DETAILED ACTION
Status of Application
Preliminary amendments to the claims, filed 10/01/2024, are acknowledged. Claims 1-12, 14-15, 17-24 are pending in this action. Claims 13, 16, 25-29 have been cancelled. Claims 4-11, 14, 19, 21-23 have been amended. Claims 1-12, 14-15, 17-24 are currently under consideration.
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 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
This application is a 371 of PCT/US2023/065720, filed April 13, 2023, which claims benefit of provisional U.S. Application No. 63/364,859, filed May 17, 2022, and U.S. Application No. 63/330,972, filed April 14, 2022.
Inventorship
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.
Specification
The lengthy specification (71 pages, exclusive of claims) has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. MPEP 608.01. The specification is objected to because of the following informalities:
The specification comprises multiple acronyms without proper definition (e.g., Pages 1, 4-7, 15, 32). The acronym should be given once in parentheses after the first use of the full term, and then the acronym used alone thereafter if needed. Appropriate correction is required.
The specification comprises references on publications (e.g., Pages 9, 12, 14-15, 27-28, 36-40, 46-47) and a foreign application (Pages 28, 33, 35-36). The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g). Clarification is required.
The use of the trademarks/trade names has been noted in this application, e.g., Pluronic P85 (Page 14; see bioz.com), PCRTM (Page 38). It should be capitalized wherever it appears and be accompanied by the generic terminology. Although the use of trademarks/trade names is permissible in patent applications, the proprietary nature of the trademarks/trade names should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks. The use of language such as “the product X (a descriptive name) commonly known as Y (trademark)” is not permissible since such language does not bring out the fact that the latter is a trademark. Language such as “the product X (a descriptive name) sold under the trademark Y” is permissible. MPEP §608.01(v). Further, it is noted that the trademarks/trade names are used to identify a source of goods, and not the goods themselves. The formula or characteristics of the product may change from time to time and yet it may continue to be sold under the same trademark/trade name. Thus, a trademark/trade name does not identify or describe the goods associated with the trademark/trade name. Appropriate correction is required.
The disclosure contains an embedded hyperlink and/or other form of browser-executable code (\Page 27). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. MPEP 608.01. Appropriate correction is required
Information Disclosure Statement
The information disclosure statement, filed 06/11/2025, is acknowledged and has been considered. Please see the attached initialed PTO-1449.
Foreign language references listed in the information disclosure statement, for which no English translation has been provided, have not been considered. If an English abstract has been provided or available for a foreign language document then only the English abstract has been considered.
The information disclosure statement does not include Certificate Statement and Privacy Act Statement (MPEP 609), and/or does not have a signature of the applicant or representative that is required in accordance with CFR 1.33.
Claim Objections
Claims 1, 5, 7-8, 10, 15, 17-18, 22 are objected to because of the following informalities:
Claim 1 comprises the typographic error “range of about 1 mol% to” that needs to be corrected to “range of from about 1 mol% to”. Similar is applied to other range limitations recited in claim 1, as well as to claims 7, 8, 10, 15.
Claim 1 recites the limitation “lipid is in a concentration range” that needs to be corrected to “lipid is present in a concentration range” for clarity (see other concentration limitations recited in claim 1).
The acronym “DOPE” recited in claim 5 should be removed, because said acronym is not used in subsequent claims.
Claim 7 comprises the typographic error “the ratio” that needs to be corrected to “a ratio”.
Claim 8 recites the limitation “the molar (mol) ratio of a:b:c:d” that needs to be corrected to “a molar ratio a:b:c:d” or clarified.
The acronym “TEM” recited in claim 10 should be removed, because said acronym is not used in subsequent claims.
Claims 17 and 18 comprise acronyms “TAL”, “TTR” and “PCSK9”. The acronym should be given once in parenthesis after the first use of the full term, and then the acronym is used alone thereafter if needed.
Claim 22 comprises the typographic error “300 nM sucrose” that needs to be corrected to “300 nmol of sucrose” or clarified.
Appropriate correction is required.
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 1-12, 14-15, 17-24 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 pre-AIA the applicant regards as the invention.
Claim 1 recites the term "about" that is a relative term, which renders the claim indefinite. This term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, but teaches that the term “about” allows a variability of numerical limitation by ±25%, ±20%, ±10%, ±5%, ±1%, or ±0.1% (Page 8). Similar is applied to claims 7, 8, 10, 15, 22. Clarification is required.
Claim 4 recites the limitation “the neutral phospholipid comprises dioleoylphosphatidylethanolamine” that is not reasonably clear. Does this limitation imply that said neutral phospholipid is a mixture, i.e., may include other compounds even in large amounts (i.e., comprising)? Similar is applied to claim 6 regarding the limitation “PEG-lipid comprises”. Clarification is required.
Claim 5 recites the limitation “cholesteryl derivate” that is unclear. Clarification is required.
Claim 7 recites the limitation “the ratio of ionizable lipid to nucleic acid in an LNP is about 5:1 to about 10:1, based on weight percentage of the lipids” that is not reasonably clear. Does this limitation disclose a weight ratio of ionizable lipid to nucleic acid? Clarification is required.
Claim 10 recites the limitation “the average diameter of the LNPs comprises about 50 nm to about 150 nm” that is unclear. This limitation was interpreted as best understood as “the average diameter of the LNPs is in the range of from 50 nm to 150 nm”. Clarification is required.
Claim 15 (dependent on claims 14, 11) recites the limitation “the ratio of mRNA to sgRNA is about 1:5 to 5:1 mRNA to sgRNA based on molar percentage” that is unclear. First, it is noted that claims 11 and/or 14 do not disclosed the use/presence of mRNA. Therefore, it is unclear how claim 15 narrows the scope of the claims upon which it depends. Second, the numerical limitation is not clearly delineated. This limitation was interpreted as best understood as “a molar ratio of mRNA to sgRNA is from 1:5 to 5:1”. Clarification is required.
Claim 20 (dependent on claims 19, 1) recites the limitation “therapeutic transgene is associated with a liver enzyme disorder, a lysosomal storage disorder, a glycogen storage disease or deficiency, a urea cycle disorder, or a lipid disorder” that is not reasonably clear. To this point, it is noted that “Claiming a result without reciting what materials produce that result is the epitome of an indefinite claim. Such a claim fails to delineate with any reasonable certainty the requirements of the formulation.” See Forest Labs., Inc. v. Teva Pharms. USA, Inc. 2017 U.S. App. LEXIS 24877. Further, it is noted that the invention should be explained in such a way as to describe what the invention is, not what the invention does. In the present case, given that "Claim scope is not limited by claim language that does not limit a claim to a particular structure” (MPEP 2111.04 and 2173.05(g)), one of ordinary skill in the art would not be reasonably appraised of the scope of the invention. Similar is applied to claim 21 regarding the limitation “promoter operably linked to a sequence encoding a therapeutic gene product.” Clarification is required.
Claims 2-3, 9, 11-12, 14, 17-19, 23-24 are rejected as being dependent on rejected independent claim 1 and failing to cure the defect.
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.
Claims 1-12, 14-15, 17-24 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al., US 2022/0378938 A1 (priority to CN 113402404 A filed 09/17/2021, hereinafter referred to as Huang).
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Huang teaches lipid nanoparticles (LPNs) comprising a lipid carrier and a nucleic acid and their use for gene therapy (Abstract; Para. 0007-0010). To this point, Huang teaches that said LPNs have a particle size of 30-500 nm (Claims 12, 17; Para. 0060 as applied to claims 1, 10) and may include:
(i) ionizable lipid compound (shown on the right) having a structure that is a derivative of the compounds of Formular (IA) and/or Formular (IB) providing a modification of end groups (i.e., compound 33; Para. 0041 as applied to claims 1-3);
(ii) at least one neutral lipid, e.g., DOPE, i.e., dioleoylphosphatidylethanolamine (Claims 7, 14; Para. 0047 as applied to claims 1, 4);
(iii) at least one polyethylene glycol (PEG) lipid, e.g., PEG-C14 (Claim 7; Para. 0048 as applied to claim 1);
(iv) cholesterol (Para. 0141, 0146, 0150-152 as applied to claims 1, 5);
(v) at least one nucleic acid selected from the group consisting of a DNA, an siRNA, an mRNA, a dsRNA (Claims 9, 16; Para. 0055 as applied to claims 1, 9).
Huang specifically teaches preparation of said LNPs comprising compound 33, cholesterol, DOPE and PEG-DMG (i.e., PEG-lipid) in a molar ratio of 35:46.5:16:2.5 (Para. 0141 as applied to claims 1, 8).
Huang further teaches the use of sucrose as a cryopreservation protective agent (Para. 0150-0152 as applied to claim 22).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare the LNPs as taught by Huang to be used for in vivo delivery of nucleic acid drugs. One would do so with expectation of beneficial results, because Huang teaches LNPs with high encapsulation efficiency for nucleic acid drugs, providing enhanced in-vivo delivery efficiency of nucleic acid drugs in different organs. Claims 6-7, 11-12, 14, 17-21, 23-24 are rejected as being dependent on rejected claim 1. Applicant is advised to clarify the claim language, the structure of the claimed lipid nanoparticles and/or compounds included therein and clearly point out the patentable novelty, which the applicant thinks the claims present in view of the state of the art disclosed by the references cited, to place the application in condition for allowance.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-12, 14-15, 17-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-15, 26 of copending Application No. 18/856,855.
Although the conflicting claims are not identical, they are not patentably distinct from each other, because the subject matter claimed in the instant application is fully disclosed in the referenced copending applications and would be covered by any patent granted on that copending application since the referenced copending application and the instant application are claiming common subject matter, as follows: A biodegradable lipid nanoparticle comprising: (a) at least one compound of Formular (IA) and/or Formular (IB) (here as 306-HB6b(B1) and 113-HB7b2, respectively); (b) at least one neutral phospholipid present in a concentration range of 5-45 mol%; (c) at least one cholesterol lipid present in a concentration range of 5-55 mol%; (d) at least one polyethylene glycol-lipid present in a concentration range of 0.5-12.5 mol%; and (e) at least one encapsulated nucleic acid. Therefore, the claimed invention is directed to the same invention or is an obvious variation of the invention claimed in said copending application. This is a provisional obviousness-type double patenting rejection, because the conflicting claims have not in fact been patented.
Correspondence
No claim is allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA V. TCHERKASSKAYA whose telephone number is (571)270-3672. The examiner can normally be reached 9 am - 6 pm, Monday - Friday.
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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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