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 . 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.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15 and 19-26, in the reply filed on 01/16/2026, is acknowledged.
Applicant’s election of, the following species, in the reply filed on 01/16/2026, is acknowledged:
1. (ApoE)/hAAT (species of liver specific promoter or liver specific promoter/enhancer)
2. emactuzumab (species of antibody or antibody binding fragment)
3. clondronate (species of bisphosphonate)
4. lipid particle (species of non-viral delivery particle)
5. plasmid (species of dsDNA)
6. therapeutic protein (species of encoded component)
7.
PNG
media_image1.png
160
515
media_image1.png
Greyscale
(species of lipid)
Claims 22, 24 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/16/2026.
Claim Rejections - 35 USC § 112 –
Indefiniteness, Lack of Antecedent
Basis and Broad to Narrow Limitations
Claims 5, 20-21 and 25 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.
Regarding broad to narrow limitations, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 5 recites the broad recitations “transthyretin”, “human alpha 1-antitrypsin”, “alpha-fetoprotein”, “thyroxin binding globulin” and “apolipoprotein E”, and the claim also recites “(TTR)”, (hAAT)”, “(AFP)”, “(TBG)” and “(ApoE)” which are the narrower statements of the range/limitations. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 21 recites the broad recitation “closed-ended linear duplex DNA”, and the claim also recites “(CELiD/ceDNA/doggybone DNA)” which is the narrower statement of the range/limitation.
In the present instance, claim 25 recites the broad recitation “lipid nanoparticle”, and the claim also recites “(LNP)” which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The Applicant is encouraged to remove the parentheses, rather than the abbreviations, from the claims.
Regarding lack of antecedent basis, claim 20 recites the limitation "particle" in line two. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-11, 15, 19-21, 23 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Lacroix-Desmazes (WO 2020/016318 A1), in view of Qu et al (WO 2018/226887 A1), further in view of Dimitrov et al (US 2021/0346306 A1) and further in view of Cassier et al (European Journal of Cancer, 141, 2020, 162-170).
Lacroix-Desmazes generally taught a method of treating a subject in need of treatment for a disease [see claims 1-4] (e.g., cancers [0307] generally, including advanced solid tumors [claim 59, ¶s 0050, 0276]). Pharmaceutical compositions comprising pharmaceutically acceptable carriers were taught [0215-0217, 0219, 0221, 0257, 0292, 0296-0297], including those comprising hFIX-encoding AAV8 vectors [0344] (e.g., reads on pharmaceutical composition comprising a transgene). Vectors were taught as encapsulated or complexed with lipid nanoparticles [0243-0246], wherein nanoparticles were generally formed with cationic lipids [0248-0252]. Vector genomes as plasmids were also taught [0099, 0131, 0206, 0266] (e.g., reads on the elected species of dsDNA).
Lacroix-Desmazes taught AAV8 vector, a viral vector; however, was silent a non-viral vector, as recited in claim 1. Lacroix-Desmazes generally taught cationic lipids; however, was silent the instantly elected lipid. Lacroix-Desmazes generally taught cancers, including advanced solid tumors; however, did not teach administering a phagocyte-depleting agent, as recited in claim 1, and as instantly elected.
Qu taught vectors comprising transgenes [0013] for delivery to a subject in vivo or ex vivo [0209], wherein non-viral vectors are suitable vectors [0197-0198].
Since Lacroix-Desmazes generally taught vectors comprising transgenes, it would have been prima facie obvious to include, within the teachings of Lacroix-Desmazes, non-viral vectors, as taught by Qu. The ordinarily skilled artisan would have been motivated to include a suitable vector for the delivery of transgenes, as taught by Qu [0013, 0197-0198].
The combined teachings of Lacroix-Desmazes and Qu did not teach the elected lipid.
Dimitrov taught lipid nanoparticles comprising, as a cationic lipid,
PNG
media_image2.png
117
367
media_image2.png
Greyscale
[see Dimitrov at claim 5].
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, it is prima facie obvious to select
PNG
media_image2.png
117
367
media_image2.png
Greyscale
for incorporation into a lipid nanoparticle, based on its recognized suitability for its intended use as a cationic lipid, as taught by Dimitrov at claim 5.
Although Lacroix-Desmazes generally taught treating advanced solid tumors, the combined teachings of Lacroix-Desmazes, Qu and Dimitrov did not teach administering a phagocyte-depleting agent, as recited in claim 1, further limited to the instant election of emactuzumab.
Cassier taught that emactuzumab, when administered to patients having an advanced solid tumor, resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile [abstract].
Since Lacroix-Desmazes generally taught treating advanced solid tumors, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the art, emactuzumab, as taught by Cassier. The ordinarily skilled artisan would have been so motivated, because emactuzumab, when administered to patients having an advanced solid tumor, resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile, as taught by Cassier at the abstract.
The combined teachings of Lacroix-Desmazes, Qu, Dimitrov and Cassier read on claims 1, 6, 9-11, 20-21 and 25.
Claim 2 is rendered prima facie obvious because Lacroix-Desmazes taught transgene expression in the subject [0063, 0066, 0069, 0339, 0344, 0346].
Claims 3-4 are rendered prima facie obvious because Lacroix-Desmazes taught the transthyretin promoter [0114, 0211].
Claim 5 is rendered prima facie obvious because Qu taught, as an enhancer, ApoE [0172]. Lacroix-Desmazes taught, as a promoter, hAAT [0114]. The motivation to combine Qu with Lacroix-Desmazes was previously discussed.
Claims 6-7 are rendered prima facie obvious because Lacroix-Desmazes taught active agents administered concurrently or in a series or sequentially (prior to or following each other), as set forth by the skilled artisan [0286, 0299].
Claim 15 is rendered prima facie obvious because Lacroix-Desmazes taught an immunosuppressive agent [0240, 0291, 0294-0297].
Claim 19 is rendered prima facie obvious because Qu taught that clinical experience with the vectors demonstrated no sustained toxicity, and that immune responses were minimal or undetectable [0198]. The motivation to combine Qu with Lacroix-Desmazes was previously discussed.
Claim 23 is rendered prima facie obvious because Lacroix-Desmazes taught the vector encoding a therapeutic protein [0096-0097].
Claim 26 is rendered prima facie obvious because Dimitrov taught a molar ratio of the cationic lipid at 20-60 % [0141]. The motivation to combine Dimitrov with Lacroix-Desmazes was previously discussed.
The instant claim 26 recites about 20 mole % to 65 mole % lipid. Dimitrov taught the elected lipid at 20-60 mole %. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claim(s) 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Lacroix-Desmazes (WO 2020/016318 A1), in view of Qu et al (WO 2018/226887 A1), further in view of Dimitrov et al (US 2021/0346306 A1), further in view of Cassier et al (European Journal of Cancer, 141, 2020, 162-170) and further in view of Miyano et al (US 2019/0046551 A1).
The 35 U.S.C. 103 rejection over Lacroix-Desmazes, Qu, Dimitrov and Cassier was previously discussed.
Additionally, Lacroix-Desmazes generally taught treating cancer, as discussed.
The combined teachings of the prior art did not teach a bisphosphonate, further limited to clodronate, as instantly elected, and as recited in claims 12-14.
Nevertheless, Miyano taught clodronate as an antitumor agent, recognized as an anticancer antibiotic [0073].
Since Lacroix-Desmazes generally taught treating cancer, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the prior art, clodronate, as taught by Miyano. The ordinarily skilled artisan would have been motivated to include an anticancer antibiotic, as taught by Miyano [0073]. It is prima facie obvious to select clodronate for incorporation into a composition, based on its recognized suitability for its intended use as an example of an antitumor agent, recognized as an anticancer antibiotic, as taught by Miyano et al [0073].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELESTE A RONEY whose telephone number is (571)272-5192. The examiner can normally be reached Monday-Friday; 8 AM-6 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CELESTE A RONEY/Primary Examiner, Art Unit 1612
Prosecution Insights