DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communications filed 9-23-25.
Claims 1-7, 9, 11, 20, 21, 30, 33-35, 38, 39, 44-46 are pending in the instant application.
Election/Restrictions
Claims 35, 38, 39, 44-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9-23-25.
Applicant’s election without traverse of Group I, PEI, Polysorbate 40, claims 1-5, 7, 9, 11, 20, 21, 30, 33 and 34, in the reply filed on 9-23-25 is acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Please provide SEQ id Nos. for antisense molecules disclosed in the specification, figures and/or claims, where appropriate (see, e.g., claim 9, line 2; Specific deficiency –
This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because no sequence listing has been provided for this application. Antisense molecules are recited in the claim and specification, but no corresponding sequences or accompanying SEQ ID Nos. have been provided (see, e.g., claim 9, line 2).
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 33 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The claims encompass cells in an organism, including a human (perhaps inserting “isolated” before “cell” would be remedial).
Claim Rejections - 35 USC § 112
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 1-5, 7, 9, 11, 20, 21, 30, 33 and 34 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 20, line 2, recites the term “about”, rendering the claim vague and indefinite.
In claim 1, line 2, and in claim 34, lines 2-3, the phrase “amount sufficient to charge neutralize” is vague and unclear, rendering the claim indefinite. The neutralization will depend on many factors, including the molecular weight and molecular compositions of the cations, and molecular weight of the therapeutic nucleic acid of acids (See, e.g., pages 17-18 of the specification).
Appropriate clarifications/corrections are required.
Claim 21 contains the trademark/trade name oleoyl polyoxyl-6 glyceride/oleoyl macrogol-6 glyceride, (LABRAFIL®), Pluronic F127, polysorbate 40 (TWEEN® 40), polysorbate 80 (TWEEN® 80).
Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe (LABRAFIL®), Pluronic F127, polysorbate 40 (TWEEN® 40), polysorbate 80 (TWEEN® 80) and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-5, 11, 34 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Suk et al (US 2017/0246320).
Suk et al (US 2017/0246320) teach gene carrier compositions comprising cationic polymers comprising polyethyleneimine (PEI) backbones and PEI side chains, with cationic polymers between 5000-100,000 Daltons, and further comprising mucolytic, mucus resistant and mucus diffusive polymers, which polymers are optionally neutrally charged. Suk teaches delivery of mucolytic PEI DNA cationic nanoparticles to treat cystic fibrosis (CF) patients (see esp. the Abstract, ¶¶ 0007, 0013, Figures 1-7, ¶¶ 0030-0036, 0069-0071, 0121, 0194-0252, claims 1-18).
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.
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.
Claim(s) 1-5, 7, 9, 11, 20, 21, 30, 33, 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Suk et al (US 2017/0246320) in view of Frederick et al (US 2023/0081530), and Shariter et al (US 2020/0306191), the combination further in view of Fyfe, M. (2016/0096805).
The claims are drawn to compositions and complexes produced by combining one to three mucopenetrating substances, a therapeutic nucleic acid, and a cationic linear or branched polymer in an amount sufficient to charge neutralize the therapeutic nucleic acid, which mucopenetrating substances are non-ionic emulsifiers and have mucolytic activity, which therapeutic nucleic acid and cationic polymer form a complex through ionic interactions, which cationic polymer comprises a cationic lipid, which therapeutic nucleic acid is optionally an antisense oligonucleotide (ASO), optionally comprising mongersen (GED-0301), which cationic polymer optionally comprises polyallylamine (PALL), polylysine (PLL), or polyethyleneimine (PEI), which concentration of the cationic polymer in the composition is 10-30 mg/ml, which non-ionic emulsifier optionally comprises oleoyl polyoxyl-6 glyceride/oleoyl macrogol-6 glyceride (LABRAFIL®), Pluronic F127, polysorbate 40 (TWEEN® 40), polysorbate 80 (TWEEN® 80), or Kolliphor P188, which cationic polymer and therapeutic nucleic acid are present at a ratio of at least 1:1, 5:1, or 10:1 cationic polymer:therapeutic nucleic acid.
Suk et al (US 2017/0246320) teach gene carrier compositions comprising cationic polymers comprising PEI backbones and PEI side chains, with cationic polymers between 5000-100,000 Daltons, and further comprising mucolytic, mucus resistant and mucus diffusive polymers optionally neutrally charged. Suk teaches delivery of mucolytic PEI DNA cationic nanoparticles to treat cystic fibrosis (CF) patients (see esp. the Abstract, ¶¶ 0007, 0013, Figures 1-7, ¶¶ 0030-0036, 0069-0071, 0121, 0194-0252, claims 1-18).
The primary reference does not teach the emulsifiers recited in claim 21, or the ratio of cationic polymers to nucleic acids of 1:1, 5:1 or 10:1, compositions comprising GED-0301.
Frederick et al (US 2023/0081530) teach compositions comprising ionizable lipids and nucleic acids, non-cationic helper lipids, phospholipids, PEG lipids (¶¶ 0461-0777, 1149-1220), and further comprising emulsifying agents and self-assembled DNA ¶¶ 1545-1549 1630-1631) Frederick teaches nucleic acid delivery compositions comprising cations, and formulations with multiple nucleic acids, optionally comprising siRNA, shRNA, miRNA and/or mRNA (¶¶ 1545-1549). Frederick teaches cationic polymer compositions cationic polymer:nucleic acid ratios of at least 1:1-10:1, and cationic polymer concentrations of approximately between 10-30 mg/ml and compositions comprising polysorbates as emulsifiers (see Tables 36-39, ¶¶ 132-138, 142, 0216, 1438-1447, 1523-1524, 1549).
Shariter et al (US 2020/0306191) teach compositions comprising nucleic acid lipid nanoparticles encapsulating mRNA, and further comprising one or more surfactants optionally comprising polysorbates (¶ 0314), and cationic phospholipids neutralizing negatively charged lipids and phospholipids (¶ 0327), antisense and other therapeutic molecules ¶¶ 0361-0364). Shariter also teaches compositions comprising emulsifying agents, cation surfactants, nucleic acid polymers, mucolytic agents for nucleic acid delivery (¶¶ 0568-0569), and which compositions further comprise the polymers PLGA, PLLA, PLL and PLA (¶¶ 0509-0511 0514, 0515 – 0519, 0548, 0606, 0616, 0618).
Fyfe, M. (2016/0096805) teach therapeutic compositions comprising the antisense molecule, mongersen (GED0301), for treating gastrointestinal disorders (see esp. ¶ 0127).
It would have been obvious to provide therapeutic compositions comprising neutrally charged combinations of nucleic acids, cationic polymers comprising PEI backbones and PEI side chains, which cationic polymers are between 5000-100,000 Daltons, and further comprising mucolytic, mucus resistant and mucus diffusive polymers optionally neutrally charged because the prior art taught compositions with these components, as shown in the teachings of Suk. What’s more, Frederick teaches nucleic acid delivery compositions comprising cations, and formulations with multiple nucleic acids, optionally comprising siRNA, shRNA, miRNA and/or mRNA, and emulsifiers comprising polysorbates. And Shariter teaches compositions comprising emulsifying agents, cation surfactants, nucleic acid polymers, mucolytic agents for nucleic acid delivery. One would have been motivated to combine the components claimed because the prior art taught the effective delivery of therapeutic agents using the instant compositions claimed. One would have reasonably expected that antisense, including mongersen (GED0301), would be successfully delivered to a subject for treating digestive disorders in combination with the cationic, lipid, and emulsifier agents, relying on the combined teachings of Suk, Frederick, Shariter and Fyfe.
For these and the aforementioned reasons, the instant invention would have been obvious to one of ordinary skill before the effective filing date of the claimed invention.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
11-13-25
/JANE J ZARA/Primary Examiner, Art Unit 1637