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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 14, 2025 has been entered.
Response to Arguments
Applicants' arguments, filed November 14, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Note than while claim 19 was cancelled in the claim amendments filed November 14, 2025, the subject matter contained in this claim has been incorporated into independent claim 1. Therefore, the issues previously identified with claim 19 are not all moot and apply to all claims under examination as detailed below due to their inclusion in claim 1.
Specification
The disclosure was objected to because of the following informalities: trade names or marks used in commerce are present in the specification and are not properly formatted.
The use of the terms RAW-BLUE®, QUANTI-BLUE® and HEK-BLUE®, which are trade names or marks used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Amendments to the specification were filed November 14, 2025 and capitalized the various tradenames but they are still not accompanied by the required generic terminology.
It was also noted that while not a tradename, the acronym SEAP is no longer accompanied the complete unabbreviated term anywhere in the specification and the complete term or phrase should be used at least the first time the abbreviation is used in the specification.
Therefore the specification is still objected to.
Drawings
The drawings were received on November 14, 2025. These drawings are not acceptable.
The drawings remain objected to because there is gray shading behind all the figures and color is still present in figures 7 and 8. There is still no granted petition to accept color drawings and therefore all color must be removed. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112 – New Matter
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 1, 4 – 7 and 12 – 16 were 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 1 recites a chemical structure for a single specific toll-like receptor (TLR) prodrug followed by a semicolon and then the phrase “and a pharmaceutically acceptable salt” as required ingredients in the claimed nanocarrier. However, the disclosure as originally filed does not support nanocarriers comprised of the TLR agonist and a completely separate salt that is pharmaceutically acceptable. The disclosure as originally filed discloses pharmaceutically acceptable salts of the TLR prodrug (e.g., ¶ [0469] of the PGPub of the instant application) and that the nanocarrier can be present in pharmaceutically carriers such as saline [a specific pharmaceutically acceptable salt] or other salt-containing carriers (¶ [0426] of the PGPub of the instant application). However that the nanocarrier itself comprises both the compound of claim 1 and any pharmaceutically acceptable salt is not disclosed by the application as originally filed.
The dependent claims fall therewith.
If Applicant is in disagreement with the Examiner regarding support for the amended claim 1, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention and/or explain how implicit or inherent support is present for the new claim limitations.
Applicants traverse this rejection on the grounds that claim 1 has been amended to clarify that the composition being used comprises both a nanocarrier and a pharmaceutically acceptable salt.
These arguments are unpersuasive. The rejection was and is based on the interpretation stated in the remarks and the addition of the semicolon does not change this interpretation. Compositions comprising a compound of the structure of claim 1 and any pharmaceutically acceptable salt, not just pharmaceutically acceptable salts of the recited compound, are not sufficiently disclosed in the application as originally filed to support the full breadth of the claimed composition as the specification.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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, 4 – 7 and 12 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over Klinman et al. (WO 2014/201245; cited on May, 2, 2024 IDS) in view of Mehnert et al. (Adv Drug Del Rev, 2012). This rejection is MAINTAINED for the reasons of record set forth herein.
Klinman et al. discloses methods for treating a tumor by administering a therapeutically effective amount of a TLR-9 agonist such as CpG ODN and a therapeutically effective amount of a TLR-7 and/or TLR-8 agonist such as an imidazoquinoline compound that act synergistically to treat the tumor in the subject. As shown at the top of p 28, the imidazoquinoline compound can be 3M-052, which is the same compound as compound TR5 shown in instant claim 1. Pharmaceutically acceptable salts of the imidazoquinoline compound are also disclosed (p 30, ln 3 – 17). Pharmaceutical compositions formulated for human or veterinary use are provided and will typically be used to treat human subjects (p 34, ln 4 – 6). Examples of the types of solid tumors given include colon carcinoma, colorectal cancer, breast cancer, hepatocellular carcinoma and melanoma (p 14, ln 14 – 27 and claim 30). Generally the formulations are prepared by contacting the imidazoquinoline compound such as 3M-052 and the one or more CpG ODNA or a combination intimately with liquid carriers and examples of non-aqueous vehicles include liposomes (p 36, ln 6 – 14). Formulations can comprise physiological saline or balanced salt solutions (p 12, ln 7 – 9) that comprise pharmaceutically acceptable salts. Additional agents can also be administered such as a chemotherapeutic agent (p 37, ln 17 onward). Various exemplary chemotherapeutic agents are recited including mitoxantrone (MTO) and TAXOL® (paclitaxel) (p 7, ln 22 – p 8, ln 3 and p 37, ln 23 – p 38, ln 17).
Administration to a human subject or administration 3M-052 in a liposomal formulation is not specifically disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the treatment regimen of Klinman et al. with a human subject having various types of cancer and/or to incorporate the therapeutic agent such as 3M-052 into a liposomal form with a pharmaceutically acceptable salt of the compound and/or present as part of the carrier. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Klinman et al. discloses that human and non-human subjects and various types of tumors can be treated using the disclosed treatment regimen including an imidazoquinoline compound such as 3M-052 even if administration to human subject or formulations in liposomal formulations was only generally disclosed by Klinman et al.
The size (Zav) and zeta potential of the liposomes are not disclosed.
Mehnert et al. discloses that factors such as drug release and biodistribution are determined by the size, surface charge (reflected in the zeta potential), surface hydrophobicity and membrane fluidity of liposomes (p 84, col 2, ¶ 3). Particle aggregation is less likely to occur with charged particles due to electric repulsion (p 92, col 1, ¶ 4).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the nanocarrier liposome size, reflected in Zav, and the surface charge, reflected in the zeta potential. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Mehnert et al. discloses that parameters such as the size and surface charge influence at least drug release and biodistribution of nanosized structures. Depending on a particular application, factors such as the release profile and desired biodistribution localization, one of ordinary skill in the art would routinely optimize such parameters and there is no evidence of record as to the criticality of the claimed invention.
Applicants do not present any specific arguments regarding the applied prior art references or the previous rejection for the Examiner to address herein.
Terminal Disclaimer
The terminal disclaimer filed on November 14, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12,311,010 has been reviewed and is accepted. The terminal disclaimer has been recorded. Accordingly, the nonstatutory double patenting rejections based on this patent have been withdrawn.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Applicants request that the provisional nonstatutory double patenting rejections be held in abeyance until the current claims have been allowed, at which time Applicant asserts the rejections should be properly withdrawn.
The current claims are not in condition for allowance as set forth herein and therefore the propriety of withdrawal of the provisional nonstatutory double patenting rejections will not be considered. The rejections are maintained for the reasons set forth below.
Claims 1, 4 – 7 and 12 – 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 6, 8, 10 – 13, 15, 17 and 18 of copending Application No. 18/445,036 in view of Klinman et al. (WO 2014/201245; cited on May, 2, 2024 IDS), and Mehnert et al. (Adv Drug Del Rev, 2012). This rejection is MAINTAINED for the reasons of record set forth herein.
The claims of US’036 recite a Toll-like receptor (TLR) prodrug as shown in claim 1 that can be further co-formulated with various additional known anti-cancer agents (claims 12 and 13). Various lipids can be present (claim 8).
While no claims of treating cancer are present, particularly given the additional anti-cancer agents that can be present, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to administer the compositions of US’036 to a subject to treat cancer.
Liposomal carriers or specific types of cancers are not claimed.
Klinman et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to administer the compositions of US’036 to a subject to treat a cancer such as melanoma, colorectal carcinoma, breast cancer or hepatocellular carcinoma with the agents disclosed therein or in combination with additional therapeutic agents such as 3M-052 and to formulate as a liposome. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the knowledge of such an artisan and the teachings of Klinman et al. render obvious the use of anti-cancer agent containing compositions to treat cancers such as those claimed. There may not be an absolute expectation of success that such a composition would treat all cancers, one of ordinary skill in the art would have a reasonable expectation that the compositions would be effective in the treatment of cancer. Only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness.
Liposomal carriers with a size (Zav) and zeta potential are not claimed.
Mehnert et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the nanocarrier liposome size, reflected in Zav, and the surface charge, reflected in the zeta potential of the nanocarriers of US’036. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Mehnert et al. discloses that parameters such as the size and surface charge influence at least drug release and biodistribution of nanosized structures. Depending on a particular application, factors such as the release profile and desired biodistribution, one of ordinary skill in the art would routinely optimize such parameters. There is no evidence of record as to the criticality of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4 – 7 and 12 – 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 19 of copending Application No. 19/052,641 Klinman et al. (WO 2014/201245; cited on May, 2, 2024 IDS), and Mehnert et al. (Adv Drug Del Rev, 2012). This rejection is MAINTAINED for the reasons of record set forth herein.
The claims of US’641 recite a method of treating a subject diagnosed with cancer using the Toll-like receptor (TLR) prodrug as shown in claim 1 as a lipid nanoparticle that can be further co-formulated with various additional known anti-cancer agents (claims 5 - 10). The method can be for a human subject (claim 11) diagnosed with melanoma (claim 12) or colorectal cancer (claim 13).
Liposomal carriers or the treatment of breast cancer or hepatocellular carcinoma are not claimed.
Klinman et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to also use the agents of US’641 to treat breast cancer or hepatocellular carcinoma with the agents claimed therein or in combination with additional therapeutic agents such as 3M-052 and to formulate as a liposome as taught by Klinman et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the knowledge of such an artisan and the teachings of Klinman et al. render obvious the use of anti-cancer agent containing compositions to treat cancers such as those claimed. There may not be an absolute expectation of success that such a composition would treat all cancers, one of ordinary skill in the art would have a reasonable expectation that the compositions would be effective in the treatment of cancer. Only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness.
Liposomal carriers with a size (Zav) and zeta potential are not claimed.
Mehnert et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the nanocarrier liposome size, reflected in Zav, and the surface charge, reflected in the zeta potential of the nanocarriers of US’641. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Mehnert et al. discloses that parameters such as the size and surface charge influence at least drug release and biodistribution of nanosized structures. Depending on a particular application, factors such as the release profile and desired biodistribution, one of ordinary skill in the art would routinely optimize such parameters. There is no evidence of record as to the criticality of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 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, Michael Hartley can be reached at 571-272-0616. 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.
/Nissa M Westerberg/Primary Examiner, Art Unit 1618