases vaccine systems, the claimed subject matter is not patentably distinct. For instance, Valiante notes that cancer preventative vaccines and infectious agent vaccines are overlapping, as infectious agents such as human papillomavirus (HPV) can cause cancer (entire document; see abstract; ¶[0002]). Valiante teaches a mRNA-LNP platform for delivery of antigens to a subject in order to therapeutically treat or inhibit cancer and/or infectious agents. Therefore, the differences between the instant claims and the ‘328 claims are not patentably distinct in light of the teachings of Valiante.
This is a provisional nonstatutory double patenting rejection.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claim 1 is provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1 of copending Application No. 19/476,020 (reference application).
Both instant claim 1 and reference claim 1 are drawn to a nucleic acid vaccine, comprising: one or more polynucleotides encoding one or more antigenic polypeptides derived from an infectious agent that causes an infectious disease, disorder, or condition, formulated within a lipid reconstructed natural messenger packs (LNMPs) comprising natural lipids and an ionizable lipid, wherein the ionizable lipid has two or more of the characteristics listed below:(i) at least 2 ionizable amines;(ii) at least 3 lipid tails, wherein each of the lipid tails is at least 6 carbon atoms in length;(iii) a pKa of about 4.5 to about 7.5;(iv) an ionizable amine and a heteroorganic group separated by a chain of at least two atoms; and(v) an N:P ratio of at least 3.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and is listed below.
Kim J, et. al. Cell Mol Bioeng. 2020 May 26;13(5):463-474. Teaches plant-based LNPs for delivery of cargo to treat infectious agents in lungs. Not utilized as rejection would be redundant to those set forth supra.
Kalarikkal SP, et. al. Toxicol Appl Pharmacol. 2021 Mar 1;414:115425. Epub 2021 Jan 29. Teaches plant-based vesicles for delivery of nucleic acid cargo (miRNA) to target SARS-CoV-2. Not utilized as rejection would be redundant to those set forth supra.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
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