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.
Priority
The instant application is a 371 of PCT/EP2022/079345 filed on 10/21/2022 and claims foreign priority to EP21382960.9 filed on 10/22/2021, EP21382959.1 filed on 10/22/2021, EP21382958.3 filed on 10/22/2021, EP21382961.7 filed on 10/22/2021, EP21383082.1 filed on 11/30/2021, EP22382515.9 filed on 05/30/2022, EP22382516.7 filed on 05/30/2022, EP22382517.5 filed on 05/30/2022, EP22382518.3 filed on 05/30/2022, and EP22382514.2 filed on 05/30/2022. The certified copies of the foreign priority applications filed on 04/19/2024 are acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/20/2024 and 03/21/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 12/20/2024 is acknowledged. Claims 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 50, 53-54, 57, 61-62, 66-67, 69-70, 72, and 74 are amended. Claims 3, 5-6, 8-9, 12-13, 15-16, 19-20, 22, 24-27, 29, 31-49, 51-52, 55-56, 58-60, 63-65, 68, 71, and 76-79 are cancelled.
Accordingly, claims 1-2, 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 50, 53-54, 57, 61-62, 66-67, 69-70, and 72-75 are pending and being examined on the merits herein.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 21, and 70 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 2 recites “polyalkylene glycols (e.g., polyethylene glycol)”.
Claim 2 is indefinite because it is unclear if the recited parenthetical “(e.g., polyethylene glycol)” is merely exemplary and therefore not required, or is a required feature of the claim.
Claim 21 recites “… wherein the helper lipid is selected from the group consisting of …, more preferably selected from the group consisting of …”.
Claim 21 is indefinite because the recited “more preferably” is exemplary language, and it is not clear if the recited groups following the exemplary phrase is merely exemplary and therefore not required, or is a required feature of the claim.
Claim 70 recites “wherein the cationic oligosaccharide is selected from Table 1 or Table 2”.
MPEP 2173.05(s) states that “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.”
While Tables 1 and 2 discloses many compounds, it is possible to recite all of these compound structures into the claim in order to be complete in itself. Therefore, the incorporation by reference of the tabled are not a necessity.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-2, 4, 7, 10, 14, 17-18, 21, 23, 28, 30, and 72-75 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US20170326255A1 in PTO-892) in view of Thomas (WO2021000041A1 in PTO-892).
Zhang discloses sucrose ester based cationic lipids for delivery of nucleic acids and compositions including thereof (Abstract). Zhang discloses that gene therapy is a new and revolutionary method for treating cancers and other disease but have limitations due to problems with efficient gene delivery (paragraph 0002).
The structure of the sucrose ester based cationic lipid compound is shown in Claim 1 and below
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The Y groups are selected from —NRaRb and —N+RaRbRcX−, wherein Ra, Rb and Rc are the same or different, and are selected from hydrogen, C1-6 hydroxyl, C1-6 hydroxyalkyl, galactosyl, mannosyl and/or folic acid ester group; X− is selected from F−, Cl−, Br−, I−.
The compound shown above in Zhang meets the structural limitations of the recited cationic oligosaccharide because a cationic moiety (Y group) is bonded to a sucrose.
Zhang discloses a cationic lipid composition that consists of the above sucrose ester based cationic lipid compound and a co-lipid, and the mass ratio of the sucrose ester cationic lipid compound to the co-lipid is from 10:1 to 1:10 (claim 4). Zhang discloses the co-lipid is selected from cholesterol and others (claim 5). Zhang also discloses the co-lipid can be DOPC and others (paragraph 0030).
Zhang also demonstrates preparation of their cationic liposomes in Example 4 (paragraph 0062), in which sucrose ester based cationic lipids were mixed with DOPE at molar ratios of 2:1 and others (ester cationic lipid : DOPE) or with cholesterol at molar ratios such as 2:1 and others (ester cationic lipid : cholesterol).
Zhang also demonstrates in Example 5 that the particle size of the cationic liposomes ranged from 100 to 350 nm (paragraph 0063).
Zhang discloses that the cationic lipid composition is further combined nucleic acids at a mass ratio of the cationic lipid composition to the nucleic acid of 20:1 to 1:20 (claim 7). Zhang discloses that the nucleic acid can be pDNA, microRNA, and siRNA (claim 8).
Zhang demonstrates in Example 8 that their cationic lipid compositions were effective in delivering DNA to a cell experiment as demonstrated by the enhanced expression in the targeted cells (FIG. 7-8).
While Zhang teaches a complex comprising the recited cationic oligosaccharide and a recited one or more additive, Zhang does not teach further including a recited surfactant such as polysorbate with their complex.
Thomas discloses a similar sugar- ionizable lipid-based compounds that are useful for the
delivery of nucleic acids and compositions thereof (Abstract, claim 1, and paragraph 00105). Thomas further discloses that these compounds can be mixed with a stabilizing agent and other lipid components such that the compound is present at about 10-90 mol% and the stabilizing agent is present at about 0-10 mol% (paragraph 00112). Thomas discloses that the stabilizing agent can be polysorbate 80 and others (paragraph 00117).
Thomas discloses that the lipid particles can have a mean particle diameter size of 50 to 150 nm (paragraph 00175). Thomas further discloses that smaller particles generally exhibit increased circulatory lifetime in vivo compared to larger particles and that smaller particles have an increased ability to reach tumor sites than larger nanoparticles (paragraph 00175). Thomas discloses that their compositions can include various therapeutic agents such as siRNA, self-amplifying RNA (SAM), and others (paragraph 00195). The self-amplifying RNA disclosed in Thomas is the same as the recited saRNA (self-amplifying RNA). Thomas discloses their compositions are effective for delivering active agents to the lung (paragraph 00200) and for use in cancer therapies (paragraph 00119). Thomas discloses that their invention also provides methods for introducing nucleic acids into the cell for the purpose of transcription, translation, and expression of the delivered genes (paragraph 00188).
It would have been prima facie obvious before the effective filing date of the claimed invention
to have further included into the cationic lipid composition of Zhang the polysorbate 80 as disclosed in Thomas and further prepare the sucrose ester based cationic lipid compound of Zhang at 10-90 mol% and the polysorbate at 0-10 mol% as disclosed in Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known
methods to yield predictable results and would have a reasonable expectation of success in doing so
because Thomas provides guidance of including polysorbate as a stabilizing agent with a similar sugar-
ionizable lipid-based compound that has the same purpose of gene delivery.
Furthermore, the modified complex would have mol% amounts that overlap in molar ratio of the cationic oligosaccharide to the polysorbate, rendering the recited molar ratio in instant claim 4 obvious. See MPEP 2144.05 I.
In regards to instant claim 10, It would have also been prima facie obvious before the effective filing date of the claimed invention to select self-amplifying RNA as the nucleic acid that is included in the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because both Zhang and Thomas disclose similar sugar cationic lipid compositions that include several of the same components that are useful for the same purpose of nucleic acid delivery.
In regards to instant claim 14, it would have also been prima facie obvious before the effective filing date of the claimed invention to prepare the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above to have lipid particle sizes of 50 to 150 nm in diameter as disclosed in Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to prepare the lipid particles at 50 to 150 nm in diameter because Thomas discloses that smaller particles generally exhibit increased circulatory lifetime in vivo compared to larger particles and that smaller particles have an increased ability to reach tumor sites than larger nanoparticles (paragraph 00175)
One of ordinary skill in the art would have a reasonable expectation of success because both Zhang and Thomas disclose similar sugar cationic lipid compositions that include several of the same components that are useful for the same purpose of nucleic acid delivery.
In regards to instant claim 28, it would have also been prima facie obvious before the effective filing date of the claimed invention to modify the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above by including both the DOPE at a molar ratio of 2:1 and the cholesterol at a molar ratio of 2:1 as disclosed in Zhang to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known
methods to yield predictable results and would have a reasonable expectation of success in doing so because Zhang provides guidance that their cationic lipid composition can include a mixture of two or more co-lipids, which include cholesterol and DOPE, and further demonstrates preparing liposomes using either cholesterol and DOPE at a molar ratio of 2:1 (sucrose cationic lipid : co-lipid).
In regards to instant claim 30, instant claim 30 depends from instant claim 1. Instant claim 1 recites that the complex comprises one or more additives is selected from a sterol, a helper lipid, an immunomodulator, and a targeting molecule. While instant claim 30 further limits the recited immunomodulator, instant claim 30 does not necessarily require that the recited one or more additives are an immunomodulator. Therefore, since instant claim 1 was rendered obvious over an alternative recited additive, instant claim 30 is also rendered obvious.
In regards to instant claims 72-73, it would have also been prima facie obvious before the effective filing date of the claimed invention to administer the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above to the lung to cause increased expression of RNA as disclosed in Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Thomas provides guidance of using cationic lipid compositions to deliver genes to the lung and cause increased expression of the delivered gene.
In regards to instant claims 74-75, it would have also been prima facie obvious before the effective filing date of the claimed invention to administer the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above to treat cancer as disclosed by Zhang and Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because both Zhang and Thomas provides guidance of using their respective cationic lipid compositions to deliver genes for cancer treatment.
Claim(s) 11, 53-54, 57, 61-62, 66-67, 69-70 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US20170326255A1 in PTO-892) in view of Thomas (WO2021000041A1 in PTO-892), as applied to claim 1 above, and further in view of Carbajo-Gordillo (in IDS filed 12/20/2024).
The combined teachings of Zhang and Thomas are as described above and teach the complex of instant claim 1 as discussed above.
The combined teachings, however, do not teach the cationic oligosaccharide is a compound of the instant formula I and that the complex has N/P ratio of less than 20:1 as recited in instant claim 11.
Carbajo-Gordillo teaches trehalose-based Siamese twin amphiphiles with tuneable self-assembling, DNA nanocomplexing and gene delivery properties (Abstract).
Carbajo-Gordillo teach that gene therapy treatment such as for cancers have strongly nurtured expectations of a new age for personalized medicine, however the main hurdle for these treatment is the lack of delivery vectors capable of efficiently and safely transporting the therapeutic gene material to enforce the desired genetic change in the target cells (first paragraph left column page 8227). Several methods have been developed to overcome this limitation such as the use of cationic polymers. However, there is still a lack of precise structure-efficiency relationship and optimization studies (right column page 8227). Therefore, Carbajo-Gordillo developed their trehalose-based compound for efficient DNA nanocomplexation and delivery in vitro and in vivo.
Carbajo-Gordillo teaches their amphiphile compounds having the following structure shown in Scheme 1:
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Compound 8 in Carbajo-Gordillo is identical to JRL13 of Table 1 recited in instant claim 70 (page 104 of the instant specification), and meets all of the structural limitations recited in instant claims 53-54, 57, 61-62, 66-67, and 69.
Carbajo-Gordillo further discloses that these compounds were assessed for their gene delivery capabilities and as seen in FIG. 4 (page 8230), all of the developed compounds had increased gene transfection efficiency over controls. Carbajo-Gordillo further discloses that all of the compound formulations showed low cytotoxicity as well (second paragraph right column page 8229). Carbajo-Gordillo also discloses that the trehalose compounds were formulated at N/P ratios of 5, 10, and 20, and in all three ratios, full DNA complexation, compaction, and protection were achieved (last paragraph left column page 8227 through first paragraph right column page 8228).
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the sucrose ester based cationic lipid compound in the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas with the compound 8 trehalose-based amphiphile compound as disclosed in Carbajo-Gordillo to arrive at the claimed invention.
One of ordinary skill in the art would have substituted one known element (sucrose ester based cationic lipid compound) for another (compound 8 trehalose-based amphiphile compound) to obtain predictable results and would have a reasonable expectation of success in doing so because both the combined teachings of Zhang and Thomas and Carbajo-Gordillo teach the use of similar sugar-cationic compounds that complex with nucleic acids to improve its delivery into target cells.
In regards to instant claim 11, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared the cationic lipid composition as disclosed by the combined teachings of Zhang, Thomas, and Carbajo-Gordillo at a N/P ratio of 5, 10, and 20 as disclosed in Carbajo-Gordillo to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Carbajo-Gordillo provides that a N/P ratio of 5, 10, and 20 were all suitable for full DNA complexation, compaction, and protection with the trehalose-based compound.
Claim(s) 30 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US20170326255A1 in PTO-892) in view of Thomas (WO2021000041A1 in PTO-892), as applied to claim 1, and further in view of Chen et al. (Journal of Controlled Release, 2018 in PTO-892).
The combined teachings of Zhang and Thomas are as described above and teach the complex of instant claim 1 as discussed above. Furthermore, Zhang teaches that the sucrose ester based cationic lipid complex has lox toxicity and high transfection efficiency (Abstract).
The combined teachings, however, do not teach including an immunomodulator and in a molar ratio of cationic oligosaccharide to the immunomodulator of 1:0.05 to about 1:0.5.
Chen teaches the incorporation of dexamethasone prodrugs to suppress the immunostimulatory effects of lipid nanoparticle formulations of nucleic acids (Abstract).
Chen teaches that delivery of nucleic acids requires sophisticated delivery vehicles such as LNPs that contain ionizable amino-lipids are the most clinically advanced delivery system for nucleic acid therapeutics (left column paragraph page 46). Chen teaches that lipid nanoparticles (LNPs) are playing a leading role in enabling clinical applications of gene therapies based on DNA or RNA polymers (Abstract). However, one factor impeding clinical acceptance of LNP therapeutics is that LNP formulations of nucleic acid polymers can be immunostimulatory, necessitating co-administration of potent corticosteroid immunosuppressive agents (Abstract).
Therefore, Chen developed hydrophobic prodrugs of a potent corticosteroid, dexamethasone, that can be readily incorporated into LNP systems (Abstract).
Chen teaches the dexamethasone prodrug (LD001-LD005) was incorporated at 10mol% at expense of amino-lipid (last two paragraphs right column page 47), which is a molar ratio of 1:0.1 amino-lipid to dexamethasone prodrug.
Chen demonstrates in Figs. 4-7 (pages 50-53) that the 10 mol% dexamethasone prodrug incorporated LNPs effectively suppresses production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and further concludes that incorporation of hydrophobic prodrugs such as LD003 into LNP systems could provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations (Abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the cationic lipid composition as disclosed by the combined teachings of Zhang and Thomas described above the dexamethasone prodrug at 10 mol% of the cationic oligosaccharide disclosed in Chen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to include the dexamethasone prodrug at 10 mol% of cationic oligosaccharide because Chen demonstrates that the incorporation of their dexamethasone prodrugs into lipid nanoparticle formulations of nucleic acids effectively suppressed production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and can provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations.
One of ordinary skill in the art would have a reasonable expectation of success because both the combined teachings of Zhang and Thomas described above and Chen disclose the use of ionizable lipid compositions that are useful for the same purpose of nucleic acid delivery and reduce toxicity. Furthermore, Chen demonstrates that 10 mol% of a lipid-based compound was suitable to suppress the unwanted immunostimulatory effects.
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 1-2, 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 53-54, 57, 61-62, 66-67, 69-70, and 72-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,863 (‘863) in view of Zhang et al. (US20170326255A1 in PTO-892)
The claims of ‘863 recite a complex comprising the compound of claim 1 of ‘863 and a nucleic acid such as modRNA (claims 21 and 23). The claims of ‘863 recite that the complex has a ratio of N/P of less than 20:1, a diameter of 30 nm to 300 nm (claim 26), and further comprising a polysorbate at a molar ratio of 1:0.0075 to 1:3 (claims 28-30). The claims of ‘863 recite a method of increasing expression of RNA in a target such as the lungs or liver by administering the complex (claims 31-32) as well as a method of treating a disease such as cancer by administering the complex (claims 33-34).
Furthermore, the claims of ‘863 recite all of the same structural limitations of the recited cationic oligosaccharide as the instant cationic oligosaccharide (claims 1-2, 5, 7, 9-10, 13-19), and further recites the oligosaccharide is selected from Table 1 (claim 20), which includes the same compounds such as JLF19 (page 58 in the specification of ‘863). This JLF19 compound meets the structural limitation of the recited compound in the instant claims.
The claims of ‘863, however, do not recite including one or more of the recited additives.
The teachings of Zhang are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the complex recited in the claims of ‘863 the DOPE at a molar ratio of 2:1 and the cholesterol at a molar ratio of 2:1 as disclosed in Zhang to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known
methods to yield predictable results and would have a reasonable expectation of success in doing so because Zhang provides guidance of a similar cationic lipid composition comprising a sugar cationic compound that can include a mixture of two or more co-lipids, which include cholesterol and DOPE, and further demonstrates preparing liposomes using either cholesterol and DOPE at a molar ratio of 2:1 (sucrose cationic lipid : co-lipid).
In regards to instant claim 30, instant claim 30 depends from instant claim 1. Instant claim 1 recites that the complex comprises one or more additives is selected from a sterol, a helper lipid, an immunomodulator, and a targeting molecule. While instant claim 30 further limits the recited immunomodulator, instant claim 30 does not necessarily require that the recited one or more additives are an immunomodulator. Therefore, since instant claim 1 was rendered obvious over an alternative recited additive, instant claim 30 is also rendered obvious.
This reference application has the same patent term filing date as the instant application (10/21/2022). See MPEP 804 I.B.1.(b)(iii).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 30, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,863 (‘863) in view of Zhang et al. (US20170326255A1 in PTO-892) and Chen et al. (Journal of Controlled Release, 2018 in PTO-892).
The combination of the claims of ‘863 and Zhang are as described above and recite the complex of instant claim 1 as discussed above.
The combined references, however, do not recite including an immunomodulator and in a molar ratio of cationic oligosaccharide to the immunomodulator of 1:0.05 to about 1:0.5.
The teachings of Chen are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the cationic lipid composition as recited by the combination of the claims of ‘863 and Zhang described above the dexamethasone prodrug at 10 mol% of the cationic oligosaccharide disclosed in Chen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to include the dexamethasone prodrug at 10 mol% of cationic oligosaccharide because Chen demonstrates that the incorporation of their dexamethasone prodrugs into lipid nanoparticle formulations of nucleic acids effectively suppressed production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and can provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations.
One of ordinary skill in the art would have a reasonable expectation of success because both the combination of the claims of ‘863 and Zhang described above and Chen disclose the use of ionizable lipid compositions that are useful for the same purpose of nucleic acid delivery and reduce toxicity. Furthermore, Chen demonstrates that 10 mol% of a lipid-based compound was suitable to suppress the unwanted immunostimulatory effects.
Claims 1-2, 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 53-54, 57, 61-62, 66-67, 69-70, and 72-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,860 (‘860) in view of Zhang et al. (US20170326255A1 in PTO-892).
The claims of ‘860 recite a complex comprising a cationic oligosaccharide and an RNA, wherein the cationic oligosaccharides comprise a plurality of cationic moieties bonded to trehalose, a sucrose, or a gluco-n-oligosaccharide moiety, where n is 2-6, and a molar ratio of N/P in the complex is less than 20:1 (claim 1). The claims of ’860 recite the RNA is modRNA and others (claim 2), has a diameter of 30-300nm (claim 5), further comprises a suitable surfactant such as a polysorbate (claims 26-27), a molar ratio of oligosaccharide to surfactant of 1:0.00075 to about 1:3 (claim 28), and the same method of increasing expression of RNA in a target such as the lungs as well as a method of treating a disease such as an infection disease comprising administering the complex (claims 30-33).
Furthermore, the claims of ’860 recite all of the same structural limitations of the recited cationic oligosaccharide as the instant cationic oligosaccharide (claims 6-8, 11, 15-16, and 19-25), and further recites the oligosaccharide is selected from Table 1 (claim 29), which includes the same compounds such as JLF19 (page 62 in the specification of ‘860). This JLF19 compound meets the structural limitation of the recited cationic oligosaccharide in the instant claims.
The claims of ‘860, however, do not recite including one or more of the recited additives.
The teachings of Zhang are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the complex recited in the claims of ‘860 the DOPE at a molar ratio of 2:1 and the cholesterol at a molar ratio of 2:1 as disclosed in Zhang to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known
methods to yield predictable results and would have a reasonable expectation of success in doing so because Zhang provides guidance of a similar cationic lipid composition comprising a sugar cationic compound that can include a mixture of two or more co-lipids, which include cholesterol and DOPE, and further demonstrates preparing liposomes using either cholesterol and DOPE at a molar ratio of 2:1 (sucrose cationic lipid : co-lipid).
In regards to instant claim 30, instant claim 30 depends from instant claim 1. Instant claim 1 recites that the complex comprises one or more additives is selected from a sterol, a helper lipid, an immunomodulator, and a targeting molecule. While instant claim 30 further limits the recited immunomodulator, instant claim 30 does not necessarily require that the recited one or more additives are an immunomodulator. Therefore, since instant claim 1 was rendered obvious over an alternative recited additive, instant claim 30 is also rendered obvious.
This reference application has the same patent term filing date as the instant application (10/21/2022). See MPEP 804 I.B.1.(b)(iii).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 30, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,860 (‘860) in view of Zhang et al. (US20170326255A1 in PTO-892) and Chen et al. (Journal of Controlled Release, 2018 in PTO-892).
The combination of the claims of ‘860 and Zhang are as described above and recite the complex of instant claim 1 as discussed above.
The combined references, however, do not recite including an immunomodulator and in a molar ratio of cationic oligosaccharide to the immunomodulator of 1:0.05 to about 1:0.5.
The teachings of Chen are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the cationic lipid composition as recited by the combination of the claims of ‘860 and Zhang described above the dexamethasone prodrug at 10 mol% of the cationic oligosaccharide disclosed in Chen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to include the dexamethasone prodrug at 10 mol% of cationic oligosaccharide because Chen demonstrates that the incorporation of their dexamethasone prodrugs into lipid nanoparticle formulations of nucleic acids effectively suppressed production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and can provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations.
One of ordinary skill in the art would have a reasonable expectation of success because both the combination of the claims of ‘860 and Zhang described above and Chen disclose the use of ionizable lipid compositions that are useful for the same purpose of nucleic acid delivery and reduce toxicity. Furthermore, Chen demonstrates that 10 mol% of a lipid-based compound was suitable to suppress the unwanted immunostimulatory effects.
Claims 1-2, 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 53-54, 57, 61-62, 66-67, 69-70, and 72-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,857 (‘857) in view of Zhang et al. (US20170326255A1 in PTO-892) and Thomas (WO2021000041A1 in PTO-892).
The claims of ‘857 recite a complex comprising one of more compounds of claim 1 and an RNA (claim 25). The claims of 857 recite the RNA is modRNA and others (claim 27), a ratio of N/P in the complex is less than 20:1 (claim 28). has a diameter of 30-150nm (claim 30), the same method of treating a disease such as an infection disease comprising administering the complex (claims 33-34), and a method of delivery of the composition to a target such as the liver (claims 31-32).
Furthermore, the claims of ‘857 recite the same structural limitations as the instant cationic oligosaccharide (claims 1-2, 5, 7, 9-10, 14-17, and 23) and further recites the compound is selected from Table 1 (claim 24), which includes the same compounds such as JLF512 (page 57 in the specification of ‘857). This JLF512 compound meets the structural limitation of the recited instant cationic oligosaccharide in the instant claims.
The claims of ‘857, however, do not recite including a surfactant and one or more of the recited additives.
The independent teachings of Zhang and Thomas are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the complex recited in the claims of ‘857 the DOPE at a molar ratio of 2:1 and the cholesterol at a molar ratio of 2:1 as disclosed in Zhang as well as the polysorbate 80 at the mol% amounts disclosed in Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Zhang provides guidance of a similar cationic lipid composition comprising a sugar cationic compound that can include a mixture of two or more co-lipids, which include cholesterol and DOPE, and further demonstrates preparing liposomes using either cholesterol and DOPE at a molar ratio of 2:1 (sucrose cationic lipid : co-lipid). Furthermore, Thomas provides guidance of including polysorbate as a stabilizing agent with a similar sugar- ionizable lipid-based compound that has the same purpose of gene delivery, and the modified complex composition would have mol% amounts that overlap in molar ratios, rendering the recited molar ratio in the instant claims obvious. See MPEP 2144.05 I.
In regards to instant claim 30, instant claim 30 depends from instant claim 1. Instant claim 1 recites that the complex comprises one or more additives is selected from a sterol, a helper lipid, an immunomodulator, and a targeting molecule. While instant claim 30 further limits the recited immunomodulator, instant claim 30 does not necessarily require that the recited one or more additives are an immunomodulator. Therefore, since instant claim 1 was rendered obvious over an alternative recited additive, instant claim 30 is also rendered obvious.
In regards to instant claims 72-73, even though the combination of the claims of ‘857 and Zhang do not explicitly recite a method of increasing or causing increased expression of RNA in a target such as the liver in a subject, this increased RNA expression would flow naturally from the combined references because the combined references recites the same active step of delivering the same compound-RNA complex to the same target such as the liver in a subject.
This reference application has the same patent term filing date as the instant application (10/21/2022). See MPEP 804 I.B.1.(b)(iii).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 30, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,857 (‘857) in view of Zhang et al. (US20170326255A1 in PTO-892), Thomas (WO2021000041A1 in PTO-892), and Chen et al. (Journal of Controlled Release, 2018 in PTO-892).
The combination of the claims of ‘857, Zhang, and Thomas are as described above and recite the complex of instant claim 1 as discussed above.
The combined references, however, do not recite including an immunomodulator and in a molar ratio of cationic oligosaccharide to the immunomodulator of 1:0.05 to about 1:0.5.
The teachings of Chen are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the cationic lipid composition as recited by the combination of the claims of ‘857, Zhang, and Thomas described above the dexamethasone prodrug at 10 mol% of the cationic oligosaccharide disclosed in Chen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to include the dexamethasone prodrug at 10 mol% of cationic oligosaccharide because Chen demonstrates that the incorporation of their dexamethasone prodrugs into lipid nanoparticle formulations of nucleic acids effectively suppressed production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and can provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations.
One of ordinary skill in the art would have a reasonable expectation of success because both the combination of the claims of ‘857, Zhang, and Thomas described above and Chen disclose the use of ionizable lipid compositions that are useful for the same purpose of nucleic acid delivery and reduce toxicity. Furthermore, Chen demonstrates that 10 mol% of a lipid-based compound was suitable to suppress the unwanted immunostimulatory effects.
Claims 1-2, 4, 7, 10-11, 14, 17-18, 21, 23, 28, 30, 53-54, 57, 61-62, 66-67, 69-70, and 72-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,855 (‘855) in view of Carbajo-Gordillo (in IDS filed 11/05/2024), Zhang et al. (US20170326255A1 in PTO-892) and Thomas (WO2021000041A1 in PTO-892).
The claims of ‘855 recite a complex comprising the compound of claim 1 and an RNA (claim 18). The claims of ‘855 recite the RNA is modRNA and others (claim 20), a ratio of N/P in the complex is less than 20:1 (claim 21), has a diameter of 30-150nm (claim 23), the same method of treating a disease such as an infection disease comprising administering the complex (claims 26-27), and a method of delivery of the composition to a target such as the liver (claims 24-25).
Furthermore, the claims of ‘855 recite all of the same structural limitations as the instant compound (claims 1-2, 5, 7, 9, and 12-16) except the ‘855 compound recites a disulfide linkage instead of a single sulfide linkage and also does not recite the excluded provisos. Furthermore, the claims of ‘855 recite the compound is selected from Table 1 (claim 17), which includes the compounds such as PRX017 (page 53 in the specification of ‘855). This PRX017 compound also meets the structural limitation of the recited compound in the instant claims with the only difference also being the disulfide linkage instead of the single sulfide linkage and not reciting the excluded provisos.
Additionally, the claims of ‘855 do not recite including a surfactant and one or more of the recited additives.
The independent teachings of Carbajo-Gordillo, Zhang and Thomas are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to substituted the disulfide linkage recited in the claims of ‘855 with the single sulfide linkage as disclosed in Carbajo-Gordillo to arrive at the claimed invention.
One of ordinary skill in the art would have substituted one known element (disulfide linkage) for another (single sulfide linkage) to obtain predictable results and would have a reasonable expectation of success in doing so because both the claims of ‘855 and Carbajo-Gordillo recite nearly identical structures of trehalose-based siamese twin amphiphile compounds that are useful for the same purpose of gene delivery.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the complex recited in the claims of ‘855 the DOPE at a molar ratio of 2:1 and the cholesterol at a molar ratio of 2:1 as disclosed in Zhang as well as the polysorbate 80 at the mol% amounts disclosed in Thomas to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Zhang provides guidance of a similar cationic lipid composition comprising a sugar cationic compound that can include a mixture of two or more co-lipids, which include cholesterol and DOPE, and further demonstrates preparing liposomes using either cholesterol and DOPE at a molar ratio of 2:1 (sucrose cationic lipid : co-lipid). Furthermore, Thomas provides guidance of including polysorbate as a stabilizing agent with a similar sugar- ionizable lipid-based compound that has the same purpose of gene delivery, and the modified complex composition would have mol% amounts that overlap in molar ratios, rendering the recited molar ratio in the instant claims obvious. See MPEP 2144.05 I.
In regards to instant claim 30, instant claim 30 depends from instant claim 1. Instant claim 1 recites that the complex comprises one or more additives is selected from a sterol, a helper lipid, an immunomodulator, and a targeting molecule. While instant claim 30 further limits the recited immunomodulator, instant claim 30 does not necessarily require that the recited one or more additives are an immunomodulator. Therefore, since instant claim 1 was rendered obvious over an alternative recited additive, instant claim 30 is also rendered obvious.
In regards to instant claims 72-73, even though the combination of the claims of ‘857 and the teachings of Carbajo-Gordillo, Zhang and Thomas described above do not explicitly recite a method of increasing or causing increased expression of RNA in a target such as the liver in a subject, this increased RNA expression would flow naturally from the combined references because the combined references recites the same active step of delivering the same compound-RNA complex to the same target such as the liver in a subject.
This reference application has the same patent term filing date as the instant application (10/21/2022). See MPEP 804 I.B.1.(b)(iii).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 30, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/702,855 (‘855) in view of Carbajo-Gordillo (in IDS filed 11/05/2024), Zhang et al. (US20170326255A1 in PTO-892), Thomas (WO2021000041A1 in PTO-892), and Chen et al. (Journal of Controlled Release, 2018 in PTO-892).
The combination of the claims of ‘855, Carbajo-Gordillo, Zhang, and Thomas are as described above and recite the complex of instant claim 1 as discussed above.
The combined references, however, do not recite including an immunomodulator and in a molar ratio of cationic oligosaccharide to the immunomodulator of 1:0.05 to about 1:0.5.
The teachings of Chen are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included into the cationic lipid composition as recited by the combination of the claims of ‘855, Carbajo-Gordillo, Zhang, and Thomas described above the dexamethasone prodrug at 10 mol% of the cationic oligosaccharide disclosed in Chen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to include the dexamethasone prodrug at 10 mol% of cationic oligosaccharide because Chen demonstrates that the incorporation of their dexamethasone prodrugs into lipid nanoparticle formulations of nucleic acids effectively suppressed production of cytokines such as KC-GRO, TNFα, IL-1β and IL 6 following intravenous administration of LNP loaded with immune stimulatory oligodeoxynucleotides containing cytosine-guanine dinucleotide motifs, and can provide a convenient method for avoiding the immunostimulatory consequences of systemic administration of genetic drug formulations.
One of ordinary skill in the art would have a reasonable expectation of success because both the combination of the claims of ‘855, Carbajo-Gordillo, Zhang, and Thomas described above and Chen disclose the use of ionizable lipid compositions that are useful for the same purpose of nucleic acid delivery and reduce toxicity. Furthermore, Chen demonstrates that 10 mol% of a lipid-based compound was suitable to suppress the unwanted immunostimulatory effects.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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