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 .
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.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the instant application includes nucleotide sequences, at least as of page 334, paragraph 0791, relevant text reproduced below.
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Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Examiner Note Regarding ST.26 vs. ST.25: The instant application was filed with the USPTO on 28 November 2023. This application claims priority to PCT/US2022/031383; however, this priority claim is as a continuation application. As such, the instant application is not a national phase of PCT/US2022/031383. As such, as best understood by the examiner, the relevant date for determination of whether ST.25 or ST.26 sequence rules applies is 28 November 2023. This is later than 1 July 2022. As such, the examiner understands that ST.26 sequence rules are applicable.
In support of this position, the examiner notes MPEP 2412, which states that
This section is applicable to all applications with a filing date, or, for national phase applications, an international filing date, on or after July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences as defined in 37 CFR 1.831(b).
As best understood by the examiner, for applications that are not national phase applications, such as the instant application, the filing date is the date at which the application was filed with the USPTO, not its priority date.
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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/194,498, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Specifically, the ‘498 provisional application fails to adequately support the following compounds, as recited in claim 1.
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As the ‘498 provisional application fails to adequately provide support for the above-indicated compounds, the examiner will examine the instant application with the understanding that the effective filing date is 27 May 2022.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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, 6-8, 14-15, 18-19, 22, 24-28, 32, 36, 42-43, and 46 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.
Instant claim 1 recites the following:
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This renders claim 1 indefinite for the following reasons. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." See MPEP 2173.05(s). The instant case does not appear to be an exceptional circumstance where there is no practical way to set forth the claim without incorporation by reference of the lipids from the indicated publications. As such, the instant claims are understood to be indefinite for the reasons set forth above.
This issue also applies to claim 8, which recites “Table 1.” The reference to table 1 is understood to be indefinite for the reasons set forth in MPE 2173.05(s).
This rejection does not apply to claim 2, which limits the required compound to Compound 1 or Compound 2.
For the purposes of examination under prior art, the examiner will search for compounds 1 and/or 2, and the examiner will also review the publications specifically cited in claim 1 to determine whether these are prior art. The examiner notes that if applicant were to amend claim 1 to include additional cationic lipids other than compounds 1 or 2, then this would be understood to necessitate a new search that might require the examiner to write a new ground of rejection necessitated by amendment. Also, for the purposes of examination under prior art, claim 8 will be interpreted as having the same scope as claim 1 upon which it depends.
Note Regarding Administration of Lipid Nanoparticles
The examiner notes the following regarding administration of lipid nanoparticles, specifically related to the organ to which said lipid nanoparticles are delivered. Prior art teachings indicate that lipid nanoparticle delivery locations vary significantly by route of administration. See Lowe (“mRNA Vaccines: What Happens” https://www.science.org/content/blog-post/mrna-vaccines-what-happens accessed 3 April 2025, published 21 January 2021, 13 printed pages), relevant text reproduced below from the bottom of page 1 and the top of page 2.
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The above-reproduced text appears to indicate that intraperitoneal and intravenous administration results in hepatic delivery; however, intramuscular, subcutaneous, and intradermal administration results in substantial extrahepatic delivery.
Claim Interpretation
Claim 1 recites a pharmaceutical composition formulated for substantial extrahepatic delivery. The examiner notes that the claims do not recite the route of administration upon which said substantial extrahepatic delivery occurs. This is relevant because certain routes of administration are more likely to result in extrahepatic delivery as compared with other routes. For example, for a given pharmaceutical composition, the skilled artisan may have expected intradermal administration to have resulted in more extrahepatic delivery than intravenous administration of said composition; see the section of the office action set forth above entitled “Note Regarding Administration of Lipid Nanoparticles.”
For the purposes of examination under prior art, the examiner understands claim 1 to require substantial extrahepatic delivery under any route of administration. This may include routes of administration not specifically taught by the prior art. For example, a hypothetical prior art reference teaching a preparation that results in entirely hepatic delivery when administered intravenously could still read on the claimed requirements if it would have resulted in substantial extrahepatic delivery had it been administered intradermally, provided that said hypothetical prior art reference teaches all other claim limitations. This would have been the case even if the hypothetical prior art reference did not teach or suggest intradermal administration.
Regarding claims 6-7, the examiner notes that there is no requirement that the claimed lipid nanoparticle be delivered via the same route of administration as the reference lipid nanoparticle. As such, a case wherein the claimed lipid nanoparticle delivered intradermally resulted in more extrahepatic delivery as compared with the reference lipid nanoparticle delivered via intravenous administration.
Note Regarding Abbreviations
The instant claims include various abbreviations. For example, claims 14-15 recite PEG, which refers to polyethylene glycol. Claim 24 recites DOPE and DSPC; these refer to dioleoyl phosphatidylethanolamine and distearoyl phosphatidylcholine, and are well-known phospholipids in the art of liposomes and lipid nanoparticles. Claims 26-28 recite DNA, RNA, and mRNA; DNA refers to deoxyribonucleic acid, RNA to ribonucleic acid, and mRNA to messenger ribonucleic acid. Claim 25 recites various acronyms that are defined on the table bridging pages 15-16 of the specification, and refer to various lipids. Regarding the particular pegylated lipids in claim 15, these appear to be defined at least as of Lin et al. (US 2024/0335384 A1), paragraph 0066. The examiner understands DLPE to refer to dilauroyl phosphatidylethanolamine, DMPE to refer to dimyristoyl phosphatidylethanolamine, DPPC to refer to dipalmitoyl phosphatidylcholine, and DSPE to refer to distearoyl phosphatidylethanolamine. DOMG is defined in the instant specification on page 16, and DMG is defined in the instant specification on page 15.
Claim Rejections - 35 USC § 102(a)(1) - Anticipation
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 6-8, 14, 18-19, 22, 24, 27-28, 32, 36, 43 and 46 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hope et al. (US 2020/0121809 A1).
Hope et al. (hereafter referred to as Hope) is drawn to lipid nanoparticles, as of Hope, title and abstract. Said lipid nanoparticles are for delivery of RNA and comprise the following ingredients, as of Hope, paragraphs 0008-0014, reproduced below.
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Hope teaches the following embodiments on page 74, Table 7, reproduced below.
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The above nanoparticles encapsulate mRNA encoding luciferase which is used for testing purposes, as of Hope, page 73, Example 2, paragraph 0490. The abbreviation II-9 refers to a particular ionizable cationic lipid; see Hope, page 30, relevant figure reproduced below.
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As to claim 1(a), the claim requires a lipid nanoparticle comprising at least one ionizable lipid. Hope teaches this as of page 74, Table 7 of Hope.
As to claim 1(b), the claim requires a polynucleotide. The mRNA encoding luciferase taught by Hope, paragraph 0490, is understood to read on this requirement.
As to claim 1, the preamble of the claim requires substantial extrahepatic delivery, which appears to mean that at least about 5% of the polynucleotide delivery occurs in a target organ that is not the liver. Hope appears to teach an example where this is measured. See Hope, figures 1A and 1B, reproduced below with annotation by the examiner.
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The above-reproduced data for the II-9 3:1 embodiment appears to show about 6500 ng delivery to the liver and about 800 ng delivery to the spleen. The percentage going to the spleen appears to be the following:
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This would appear to result in about 10.9% going to the spleen, which exceeds the 5% minimum required by the claims.
The examiner additionally notes here that the data obtained in figures 1A and 1B appears to have been obtained via tail vein injection, which is a form of intravenous injection. See Hope, paragraph 0490. The skilled artisan would have expected that had the lipid nanoparticle of Hope been administered intradermally, there would have been more than 5% delivery to the organs of the lymphatic system rather than to the liver. The skilled artisan would have expected this to have been the case in a lipid nanoparticle comprising an ionizable cationic lipid regardless of the chemical structure of the ionizable cationic lipid used. See the sections above entitled “Note Regarding Administration of Lipid Nanoparticles” and “Claim Interpretation.” Something which is old (e.g. the composition of Lin) does not become patentable upon the discovery of a new property (that the composition would have been capable of extrahepatic delivery upon certain routes of administration), and this feature need not have been recognized at the time of filing. See MPEP 2112(I & II); also see MPEP 2112(V).
As to claims 6-7, the examiner notes that these claims are interpreted as there being no requirement that the claimed lipid nanoparticle be delivered via the same route of administration as the reference lipid nanoparticle. As such, a case wherein the lipid nanoparticle delivered intradermally resulted in more extrahepatic delivery as compared with the reference lipid nanoparticle delivered via intravenous administration is understood to be within the claim scope. See the section above entitled “Claim Interpretation.” The skilled artisan would have expected that the composition of Hope administered intradermally would have had more extrahepatic delivery as compared with a composition with the reference lipid administered intravenously.
As to claim 8, this claim is rejected for essentially the same reason that claim 1 is rejected. See the above rejection of claim 8 under 35 U.S.C. 112(b) along with an explanation as to how the claim is interpreted.
As to claim 14, the examiner understands the term “PEGA”, as of Hope, page 74, Table 7.
As to claims 18-19, Hope teaches cholesterol, as of Hope, page 74, Table 7.
As to claim 22, Hope teaches DSPC, which is a phospholipid, as of Hope, page 74, Table 7.
As to claim 24, Hope teaches DSPC, which is a phospholipid, as of Hope, page 74, Table 7.
As to claim 27, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490.
As to claim 28, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490.
As to claim 32, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490. Luciferase is understood to be the encoded protein.
As to claim 36, Hope teaches delivery to the spleen, as of Hope, figures 1A and 1B; also see the explanation above of why claim 1 is rejected.
As to claim 43, Hope teaches about 10% of delivery to the spleen; see the rejection of claim 1 above.
As to claim 46, Hope teaches delivery to the spleen; the examiner understands the spleen to comprise an immune cell population.
Note Regarding Reference Date: Hope was published on 23 April 2020. This is earlier than the effective filing date of the instant application. Even if, purely en arguendo, the effective filing date of the instant application was understood to be 28 May 2021, Hope was still published over a year earlier than the effective filing date of the instant application. As such, Hope is understood to be prior art under AIA 35 U.S.C. 102(a)(1), and the AIA exceptions do not appear to be applicable.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1-2, 6-8, 14-15, 18-19, 22, 24-28, 32, 36, 42-43, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (US 2024/0335384 A1).
Lin et al. (hereafter referred to as Lin) is drawn to a cationic lipid and a cationic liposome or lipid nanoparticle comprising said cationic lipid, as of Lin, title, abstract, and paragraphs 0003-0004. The lipid nanoparticle comprises an ionizable cationic lipid, as of Lin, paragraph 0004. This is used to deliver nucleic acids such as mRNA or siRNA, as of Lin, paragraph 0077. The ionizable cationic lipid of Lin may have the following structure, as of Lin, page 88, structure on bottom of page, which is shown below next to compound 1.
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That the nucleic acid is encapsulated is taught as of Lin, page 78, paragraph 0395, Table 1 of Lin.
As to claim 1, Lin is not understood to anticipate claim 1 because the lipid taught by Lin is taught in a long list of ionizable cationic lipids, and Lin does not appear to exemplify a lipid nanoparticle comprising this particular lipid in the examples of Lin. Nevertheless, While the prior art teaches all of the claimed components, the prior art is not anticipatory insofar as these components must be selected from various lists/locations in the prior art reference. It would have been prima facie obvious; however, to have selected the recited components from various lists/locations in the prior art reference and to have combined them together. This is because such a modification would have represented nothing more than the predictable use of prior art components according to their established functions. Combining separate prior art components (from a single prior art reference) according to known methods to yield predictable results is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 1, the claim requires that the lipid nanoparticle has substantial (i.e. >5%) extrahepatic delivery, targeting an organ that is not the liver. The skilled artisan would have expected that had the lipid nanoparticle of Lin been administered intradermally, there would have been more than 5% delivery to the organs of the lymphatic system rather than to the liver. The skilled artisan would have expected this to have been the case in a lipid nanoparticle comprising an ionizable cationic lipid regardless of the chemical structure of the ionizable cationic lipid used. See the sections above entitled “Note Regarding Administration of Lipid Nanoparticles” and “Claim Interpretation.” Something which is old (e.g. the composition of Lin) does not become patentable upon the discovery of a new property (that the composition would have been capable of extrahepatic delivery upon certain routes of administration), and this feature need not have been recognized at the time of filing. See MPEP 2112(I & II); also see MPEP 2112(V).
As to claim 2, Lin teaches Compound 1, as explained above.
As to claims 6-7, the examiner notes that these claims are interpreted as there being no requirement that the claimed lipid nanoparticle be delivered via the same route of administration as the reference lipid nanoparticle. As such, a case wherein the lipid nanoparticle delivered intradermally resulted in more extrahepatic delivery as compared with the reference lipid nanoparticle delivered via intravenous administration is understood to be within the claim scope. See the section above entitled “Claim Interpretation.” The skilled artisan would have expected that the composition of Lin administered intradermally would have had more extrahepatic delivery as compared with a composition with the reference lipid administered intravenously.
As to claim 8, this claim is rejected for essentially the same reason that claim 1 is rejected. See the above rejection of claim 8 under 35 U.S.C. 112(b) along with an explanation as to how the claim is interpreted.
As to claim 14, Lin teaches a PEGylated lipid in paragraph 0066.
As to claim 15, Lin teaches PEG-DMG and PEG-DSPE in paragraph 0066.
As to claims 18-19, Lin teaches cholesterol as of paragraph 0068.
As to claim 22, Lin teaches a phospholipid in paragraph 0067.
As to claim 24, Lin teaches DSPC in paragraph 0397 and DOPE in paragraphs 0067 and 0195.
As to claim 25, Lin teaches DOTAP and DDAB in paragraph 0065. The skilled artisan would have been motivated to have used multiple cationic lipids together in the lipid nanoparticle of Lin. Combining prior art elements (e.g. multiple cationic lipids; namely, the lipid on page 88 of Lin as well as DOTAP and/or DDAB) according to known methods to yield predictable results (formation of a lipid nanoparticle capable of delivering a nucleic acid) is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 26, Lin teaches delivery of DNA in paragraph 0075.
As to claims 27-28, Lin teaches mRNA in paragraph 0077.
As to claim 32, Lin teaches mRNA that expresses (i.e. encodes) luciferase, which is a protein, as of paragraph 0078 of Lin. Lin generally teaches that the mRNA may encode a polypeptide in paragraph 0077, wherein the examiner understands the term “polypeptide” and “protein” to have essentially the same meaning.
As to claim 36, the skilled artisan would have expected that intradermal administration of the lipid nanoparticle of Lin would have resulted in administration to the skin and lymphatic system (which is part of the immune system). See the section above entitled “Note Regarding Administration of Lipid Nanoparticles.” The skilled artisan would also have expected that intramuscular administration of the lipid nanoparticle of Lin would have resulted in administration to the muscle.
As to claim 42, Lin teaches a targeting group to achieve targeting function in the abstract, and teaches attaching ligands in paragraph 0003. Lin teaches a folate group in paragraph 0125, wherein folate is a well-known targeting ligand.
As to claim 43, the skilled artisan would have expected that had the lipid nanoparticle of Lin been administered intradermally, there would have been more than 10% delivery to the organs of the lymphatic system rather than to the liver. The skilled artisan would have expected this to have been the case in a lipid nanoparticle comprising an ionizable cationic lipid regardless of the chemical structure of the ionizable cationic lipid used. See the sections above entitled “Note Regarding Administration of Lipid Nanoparticles” and “Claim Interpretation.”
As to claim 46, this claim is rejected for the same reason that claim 43 is rejected because the examiner understands the lymphatic system to be part of the immune system. Lin also teaches mRNA encoding antigens in paragraph 0004, wherein said antigen is recognized by antigen-specific T-cells, as of paragraph 0081.
Note Regarding Filing and Reference Dates: The instant application is understood to have an effective filing date of 27 May 2022. See the section above entitled “Priority.” Lin is understood to have an effective filing date as early as 15 October 2021 based upon a foreign priority claim; see relevant data reproduced below from the front page of Lin.
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As such, Lin is understood to have been effectively filed earlier than the effective filing date of the instant application. Therefore, Lin is prior art under AIA 35 U.S.C. 102(a)(2). There examiner additionally notes that Lin does not appear to have a common inventor with the instant application; as such, it appears as if the AIA exception under AIA 35 U.S.C. 102(b)(1)(A) would be unlikely to be applicable.
Claim(s) 1, 6-8, 14-15, 18-19, 22, 24-28, 32, 36, 42-43, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hope et al. (US 2020/0121809 A1) in view of de Koker et al. (WO 2019/141814 A1).
Hope is drawn to lipid nanoparticles encapsulating nucleic acids. Hope suggests delivery to the spleen as of at least paragraph 0035. See the rejection above over Hope by itself.
For the purposes of this rejection, purely en arguendo and in regard to this ground of rejection only, the examiner takes the position that Hope fails to teach a lipid nanoparticle that exhibits substantial extrahepatic delivery.
De Koker et al. (hereafter referred to as de Koker) is drawn to lipid nanoparticles, as of de Koker, title and abstract. De Koker teaches the following, as of de Koker, page 5, relevant text reproduced below.
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De Koker teaches high ratios of liver to spleen expression as of figure 6, reproduced below.
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De Koker teaches that preferential targeting of the spleen would appear to increase immunogenicity, as of page 13, relevant text reproduced below; the examiner understands this to refer to cases in which the mRNA delivers a vaccine to which an immune response is desired.
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For the purposes of this rejection, the examiner takes the position that the ionizable lipid of de Koker differ from the claimed ionizable lipid.
It would have been prima facie obvious for one of ordinary skill in the art to have modified the particle size of the lipid nanoparticle of Hope to have increased targeting to the spleen. Hope is drawn to lipid nanoparticles for delivering nucleic acid, and suggests delivery to the spleen. De Koker indicates that delivery to the spleen may be enhanced by increasing the particle size. As such, the skilled artisan would have been motivated to have optimized the composition of Hope by increasing the particle size in order to have predictably increased delivery to the spleen with a reasonable expectation of success.
As to claims 6-7, the examiner notes that these claims are interpreted as there being no requirement that the claimed lipid nanoparticle be delivered via the same route of administration as the reference lipid nanoparticle. As such, a case wherein the lipid nanoparticle delivered intradermally resulted in more extrahepatic delivery as compared with the reference lipid nanoparticle delivered via intravenous administration is understood to be within the claim scope. See the section above entitled “Claim Interpretation.” The skilled artisan would have expected that the composition of Hope administered intradermally would have had more extrahepatic delivery as compared with a composition with the reference lipid administered intravenously.
As to claim 8, this claim is rejected for essentially the same reason that claim 1 is rejected. See the above rejection of claim 8 under 35 U.S.C. 112(b) along with an explanation as to how the claim is interpreted.
As to claim 14, the examiner understands the term “PEGA”, as of Hope, page 74, Table 7.
As to claim 15, Hope teaches PEG-DMG along with other PEGylated lipids in paragraph 0440.
As to claims 18-19, Hope teaches cholesterol, as of Hope, page 74, Table 7.
As to claim 22, Hope teaches DSPC, which is a phospholipid, as of Hope, page 74, Table 7.
As to claim 24, Hope teaches DSPC, which is a phospholipid, as of Hope, page 74, Table 7.
As to claim 25, Hope teaches DODAP in paragraphs 0184-0185.
As to claim 26, Hope teaches encapsulating plasmid DNA in paragraph 0043.
As to claim 27, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490.
As to claim 28, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490.
As to claim 32, Hope teaches mRNA encoding luciferase, as of Hope, paragraph 0490. Luciferase is understood to be the encoded protein.
As to claim 36, Hope teaches delivery to the spleen, as of Hope, figures 1A and 1B; also see the explanation above of why claim 1 is rejected.
As to claim 42, Hope teaches a monoclonal or polyclonal antibody to assist the delivery of the lipid nanoparticle, as of Hope, paragraph 0465. These would appear to be ligands that may be connected to the particle, as of Hope, paragraphs 0213, 0219-0220, and claim 38 of Hope, wherein the term “ligand” is understood to refer to a targeting ligand.
As to claim 43, Hope teaches about 10% of delivery to the spleen; see the rejection of claim 1 above.
As to claim 46, the skilled artisan would have expected that administration to the spleen would have resulted in targeting an immune cell, as per the rationale provided by de Koker.
Claim(s) 1-2, 6-8, 14-15, 18-19, 22, 24-28, 32, 36, 42-43, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (US 2024/0335384 A1) in view of de Koker et al. (WO 2019/141814 A1).
Lin is drawn to a lipid nanoparticle comprising an ionizable cationic lipid for delivery of a nucleic acid. See the rejection above over Lin by itself. Lin teaches an antigen in paragraph 0081, indicates that the mRNA may encode an antigen in paragraph
For the purposes of this ground of rejection, the examiner takes the position that, purely en arguendo and in regard to this ground of rejection only, Lin fails to teach the required non-liver delivery.
De Koker et al. (hereafter referred to as de Koker) is drawn to lipid nanoparticles, as of de Koker, title and abstract. De Koker teaches the following, as of de Koker, page 5, relevant text reproduced below.
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De Koker teaches high ratios of liver to spleen expression as of figure 6, reproduced below.
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De Koker teaches that preferential targeting of the spleen would appear to increase immunogenicity, as of page 13, relevant text reproduced below; the examiner understands this to refer to cases in which the mRNA delivers a vaccine to which an immune response is desired.
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For the purposes of this rejection, the examiner takes the position that the ionizable lipid of de Koker differ from the claimed ionizable lipid.
For the purposes of this rejection, the examiner takes the position that the ionizable lipid of de Koker differ from the claimed ionizable lipid.
It would have been prima facie obvious for one of ordinary skill in the art to have modified the particle size of the lipid nanoparticle of Lin to have increased targeting to the spleen, and thereby to have increased immunogenicity, as of de Koker, paragraph 0102. Lin is drawn to lipid nanoparticles for delivering nucleic acid, and suggests genetic vaccines and encoding an antigen against which an immune response is desired. De Koker indicates that delivery to the spleen may be enhanced by increasing the particle size, and also teaches that increased delivery to the spleen results in more immunogenicity. As such, the skilled artisan would have been motivated to have optimized the composition of Lin by increasing the particle size in order to have predictably increased immunogenicity by predictably increasing delivery to the spleen with a reasonable expectation of success. Although Lin does not explicitly teach delivery to the spleen, Lin does teach a genetic vaccine comprising a nucleic acid against which an immune response is desired. As de Koker teaches that improved delivery to the spleen results in improved immunogenicity, as of de Koker, page 13, the skilled artisan would have been motivated to have modified the lipid nanoparticle of Lin to have increased delivery to the spleen in order to have predictably improved immunogenicity of the encoded antigen with a reasonable expectation of success.
Additional Relevant Prior Art
As additional relevant prior art, the examiner cites Sgouros et al. (US 2011/0165223 A1). Sgouros et al. (hereafter referred to as Sgouros) is drawn to antitumor immunization by administration of a pegylated liposome to the spleen, as of Sgouros, title and abstract. Sgouros teaches a particle size of greater than about 300 nm to target the spleen, as of Sgouros, abstract. Sgouros teaches a liposome in the 300-600 nm range in paragraph 0040.
The examiner notes that in selecting the references to be used in rejecting the claims, the examiner should carefully compare the references with one another and with the applicant’s disclosure to avoid an unnecessary number of rejections over similar references. The examiner is not called upon to cite all references that may be available, but only the "best." (See 37 CFR 1.104(c).) Multiplying references, any one of which is as good as, but no better than, the others, adds to the burden and cost of prosecution and should therefore be avoided. See MPEP 904.03.
In this case, the examiner takes the position that Sgouros is not as good of a reference as de Koker. This is because Sgouros, while drawn to a liposomal vaccine, does not appear to be drawn to a nucleic acid vaccine; in contrast, Sgouros is drawn to a vaccine with a peptide/protein antigen, as of Sgouros, paragraph 0027. Also, there is no evidence that the liposome of Sgouros is cationic. As such, for at least these reasons, Sgouros is not as close to the claimed invention as is de Koker. With that being said, the general teachings of Sgouros indicate that liposomes in a particular size range are more likely to target the spleen as compared with liposomes outside that size range. As such, the teachings of Sgouros appear to support the teachings of de Koker which indicate that the skilled artisan would have been motivated to have optimized the particle size of the lipid nanoparticle in order to increase spleen delivery and to have increase immunogenicity of a vaccine.
Conclusion
No claim is allowed.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612