DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Applicant’s preliminary claim amendment filed on January 9, 2025, has been received and entered. Claims 8, 10-14, 16, 18-20, 22, 24-26, and 28-34 have been amended. No have been cancelled or newly added. Claims 1-34 are pending in this instant application.
Priority
Acknowledgment is made of applicant's claim for priority to the filing dates of the PCT Application No. US2022/053465 filed on December 20, 2022; and United States Provisional Patent Application Serial No. 63/292,302 filed on December 21, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 30, 2025 are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 28 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 28, depends from claim 16 wherein the cationic or ionizable lipid in component (iii) possesses a secondary, tertiary, or quaternary amino group. However, claim 16 already recites (iii) at least one cationic or ionizable lipid containing a secondary, tertiary, or quaternary amino group. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-4 and 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019).
Ambati discloses administering a pharmaceutical composition comprising an effective amount of a compound via a lipid vehicle comprising nucleic acid (page 58- lines 16-26) in a subject with depleted microphages (page 82 lines 3-8).
Regarding claim 1, Ambati discloses a method of delivery of a nucleic acid (page 58 lines 25-30, page 65 lines 10-15, and page 82 lines 3-8)) with a lipid vehicle loaded with nucleic acid (page 58 lines 16 and 17) wherein the delivery vehicle has an average particle size of 0.1 to about 200 nanometers (page 68 line 32 through page 69 line 1) to a subject with the with depleted macrophages (page 82 lines 3-8).
Regarding claim 2, Ambati discloses a method for delivering nucleic acids into a subject comprising depleting the macrophages by injection of 200 µl clodronate liposomes on day 0 and then administering a nucleic acid (Alu RNA) into the subject (page 82 lines 3-8) wherein the delivery nucleic acid vehicle has an average particle size of 0.1 to about 200 nanometers (page 58 lines 25-30 and page 68 line 32 through page 69 line 1).
Claims 3 and 4, claim interpretation, recite small molecule drugs, paragraph [0025] recites multiple examples of small molecule drugs. In the interest of compact prosecution, small molecule drugs shall be given the meeting the broadest reasonable interpretation to include the small molecules exemplified in the specification and small molecules found in the prior art of record.
Regarding claims 3, 4, and 6 Ambati discloses depleting monocyte by the small molecule drug clodronate liposome (page 82 lines 3-8 and Fig. 19A).
Regarding claim 7, Ambati discloses wherein the depletion of microphages was achieved days 0 and day 2 (page 82 lines 3-8).
Regarding claims 8 and 9, Ambati discloses wherein the subject is a mammal including human, animals, primages, dogs, cattle sheep, pigs, rabbits, horses or mice (page 51 lines 9-12, page 65 lines 5-9, page 82 lines 3-8, and page 48 lines 6-13, page 58 lines 27-35).
Regarding claim 10, Ambati discloses polynucleotides transgeneses (aka inserted genes or expressed genes) that are taken up by the cell that express therapeutically useful proteins that are taken up by a cell (page 54 1-9 and page 82 lines 3-8).
Regarding claim 11, Ambati discloses wherein the nucleic acid or nucleic acid construct is a component of a gene editing machinery that incudes for an amino acid substitution and spicing into an expression vector construct (page 63 lines12-16, page 43 lines 8-10, and page 71 lines 25-38)
Regarding claim 12, Ambati discloses wherein the composition is delivered to the kidney (page 44 lines 10-11) and lungs (page 38 lines 30-35).
Regarding claim 13, Ambati discloses wherein the nucleic acid comprises miRNA (page 58 lines 27-28), siRNA (page 57 line 30 through page 58 line 1) and mRNA (page 9 line 6).
Regarding claim 14, Ambati discloses wherein the nucleic acid comprises mRNA (page 9 line 6) and a targeting agent that is stimulatory to the targeted molecule (page 53 lines52-53); wherein a ligand binds to a target molecule or peptide with a binding partner (page 40 line 21 and page 31 lines 9-10).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to deliver a nucleic acid with a nanoparticle lipid vehicle loaded with nucleic acid to a subject whose macrophages have been depleted as disclosed by Ambati, as instantly claimed, with a reasonable expectation of success at the time of filing as a matter of design choice. Said design choice amounting to combining prior art elements disclosed by Ambati according to known methods to yield predictable results of a method of delivering nucleic acids into a subject comprising injecting an agent known to deplete macrophages followed by the administration of a nucleic acid (Alu RNA) into the subject. One of ordinary skill in the art would be motivated to do so and have a reasonable expectation of success because Ambati had already disclosed such a method in order to treat diseases and disorders in a subject in need thereof (page 1 lines 27-30). It would have only required routine experimentation to modify the method of Ambati by injecting an agent known to deplete macrophages followed by the administration of a nucleic acid (Alu RNA) loaded into a lipid nanoparticle into the subject as required by the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary
skill in the art before the effective filing date of the claimed invention.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019) as applied to claims 2 above, and further in view of Revelo (Circulation Research, 2021; 129; 1086-1101).
Regarding claim 5, Ambati et al. remains as applied to claim 2 as fully set forth above. While Ambati teaches a method of delivery of a nucleic acid (page 58 lines 25-30, page 65 lines 10-15, and page 82 lines 3-8)) with a lipid vehicle loaded with nucleic acid (page 58 lines 16 and 17) wherein the delivery vehicle has an average particle size of 0.1 to about 200 nanometers (page 68 line 32 through page 69 line 1) to a subject with the with depleted macrophages (page 82 lines 3-8). Ambati fails to disclose wherein the antibodies are anti-CK115, anto-CCR2, anti-Ly6C, and anti-Gr-1.
However in the same field of endeavor delivery of moieties to deplete macrophages, Revelo discloses the delivery of anti-CK115 to deplete macrophages (pg 1093, col 1, para 1; pg 1093, col 2, para 1)
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to combine Ambati and Revelo for anti-CK115 to deplete macrophages as disclosed by Revelo in the method of depleting macrophages by administering a moiety as a matter of combining prior art elements according to known methods to yield predicable results, as instantly claimed, with a reasonable expectation of success. One of ordinary skill would be motivated to use anti-CK115 to deplete macrophages as a simple substitution of one know macrophage reducing agent for another with improved macrophage depletion effectiveness as evidenced by Revelo (pg 1093, col 2, para 1). One who would have practiced this invention would have had reasonable expectation of success because Ambati had already disclosed delivery of a microphage depletion agent, while Revelo provided guidance with respect to the administration of a different microphage depletion agent. It would have only required routine experimentation to substitute on microphage depletion agent for anther as required by the instantly claimed invention.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019) as applied to claims 1 and 14 in further view of the combination of Jiang et al. (Pub. No.: WO 2019/183637; Pub. Date: Sep. 26, 2019) here-in-after referred to as Jiang WO and Li et al. (Sci. Adv. 2020; 6 May 29, 2020).
Claim interpretation: claim 15 recites phosphoserine (PS) moiety, the instant specification provides examples of PS moieties to include more than phosphoserine including , 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), or a naturally-occurring PS-lipid, such as L-α-phosphatidylserine (brain) (para [0020]). As such phosphoserine (PS) moiety shall be interpreted to include a phosphate and serine group wherein additional chemical groups as part of the PS moiety are acceptable and still read on a phosphoserine (PS) moiety.
Regarding claim 15, Ambati et al. remains as applied to claims 1 and 14 fully set forth above. While Ambati teaches a method of delivery of a nucleic acid (page 58 lines 25-30, page 65 lines 10-15, and page 82 lines 3-8)) with a lipid vehicle loaded with nucleic acid (page 58 lines 16 and 17) wherein the delivery vehicle has an average particle size of 0.1 to about 200 nanometers (page 68 line 32 through page 69 line 1) to a subject with the with depleted macrophages (page 82 lines 3-8), and wherein the nanoparticle comprises a targeting agent that is stimulatory to the targeted molecule (page 53 lines52-53); wherein a ligand binds to a target molecule or peptide with a binding partner (page 40 line 21 and page 31 lines 9-10wo ).
But Ambati fails to disclose wherein the targeting ligand comprises phosphoserine moiety.
However, in the same field of endeavor of particles comprising lipids (claims 1, 4, and 5) for drug delivery of therapeutic agents (page 2 lines 20-22) Jiang WO discloses wherein the nanoparticle the nanoparticle comprises phosphoserine moieties (page 1 lines 22-30).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to combine Ambati and Jiang WO to include a phosphoserine moiety as part of a drug delivery vehicle as disclosed by Jiang WO in the lipid nanoparticle of Ambati as a matter of combining prior art elements according to known methods to yield predicable results, as instantly claimed, with a reasonable expectation of success. One of ordinary skill would be motivated to include the phosphoserine moiety in order to help promote immune tolerance even in inflamed regions as evidenced by Jiang WO (page 1 lines 19-21). Wherein phosphatidylserine with the PS as a head group serves as an immunomodulatory signal under physiological conditions in order to promote clearance of apoptotic cells additionally the PS molecule is found to trigger the release of regulatory cytokines by directly or indirectly interacting with the PS receptor on the immune cells as disclosed by Li et al. (page 1 last paragraph through page 2 first paragraph). One who would have practiced this invention would have had reasonable expectation of success because Ambati had already disclosed a lipid nanoparticle for delivery of a therapeutic agent while Jiang WO provided guidance with respect to additional of phosphoserine moieties to lipid therapeutic agent delivery vehicles. It would have only required routine experimentation to include phosphoserine as required by the instantly claimed invention.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claims 16-26, 28-30, and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019) as applied to claims 1 above, and further in view of the combination of Jiang et al. (Patent No.: US 8,617,592; Date of Patent: Dec. 31, 2013) and Yonezawa et al. (Advanced Drug Delivery Reviews, 154-155 (2020) 64-78).
Regarding claims 16 and 28, Ambati et al. remains as applied to claim 1. While Ambati teaches a method of delivery of a nucleic acid (page 58 lines 25-30, page 65 lines 10-15, and page 82 lines 3-8) with a lipid vehicle loaded with nucleic acid (page 58 lines 16 and 17) wherein the delivery vehicle has an average particle size of 0.1 to about 200 nanometers (page 68 line 32 through page 69 line 1) to a subject with the with depleted macrophages (page 82 lines 3-8). Ambati fails to disclose wherein the lipid nanoparticle comprises i) at least one zwitterionic polymer-containing lipid in which a lipid moiety is covalently attached to a zwitterionic polymer; (ii) at least one non-cationic lipid selected from charged and uncharged lipids, wherein the non- cationic lipid is not attached to a polymer;(iii) at least one cationic or ionizable lipid.
However in the same field of endeavor lipid particle delivery vehicles containing therapeutic agents (abstract), Jiang discloses wherein the a lipid nanoparticle composition (Col 3 ln 5-8, Col 4 ln 22, Col 5 ln 35-49, Col 11 ln 35-38, and Col 19 ln 58-60 ) , (i) at least one zwitterionic polymer-containing lipid in which a lipid moiety is covalently attached to a zwitterionic polymer (Col, 3, In 6-10; Col 6, In 6-10; Col 10, In 5-10; Col 10, In 54-63); (ii) at least one non-cationic lipid selected from charged and uncharged lipids, wherein the non-cationic lipid is not attached to a polymer (Col 4, In 6-9, "DOPG"); (iv) at least one therapeutic substance (Col 4, In 34-36), and iv wherein the therapeutic agent is a nucleic acid (column 11 lines 47-51)
Additionally in the same field of endeavor of lipid based nanoparticles for nucleic acid (siRNA) delivery (abstract) Yamazawa discloses a lipid nanoparticle composition
(abstract) comprising (iii) at least one cationic or ionizable lipid containing a tertiary amino group (DODAP) (pg. 68, Col 1, para 4, Figure 7), and (iv) at least one therapeutic substance (siRNA) (abstract and pg. 68, Col 1, para 4, Figures 3 and 7).
Regarding claim 17, Jiang discloses wherein said lipid moiety in component (i) is a diacylglyceride (Col 6, In 1-10; Col 10, In 22-23, and Co. 13, line 49 "phosphatidylglycerol" and “diglycerides”).
Regarding claim 18, Jiang discloses the composition of claim 1, wherein component (i) excludes a polyalkylene oxide (Col 10, In 6-23).
Regarding claims 19-21, Jiang discloses the composition of claim 1 wherein the zwitterionic polymer in component (i) is a betaine polymer that is selected from poly(carboxybetaine) poly (sulfobetaine), or poly(phosphobetaine) (Col 10, In 6-10 and claim 1).
Regarding claims 22 and 23 Jiang discloses (ii) at least one non-cationic lipid selected from charged and uncharged lipids, wherein the non-cationic lipid is not attached to a polymer (Col 4, In 6-9, "DOPG"); while Yonzewa discloses wherein the non-cationic lipid in component (ii) contains a zwitterionic moiety 1,2-distearoyl-sn glycero-3-phosphocholine (DSPC) (pg. 65, Col 2, para 2, "DSPC"). It would have been prima face obvious to one of ordinary skill in the art, before the effective filing date to include DPPC in the lipid nanoparticle as it improves lipid nanoparticle stability during formation and improves their stability in blood circulation as evidenced by Yonzewa (pg 65, Col 2, para 2).
Regarding claim 24, Jiang discloses wherein the non-cationic lipid is selected from Dioleoylphosphatidylglycerol, dipalmitoylphosphati dylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoyl-phosphatidylethanolamine (POPE), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phos phatidylethanolamine (DSPE), 16-O-monomethyl-phospho ethanolamine, 16-O-dimethyl-phosphoethanolamine, 18-1- trans-phosphoethanolamine, 1-stearoyl-2-oleoyl phosphatidyethanolamine (SOPE), or 1,2-dioleoyl-sn glycero-3-phophoethanolamine (transDOPE). (DOPG) (Col 4, In 8-19 and claim 9).
Regarding claim 25 Jiang discloses the composition of claim 1 wherein the component (ii) excludes a polyalkylene oxide segment (Col 10, In 14-22)
Regarding claim 26, Jiang discloses wherein the non-cationic lipid of component (ii) is a phospholipid selected from a phosphatidyl ethanolamine lipid (Col 10, In 14-22).
Regarding claim 29, Jiang discloses wherein the cationic lipid in component (iii) further comprises a quaternary group along with a functional group which is negatively charged under physiological conditions (Col 7, In 14-35).
As to Claim 30, Jiang discloses wherein the cationic lipid comprises the structure wherein R1 and R2 are each alkyl wherein the alkyl group can be is saturated and branched or unbranched and can be further substituted (Col 8, In 55-59; Col 7, In 25-40, "R6 and RS are each alkyl"), L is a covalent linker group between N and A, wherein the covalent linker group comprises CH2-COOCH2-(Col 7, In 45-46; Col 8, In 43-50), A-(X)n is a functional group that is negatively charged under certain pH conditions and can comprise (i) A(X)n as a carboxylic acid group, where A is COOH and n is O (Col 7, In 25-44, "A is carbon").
Regarding claim 32, Yonezawa discloses, wherein the cationic or ionizable lipid component in (iii) excludes polyalkylene oxide (pg. 68, Col 1, para 4, Figure 7, "DOTAP").
Regarding claim 33, Jiang discloses a lipid composition (abstract; Col 3, In 6-9; Col 15, In 44-48) further comprises cholesterol (column 14 lines 25 and 50).
Regarding claim 33, Yonzawa discloses a lipid composition comprises cholesterol (pg 66, para 1)).
Regarding claim 34, Jiang discloses a lipid composition (abstract; Col 3, In 6-9; Col 15, In 44-48) containing a lipid moiety attached to a quaternary amine group along with a functional group, wherein the functional group is negatively charged under physiological conditions (Col 3, In 6-9; Col 3, In 45-55; col 10, In 65 to col 11, In 6).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to combine Ambati, Jiang et al., and Yonzawa et al. to include (iii) at least one cationic or ionizable lipid containing a tertiary amino group (DODAP) (pg. 68, Col 1, para 4, Figure 7), and (iv) at least one therapeutic substance (siRNA) abstract and pg. 68, Col 1, para 4, Figures 3 and 7) as disclosed by Yonzawa in the lipid nanoparticle of Jiang as a matter of combining prior art elements according to known methods to yield predicable results, as instantly claimed, with a reasonable expectation of success. One of ordinary skill would be motivated to include (iii) at least one cationic or ionizable lipid containing a tertiary amino group as it is known to be used in the pharmaceutical arts as a part of a lipid nanoparticulate for deliver delivery of therapeutic nucleic acids (pg 65, col 3, para 2). One who would have practiced this invention would have had reasonable expectation of success because Jiang had already disclosed a lipid nanoparticle for delivery of a therapeutic agent wherein lipid particle comprises multiple functional groups, while Yonzawa provided guidance with respect to additional functional groups known to be used to be used as part of a nucleic acid lipid nanoparticle for delivery of a therapeutic.
It would have only required routine experimentation to include (iii) at least one cationic or ionizable lipid containing a tertiary amino group as required by the instantly claimed invention.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019) in view of Jiang et al. (Patent No.: US 8,617,592; Date of Patent: Dec. 31, 2013) and Yonezawa et al. (Advanced Drug Delivery Reviews, 154-155 (2020) 64-78) as applied to claims 1, 16, and 26 above and further in view of the combination of Jiang et al. (Pub. No.: WO 2019/183637; Pub. Date: Sep. 26, 2019) here-in-after referred to as Jiang WO and Li et al. (Sci. Adv. 2020; 6 May 29, 2020).
Regarding claim 27, the combination of Ambati et al., Jiang et al., and Yiang et al. remains as applied to claims 1, 16, and 26. While the combination teaches a method of delivery of a nucleic acid with a lipid vehicle loaded with nucleic acid as fully set forth above.
But the combination fails to disclose wherein the phospholipid is phosphatidyl serine lipid
However, in the same field of endeavor of particles comprising lipids (claims 1, 4, and 5) for drug delivery of therapeutic agents (page 2 lines 20-22) Jiang WO discloses wherein the nanoparticle the nanoparticle comprises phosphatidylserine (page 1 lines 19-27)
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to combine Ambati and Jiang WO to include a phosphatidylserine as part of a drug delivery vehicle as disclosed by Jiang WO in the lipid nanoparticle of Ambati as a matter of combining prior art elements according to known methods to yield predicable results, as instantly claimed, with a reasonable expectation of success. One of ordinary skill would be motivated to include the phosphatidyl serine lipid in order to help promote immune tolerance even in inflamed regions as evidenced by Jiang WO (page 1 lines 19-21). Wherein phosphatidylserine with the PS as a head group serves as an immunomodulatory signal under physiological conditions in order to promote clearance of apoptotic cells additionally the PS molecule is found to trigger the release of regulatory cytokines by directly or indirectly interacting with the PS receptor on the immune cells as disclosed by Li et al. (page 1 last paragraph through page 2 first paragraph). One who would have practiced this invention would have had reasonable expectation of success because Ambati had already disclosed a lipid nanoparticle for delivery of a therapeutic agent while Jiang WO and Li et al. provided guidance with respect to additional of phosphatidyl serine to lipid therapeutic agent delivery vehicles. It would have only required routine experimentation to include phosphatidyl serine as required by the instantly claimed invention.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
Claims 30 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Ambati et al. (Pub. No.: WO 2019/074884; Pub. Date: April 18, 2019) in view of Jiang et al. (Patent No.: US 8,617,592; Date of Patent: Dec. 31, 2013) and Yonezawa et al. (Advanced Drug Delivery Reviews, 154-155 (2020) 64-78) as applied to claims 1 and 16 above and further in view of Benenato, et al. (Pub. No.: WO 2018/232120; Pub. Date: Dec. 20, 2018).
Regarding claims 30 and 31, the combination of Ambati et al., Jiang et al., and Yonezawa et al. remains as applied to claims 1 and 16 as fully set forth above. While the combination teaches a method of delivery of a nucleic acid with a nanoparticle lipid vehicle loaded with nucleic acid to a subject with the with depleted macrophages wherein the lipid nanoparticle comprises i) at least one zwitterionic polymer-containing lipid in which a lipid moiety is covalently attached to a zwitterionic polymer; (ii) at least one non-cationic lipid selected from charged and uncharged lipids, wherein the non- cationic lipid is not attached to a polymer;(iii) at least one cationic or ionizable lipid. The combination of prior art references does not disclose the instantly claimed species of cationic or ionizable lipid.
However in the same field of endeavor of lipid nanoparticles delivery vehicles comprising a cationic and/or ionizable amino lipid and a targeting moiety (abstract, [002], [00550], and [00551]) for delivery of a nucleic acid to a subject ([0073]), Benenato discloses wherein the cationic or ionizable lipid is:
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[001067]
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date to combine Ambati, Jiang, Yonezawa et al., and Benenato et al. for the species of ionizable lipid to be 5-((8-(heptadecan-9-yloxy)-8-oxooct l)(8-(nonyloxy)-8-oxooctyl)amino)pentanoic acid as disclosed by Benenato in the lipid nanoparticle of the combination of Jiang and Yonezawa as a matter of combining prior art elements of lipid particle formation according to known methods to yield predicable results of a lipid particle nucleic acid delivery vehicle as instantly claimed, with a reasonable expectation of success. One of ordinary skill would be motivated to use the ionizable lipid species as it has little or no immunogenicity and increased therapeutic index as evidenced by Benenato ([00130] [0073]). One who would have practiced this invention would have had reasonable expectation of success because Ambati had already disclosed a lipid nanoparticle for delivery of a therapeutic agent while Jiang and Yonezawa provided guidance with respect to the genus of the ionizable lipid and Benenato provided guidance with respect to the species of the ionizable lipid. It would have only required routine experimentation to include specific ionizable lipid species as required by the instantly claimed invention.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill before the effective filing date.
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 1-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-62 of copending Application No. 18/268,472.
Although the confliction claims are not identical, they are not patentably distinct from each other because independent the claims application ‘472 recite the method of using lipid nanoparticles of identical compositions to deliver a therapeutic substance to a subject, wherein the therapeutic substance is a nucleic acid, and wherein the lipid nanoparticle comprises a targeting agent.
The dependent claims overlap or are identical in scope each reciting the same species making up the lipid nanoparticle, the target site, and the species of therapeutic agent.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No Claims are allowed.
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/ANNA R FALKOWITZ/
Primary Examiner, Art Unit 1600