DETAILED ACTION
Receipt of Arguments/Remarks, amendments to the drawings and specification filed on November 17 2025 are acknowledged. Claims 1, 12, 23-24 and 27-28 were amended. Claims 1-28 are pending.
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 .
Withdrawn Objections/Rejections
The amendments to the drawings filed November 17 2025 are sufficient to overcome the objection to the drawings. The drawings now all include the appropriate number followed by letter. Acknowledgement is made of the amendments to the specification correcting reference to the updated figures.
The amendments filed November 17 2025 are sufficient to overcome the objection of claim 1. The duplicate figures have been removed from the claim.
The amendments filed November 17 2025 are sufficient to overcome the rejection of claims 12-14, 23-24 and 27-28 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. The amendment to claim 12 now clearly indicate that the ligand is an additional component and conjugated with the molecule, which has antecedent basis in the preamble of claim 1. The indefinite language has been removed from claim 27. Claim 28 has been amended to recite endosomolytic agent, which is defined in paragraph 00158 of the instant specification.
The amendments filed November 17 2025 are sufficient to overcome the rejection of claim 28 under 35 U.S.C. 102(a)(1) over Manoharan et al. (USPGPUB No. 20110123520). The claim was amended to require a particular structure in the linker.
The amendments filed November 17 2025 are sufficient to overcome the rejection of claims 27-28 under 35 U.S.C. 103 over Qasba et al. (WO2005051429) in view of Manoharan et al. (USPGPUB No. 20110123520). The prior art does not teach the linkers are instantly claimed.
The terminal disclaimer filed on November 17 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11286482 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Therefore, the rejection on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 11286482 is withdrawn.
The amendments filed November 17 2025 are sufficient to overcome the rejection of claim 28 on the ground of nonstatutory double patenting over U.S. Patent No. 8575123, U.S. Patent No. 9345780, U.S. Patent No. 9895448, U.S. Patent No. 9127274, U.S. Patent No. 9376680, 9133461, U.S. Patent No. 10125364, U.S. Patent No. 10400239, U.S. Patent No. 11324820, U.S. Patent No. 11229663, U.S. Patent No. 11015201, U.S. Patent No. 11834661, U.S. Patent No. 11149276, U.S. Patent No. 11597932, U.S. Patent No. 11866701. U.S. Patent No. 11162103, 11207416, 11801306, 12274753, 11492623, 12173289, 11987792, 11613751, 12258565, 12365896, 11326166, 11959081, 11866710, 11965166, 11926832, 12049630, 12221607 or 12331297. The linkers claimed in the US Patents are of a different structural scope than the instantly claimed linkers.
The amendments filed November 17 2025 are sufficient to overcome the rejection of claim 28 on the ground of nonstatutory double patenting over copending Application No. 18768261, 18620251, 18259887, 18423377, 18717329, 18777691, 18691742, 18986819, 18585922, 18301089, 18427082, 18697297, 18605975, 18687251, 17768914, 18548634, 18373397, 18144276, 18542950, 18547102, 18403912, 18531914, 18572486, 18044401, 17900921, 17974598, 18206116, 18677062, 18507183, 18243133, 18215849, 17973239, 17995699, 17999320, 17907664, 18187741, 18015202, 17802004, 18001050, 17721530, 17765080, 17683423, 17743498, 17773508, 17621029, 17935997, 17836020, 17907366, 17800471, 17798156, 17268206, 17611761, 17588396, 17588393, 17639881, 17619633, 19115562, 18556583, 18551668, 18007007, 18575157, 18572553, 18259887, 18631104, 18837453, 17995035, 18001813, 18247314, 18263155, 17907741, 17794637, 17778366, 17052945 or 18577377. The linkers claimed in the copending applications are of a different structural scope than the instantly claimed linkers.
New Rejections Necessitated by the Amendments filed November 17 2025
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 27-28 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 27 recites the limitation "the linker" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is insufficient antecedent basis for this limitation in the claim. The claim refers to “an endosomal cleavable linker” or a “protease cleavable linker”. The recitation “the linker” does not make it clear what linker is being referred to.
Claim 28 recites the limitation “the linker” in line 2. There is insufficient antecedent basis for this limitation in the claim. The claim refers to “an endosomal cleavable linker” or a “protease cleavable linker”. The recitation “the linker” does not make it clear what linker is being referred to.
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 27-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 27-28 introduce new matter as the claims recite the limitation: protease cleavable linker wherein the linker comprises one or more saccharide units independently selected from…There is no support in the specification for this limitation. The limitation of: protease cleavable linker comprising one or more saccharide units was not described in the specification as filed, and person skilled in the art would not recognize in the applicant’s disclosure a description of the invention as presently claimed. The specification (paragraph 0017; example 11) discloses protease cleavable linkers in Fig. 6 but does not describe the instantly claimed limitation, specifically that these linkers comprise a saccharide. There is no guidance in the specification to select protease cleavable linkers comprising carbohydrates and from MPEP 2163.06: “Applicant should therefore specifically point out the support for any amendments made to the disclosure.” Applicant has not directed the Examiner to the support in the specification for the amendments. Therefore, it is the Examiner’s position that the disclosure does not reasonably convey that the inventor had possession of the subject matter of the amendment at the time of filing of the instant application.
Claim Rejections - 35 USC § 102
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.
Claim(s) 27-28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zartler et al. (J. Biomol NMR, 2011).
The instant application claims a conjugate comprising an effector molecule linked to a ligand via an endosomal cleavable linker or a protease cleavable linker, wherein the linker comprises one or more saccharide units independently selected from Q303-306, Q312-Q317 plus additional specific saccharides.
The instant application claims a conjugate comprising an endosomolytic agent linked with a ligand via an endosomal cleavable linker or protease cleavable linker wherein the linker comprises one or more saccharide units independently selected from Q303-306, Q312-Q317 plus additional specific saccharides.
The instant application provide no limiting definition of effector molecule. While nucleic acids are mentioned, the claims do not limit the claims to a nucleic acid effector molecule. Therefore, any compound which provides an “effect” reads on effector molecule. Same with ligand, the instant claims do not provide a limiting definition of ligand. Regarding endosomolytic ligand. The instant specification indicates that this refers to molecules having endosomolytic properties. This includes polycations, synthetic cationic lipids, etc.
Zartler et al. is directed to the use of 1H-31P GHMBC and covariance NMR to unambiguously determine phosphate ester linkages in complex polysaccharides. As shown in Fig. 1 is the structure of c-PS which is a c-polysaccharide.
PNG
media_image1.png
480
826
media_image1.png
Greyscale
As shown above the structure includes a cationic short chain lipid reading on endosomolytic or effector agent, this is connected to a phosphate, saccharide linker, which is then connected to a ligand with a group comprising O-CH2-CH(OH)-CH(OH)-CH(OH)-CH2-O-P(O)-OH. This linker reads on Q304 or
PNG
media_image2.png
210
290
media_image2.png
Greyscale
(first structure on left; page 8 of claim).
Therefore, c-PS reads on the instant claims as the instant claims provide no limiting definition of effector molecule or endosomolytic agent or ligand, the groups identified above read on these groups. Since the claims recite the linker “comprises”, additional functionality is allowed to be present within the scope of the claim.
Allowable Subject Matter
Claims 1-26 are allowed. The prior art does not suggest a molecule comprising at least two effector molecules selected from the particular claimed list and an endosomal cleavable linker comprising one or more saccharide units independently selected from the particular claimed list. The specifically claimed structure distinguishes the instant claims from the prior art.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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, Neil Hammell can be reached at 571-270-5919. 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.
/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636