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 .
Detailed Action
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 13 September 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. See attached copy of PTO-1449.
Status of Application
2. The instant application is a national stage entry of PCT/US2022/028482 filed 10 May 2022. Claims 1-16, 20, 23, 25, 27, 29-31, and 33 are currently pending. Claims 17-19, 21-22, 24, 26, 28, and 32 are cancelled. Claims 1-16, 20, 23, 25, 27, 29-31, and 33 are examined on the merits within.
Claim Rejections – 35 U.S.C. 112(b)
3. 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.
4. Claims 1-16, 20, 23, 25, 27, 29-31, and 33 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.
5. Claim 1 recites “wherein the ionizable amino lipid is Compound II or its N-oxide, or a salt or isomer thereof, or Compound A or its N-oxide, or a salt or isomer thereof”. Compound II and Compound A are not described in the claims. Where possible, claims are to be complete in themselves. Incorporation by reference from the specification "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.” Ex parte Fressola, 27USPQ2d 1608, 1609 (Bd, Pat. App. & Inter. 1993) (citations omitted). In the instant case, there is a more practical way to define the invention, by incorporating the structures of the compounds into the claim. Claim 6 is included in this rejection for the same deficiencies regarding not claiming the actual structure, but instead referencing a structure found in the specification.
6. Claim 3 recites the limitation "the human interferon beta gene" in line 2. There is insufficient antecedent basis for this limitation in the claim.
7. Claim 16 recites the limitation "the human TTR promoter or the human AAT promoter" and “the human ApoE HCR1 enhancer or the human TTR enhancer” in lines 2-4. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections – 35 U.S.C. 103
8. 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.
9. Claim(s) 1, 4-7, 9-16, 20, 23, 25, 27, 29-31, and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. (WO2019/226650) in view of Stanton et al. (WO2020/181168).
Regarding instant claims 1, 7, and 23, Dimitrov et al. teach a pharmaceutical composition comprising a DNA sequence formulated in a lipid nanoparticle comprising an ionizable cationic lipid, a phospholipid, a structural lipid, and a PEG lipid. See abstract. In some embodiments, the ionizable cationic lipid is
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(Compound II), or a salt thereof. See page 3. Compound II is the same structure of Compound II in claim 1. The DNA may be plasmid or close-ended linear duplex DNA. See page 5.
Regarding instant claim 4, the phospholipid is DSPC. See page 4.
Regarding instant claim 5, the structural lipid is cholesterol. See page 5.
Regarding instant claim 6, the PEG-lipid is compound:
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See page 56.
Regarding instant claim 10, Table 2 comprises formulations having 45% compound, 15% phospholipid, 38.5% cholesterol, and 1.5% PEG-lipid.
Regarding instant claim 25, the plasmid may be bacterial plasmid. See page 5.
Dimitrov et al. do not teach a DNA sequence with a tissue specific regulatory region, a nucleotide sequence encoding a polypeptide, a terminator of transcription or a poly(A) signal.
Stanton et al. teach delivering capsid-free DNA vectors to a target cell to reduce or inhibit an immune response. See abstract. FIG. 1C illustrates an exemplary structure of a ceDNA vector for expression of a transgene as disclosed herein comprising asymmetric ITRs, with an expression cassette containing an enhancer/promoter, the transgene, a post transcriptional element (WPRE), and a polyA signal. See paragraph [0031]. The DNA vector may include a tissue specific promoter such as a liver specific promoter. See paragraph [00232]. Both tissue specific enhancers and promoters can be used, including ApoE and AAT. See paragraph [00159] and Tables 7-8. Delivery to the liver can be achieved using endogenous ApoE specific targeting of the composition comprising a ceDNA vector to hepatocytes via a low density lipoprotein receptor on the surface of the hepatocyte. See paragraph [00232]. In some embodiments, the expression of the transgene or therapeutic protein from the ceDNA vector is controlled such that the transgene or therapeutic protein is expressed every 2 weeks or every 4 weeks for a period of time. In certain embodiments, the period of time is 6 months, one year, eighteen months, two years, five years, ten years, 15 years, 20 years, or the lifetime of the patient. See paragraph [00368]. The ceDNA vector selected comprises a nucleotide sequence encoding a desired transgene or therapeutic protein useful for treating a disease. In particular, the ceDNA vector may comprise a desired transgene or therapeutic protein sequence operably linked to control elements capable of directing transcription of a desired transgene or therapeutic protein encoded by the exogenous DNA sequence when introduced into the subject. The ceDNA vector can be administered via any suitable route as provided above, and elsewhere herein. See paragraph ][00307]. Generally, lipid nanoparticles comprise an ionizable amino lipid, a phosphatidylcholine (1,2-distearoyl-sn-glycero-3-phosphocholine, DSPC), cholesterol and a coat lipid (polyethylene glycol-dimyristolglycerol, PEG-DMG). See paragraph [00265]. The expression levels of secreted protein encoded by ceDNA were determined. See Example 13. A pre-mixed custom mouse cytokine 1-plex kit was used for assaying INF-beta. See Example 14.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the DNA of Dimitrov et al. to additionally comprise a tissue specific regulatory region, a nucleotide sequence encoding a polypeptide, a terminator of transcription and a poly(A) signal because this is a known method of modification of DNA vectors to achieve specific site directed therapy. One would have been motivated with a reasonable expectation of success to provide a more effective site specific delivery of therapeutic.
10. Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. (WO2019/226650) in view of Stanton et al. (WO2020/181168) as applied to claims 1, 4-7, 9-16, 20, 23, 25, 27, 29-31, and 33 above and further in view of Jacobs et al. (Gene Therapy, 2008).
Dimitrov et al. and Stanton et al. do not teach a scaffold matrix attachment region.
Jacobs et al. teach expression cassettes for hepatocyte-directed transfer have been improved by using new promoter-enhancer combinations, inclusion of introns and inclusion of additional transcriptional sequences like scaffold matrix-attached regions (SMAR) and hepatic control regions (HCR). See Introduction. Examples include SMAR from the 5′ region of the human interferon-β gene in the construct E4.AT.gA-I.SMAR. See Results.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add a scaffold matrix attached region to the DNA vector of Stanton et al. to improve the expression cassette. One would have been motivated, with a reasonable expectation of success, because Jacobs et al. specifically teach the addition of human interferon beta gene scaffold matrix attached regions successfully combined with promoters/enhancers to improve expression cassettes.
11. Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dimitrov et al. (WO2019/226650) in view of Stanton et al. (WO2020/181168) as applied to claims 1, 4-7, 9-16, 20, 23, 25, 27, 29-31, and 33 above and further in view of Benenato et al. (WO2020/061367).
Dimitrov et al. and Stanton et al. do not teach Compound A.
Benenato et al. teach nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. See abstract. Compound 301:
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meets the formula of Compound A. See paragraph [00281]. Within the same Table, Compound 32:
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meets the limitations of the instantly claimed Compound II.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to substitute one lipid for another to yield predictable results because Benenato et al. teach the equivalency of compound 301 and compound 32 in nanoparticle compositions including a novel lipid, phospholipids, structural lipids, and PEG lipids.
Correspondence
12. No claims are allowed at this time.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615