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 . Claims included in prosecution are claims 1, 3, and 120-137.
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 120 is 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 120 recites “non-cationic lipid. The instant specification discloses that phospholipids are a subset of “non-cationic lipids”. Therefore it would appear that the scope of the claim in regards to the non-cationic lipid is being broadened. Therefore, the claim is not further limiting in this regard. 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.
For the purposes of compact prosecution, the term “non-cationic lipid” will be interpreted as the phospholipid recited in claim 1 from which claim 120 depends.
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.
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.
1. Claim(s) 1, 3, and 120-137 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. (US 2020/0129445, Apr. 30, 2020) (hereinafter Patel) in view of Hahn et al. (US 2015/0297749, Oct. 22, 2015) (hereinafter Hahn) and Ahmad et al. (WO 2020/252375, Dec. 17, 2020) (hereinafter Ahmad).
Patel discloses nanoparticle compositions include an ionizable lipid, a phospholipid, a first sterol or a tocopherol, further including therapeutic and/or prophylactics such as RNA which are useful in the delivery of therapeutic and/or prophylactics to mammalian cells (Abstract). In one aspect, the composition provides a nanoparticle composition comprising a lipid component comprising: an ionizable lipid (satisfies component (i)), a phospholipid (satisfies component (ii)), and a first sterol or a tocopherol (satisfies component (iii)) (¶ [0006-0009]). In certain embodiments, the ionizable lipid is a compound of Formula (I) (¶ [0018]). Cholesterol is a suitable first sterol (¶ [0093]). Suitable compounds of formula (I) (i.e., ionizable lipid) include compound 18 and compound 236 (¶ [0274-0276]). The specific delivery of the therapeutic results in at least 1.5 fold more or up to at least 10 fold more delivery of the therapeutic compared to systemic administration (¶ [0292]). A nanoparticle composition may include one or more cationic and/or ionizable lipids (e.g., lipids that may have a positive or partial positive charge at physiological pH) in addition to a lipid according to Formula (I) (¶ [0336]). Suitable cationic lipids include spermine cholesterylcarbamate (GL-67) (satisfies claim 122) (¶ [0337]). The lipid component of a nanoparticle composition may include one or more PEG or PEG-modified lipids (satisfies component (iv)). Such species may be alternately referred to as PEGylated lipids. Suitable PEG lipids include PEG-DMG (¶ [0338]). Phospholipids useful in the compositions include 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) (¶ [0344). The therapeutic agent may be encapsulated within the nanoparticle (¶ [0346]). Exemplary polynucleotides for use include one or more of deoxyribonucleic acid (DNA), ribonucleic acid
(RNA) including messenger mRNA (mRNA), siRNAs etc. (¶ [0350]). The amount of a therapeutic and/or prophylactic in a nanoparticle composition may depend on the size, composition, desired target and/or application, or other properties of the nanoparticle composition as well as on the properties of the therapeutic and/or prophylactic. For example, the amount of an RNA useful in a nanoparticle composition may depend on the size, sequence, and other characteristics of the RNA. The relative amounts of a therapeutic and/or prophylactic and other elements ( e.g., lipids) in a nanoparticle composition may also vary. In some embodiments, the wt/wt ratio of the lipid component to a therapeutic and/or prophylactic in a nanoparticle composition may be from about 5:1 to about 60:1 (satisfies claim 123) (¶ [0478]). The composition comprises a compound according to formula (I) in an amount of about 30 mol % to about 60 mol %, about 5 mol % to about 25 mol % phospholipid, about 30 mol % to about 40 mol % structural lipid, and about 0 mol % to about 10 mol % of PEG lipid, wherein the structural lipid may be cholesterol (¶ [0475]). In some embodiments, the nanoparticle has a zeta potential of from about +5 mV to about +20 mV (satisfies zeta potential of claim 1) (¶ [0484]). Targeted cells include hepatocytes, epithelial cells, and lung cells (¶ [0522]). In Table 2, PEG(2k)-DMG was used in exemplary embodiments (¶ [0555]).
Patel differs from the instant claims insofar as not disclosing wherein the cationic lipid is disposed on the surface of the nanoparticle.
However, Hahn discloses a low density lipoprotein-like (LDL-like) nanoparticle consisting of a core-shell structure comprising a solid lipid core; and an outer shell containing cationic lipids (¶ [0022]). The shell is bonded to the top layer of the core by hydrophobic interaction, and includes exposed cationic lipids that can interact electrostatically with drugs, particularly nucleic acid genes. The nanoparticles of the present invention may bind with drugs, particularly nucleic acid genes by electrostatic interaction through the exposed cationic lipids of the shell, thus easily forming a complex, and it may be usefully used as a composition for intracellular delivery of drugs, particularly nucleic acid genes (¶ [0033]). The nucleic acid may be at least one selected from the group consisting of small interfering RNA (siRNA), ribosomal ribonucleic acid (rRNA), ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and messenger ribonucleic acid (mRNA) (¶ [0061]).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant claims, to have modified the nanoparticle of Patel to contain the cationic lipid on the surface of the nanoparticle, motivated by the desire to utilize the electrostatic interactions that the cationic lipid would have with the nucleic acid cargo to achieve the nanoparticle/drug complex and intracellular drug delivery taught by Hahn.
The combined teachings of Patel and Hahn do not disclose wherein the amount of cationic lipid is 2-10 mol%.
However, Ahmad disclose nanoparticles which comprise ionizable lipids and/or cationic lipids, and phospholipids for use in the delivery of therapeutics, particularly nucleic acid therapeutics, to epithelial cells (Abstract). Suitable cationic lipids include GL-67 (¶ [0004]). In an embodiment, the delivery vehicle comprises DSPC (¶ [0010]). In an embodiment, the delivery vehicle comprises a pegylated lipid such as DMG-PEG (¶ [0011]). The term "about" and its grammatical equivalents in relation to a reference numerical value and its grammatical equivalents as used herein can include a range of values plus or minus 10% from that value (¶ [0045-0046]). Cationic lipids such as GL-67 can be included in the particle at about 10 mole %, 8 mole %, 6 mole %, 4 mole %, 2 mole %, or 0 mole % (¶ [0100]). Multivalent cationic lipids can be used to create enough positive to negative charge ratio to provide the system with a balance of attraction and repulsion thereby generating a delivery vehicle containing a charge separation (¶ [0105]). In exemplary delivery vehicles containing encapsulated nucleic acids, the cationic lipid : nucleotide molar ratio was maintained at about 16 (¶ [0194]).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant claims, to have modified the nanoparticle of Patel to contain the cationic lipid in a concentration from 0-10 mole % and a cationic lipid : nucleotide molar ratio of about 16 since these are known and effective concentrations/ratios of GL-67 for use in lipid nanoparticles comprising such a cationic lipid along with ionizable lipids, phospholipids, and pegylated lipids for the delivery of nucleic acids as taught by Ahmad.
Regarding the molar ratios recited in instant claims 1, 126-127, 129, 131, 133, 135, and 137, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). As discussed above, the nanoparticle of Patel in view of Hahn and Ahmad comprises a compound according to formula (I) in an amount of about 30 mol % to about 60 mol %, about 5 mol % to about 25 mol % phospholipid, about 30 mol % to about 40 mol % structural lipid, and about 0 mol % to about 10 mol % of PEG lipid, and between 0-10 mol % GL-67. Accordingly, because the molar ratios recited in the instant claims overlap with and/or lie inside the ranges disclosed by Patel in view of Hahn and Ahmad, the ranges disclosed by Patel in view of Hahn and Ahmad meet the instantly recited limitations.
Regarding claim 3, the nanoparticle of Patel in view of Hahn and Ahmad comprises substantially the same lipid components where it comprises compounds 18 or 236, DSPC, cholesterol, PEG-DMG, and GL-67, and further comprises substantially the same actives where it comprises polynucleotides in molar ratios that overlap with the concentrations instantly claimed. Accordingly, it would be reasonable for one of ordinary skill in the art to conclude that the nanoparticle of Patel in view of Hahn and Ahmad would result in a cellular accumulation and cellular expression such as the one instantly claimed.
Therefore, the combined teachings of Patel, Hahn, and Ahmad render obvious claims 1, 3, and 120-137.
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.
1. Claims 1, 3, and 120-137 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 3-17 of copending Application No. 18/040,485 in view of Patel et al. (US 2020/0129445, Apr. 30, 2020) (hereinafter Patel) and Ahmad et al. (WO 2020/252375, Dec. 17, 2020) (hereinafter Ahmad).
The pending claims differ from the copending claims insofar as reciting wherein the nanoparticle comprises a molar ratio of: 20-60% ionizable cationic lipid, 5-25% phospholipid, 25-55% sterol, 0.5-15% PEG modified lipid, and 2-10% cationic agent.
Patel discloses nanoparticle compositions include an ionizable lipid, a phospholipid, a first sterol or a tocopherol, further including therapeutic and/or prophylactics such as RNA which are useful in the delivery of therapeutic and/or prophylactics to mammalian cells (Abstract). A nanoparticle composition may include one or more cationic and/or ionizable lipids (¶ [0336]). The lipid component of a nanoparticle composition may include one or more PEG or PEG-modified lipids (satisfies component (iv)). (¶ [0344). The therapeutic agent may be encapsulated within the nanoparticle (¶ [0346]). The composition comprises a compound according to formula (I) in an amount of about 30 mol % to about 60 mol %, about 5 mol % to about 25 mol % phospholipid, about 30 mol % to about 40 mol % structural lipid, and about 0 mol % to about 10 mol % of PEG lipid, wherein the structural lipid may be cholesterol (¶ [0475]). In some embodiments, the nanoparticle has a zeta potential of from about +5 mV to about +20 mV (¶ [0484]).
Patel differs insofar as not disclosing wherein the amount of cationic lipid is 2-10 mol%.
However, Ahmad disclose nanoparticles which comprise ionizable lipids and/or cationic lipids, and phospholipids for use in the delivery of therapeutics, particularly nucleic acid therapeutics, to epithelial cells (Abstract). Suitable cationic lipids include GL-67 (¶ [0004]). In an embodiment, the delivery vehicle comprises DSPC (¶ [0010]). In an embodiment, the delivery vehicle comprises a pegylated lipid such as DMG-PEG (¶ [0011Cationic lipids such as GL-67 can be included in the particle at about 10 mole %, 8 mole %, 6 mole %, 4 mole %, 2 mole %, or 0 mole % (¶ [0100]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated the ionizable cationic lipid, phospholipid, sterol, PEG modified lipid, and cationic agent into the pending claims at a molar ratio of 20-60% ionizable cationic lipid, 5-25% phospholipid, 25-55% sterol, 0.5-15% PEG modified lipid, and 2-10% cationic agent since these are known and effective concentrations for use in lipid nanoparticles comprising such components as taught by Patel and Ahmad.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1, 3, and 120-137 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.A./Examiner, Art Unit 1612
/LEZAH ROBERTS/Primary Examiner, Art Unit 1612
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