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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to photoactivatable nanoparticles and a pharmaceutical composition comprising the photoactivatable nanoparticles in the reply filed on 9/15/2026 is acknowledged.
Applicant’s further election of the species of i) liposomes as the species of the form of nanoparticles, ii) BPD-PD and the species of photosensitizer, iii) an α-PD-L1 antibody as the species of immune checkpoint targeting feature, and iv) targeted drugs as the species of the one or more additional treatment agents without traverse in the reply filed on 9/15/2026 is acknowledged.
Claims 9-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/15/2026.
Claims 1-8 are under current examination. The claims were read in view of the species elections detailed above.
Priority
This application claims priority to US PRO 63/612,499, filed 12/20/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/17/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 3 and 6 are objected to because of the following informalities: the abbreviation BPD-PC should be defined in the claims.
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.
Claims 1-8 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites “the immune checkpoint targeting feature”, in line 6. This is indefinite as claim 1 previously recites “at least one immune checkpoint targeting feature”; it is unclear if “the immune checkpoint targeting feature” refers to one or more than one of the “at least one immune checkpoint targeting feature”.
Similarly, claim 1 recites “the photosensitizer”, in line 9. This is indefinite as claim 1 previously recites “at least one photosensitizer”; it is unclear if “the photosensitizer” refers to one or more than one of the “at least one photosensitizer”.
It is suggested that Applicant can rewrite claim 1 to recite “the at least one immune checkpoint targeting feature” in line 6 and “the at least one photosensitizer” in line 9.
Claims 2-8 are rejected under 35 U.S.C. 112(b) by virtue of their dependency on instant claim 1 and failure to cure the deficiencies noted above.
Claims 3 and 6 recite “the photosensitizer is BPD-PC”, respectively. This is indefinite as claim 1, from which claims 3 and 6 depend, previously recites “at least one photosensitizer”; it is unclear if “the photosensitizer” refers to one or more than one of the “at least one photosensitizer”. It is suggested that Applicants can rewrite claims 3 and 6 to recite “the at least one photosensitizer”.
Claims 4 and 6 recite “the immune checkpoint targeting feature is an α-PD-L1 antibody”, respectively. This is indefinite as claim 1, from which claims 4 and 6 depend, previously recites “at least one immune checkpoint targeting feature”; it is unclear if “the immune checkpoint targeting feature” refers to one or more than one of the “at least one immune checkpoint targeting feature”. It is suggested that Applicants can rewrite claims 4 and 6 to recite “the at least one immune checkpoint targeting feature”.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 recites the limitation “up to 35 immune checkpoint targeting features are attached to the nanoparticle”. Per MPEP 2173.05(c) II., “the term "up to" includes zero as a lower limit, In re Mochel, 470 F.2d 638, 176 USPQ 194 (CCPA 1974)”. Claim 1, from which claim 5 depends, requires at least one immune checkpoint targeting feature attached to the nanoparticles. Thus, claim 5, including zero as a lower limit, has broadened the number of attached immune checkpoint targeting features, and fails to include all of the limitations of claim 1.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claims 1-4 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Obaid et al. (US 2022/0142922 A1, published May 12, 2022; included on IDS submitted 01/17/2025), hereafter “Obaid”, in view of Yantasee et al. (US 2022/0249389 A1, published August 11, 2022), hereafter “Yantasee”.
Regarding instant claims 1-3, Obaid teaches a liposome comprising a conjugate comprising a lysophospholipid and a photosensitizer (see entire document, particularly Abstract and claim 1). Obaid teaches that the photosensitizer is a benzoporphyrin derivative (BPD) (paragraph [0058]), and that a BPD LysoPC conjugate formed with 16:0 and/or 20:0 LysoPC can be stably embedded into the into the phospholipid bilayer (attached to the liposome) (paragraph [0063] and Fig. 26); this is consistent with the preparation of BPD-PC described in the instant specification at paragraph [0096]). The liposomes of Obaid further comprise a targeting moiety (claim 1) which can be an antibody (claim 25), and the antibody can be conjugated to the surface of the liposome (paragraphs [0055] and [0070]-[0071] and Fig. 17). The liposomes can be used in the treatment of various cancers (abstract, claim 65, and paragraphs [0005] and [0100]-[0115]). Obaid teaches that the liposomes can be used for light-triggered release of liposomal payloads (paragraph [0118]), that the liposomes can deliver payloads to target cancer cells (paragraph [0176]), and that the selective intracellular delivery of the targeted liposomal platform enables intracellular induction of photodynamic therapy and intracellular phototriggered delivery of biological/chemotherapeutic agents (paragraph [0177]).
Regarding instant claim 7, Obaid teaches a pharmaceutical composition comprising the liposome and a pharmaceutically acceptable excipient (claim 65) which can include a carrier, adjuvants, and auxiliary substances such as pH buffering agents (paragraphs [0094]-[0097]).
Obaid does not teach an immune checkpoint targeting feature of an α-PD-L1 antibody attached to the liposome (instant claims 1 and 4) and does not teach that the pharmaceutical composition comprises the elected species of targeted drugs (instant claim 8).
Yantasee teaches immunotherapeutic constructs comprising a delivery particle, at least one adjuvant, and one or more therapeutic agents/compounds that cause antigen release and/or modulate immunosuppressive tumor microenvironment; the immunotherapeutic constructs create adaptive immunity or anti-cancer immune responses that can be used to prevent and treat broad types of cancer (see entire document, particularly Abstract and claim 1). The delivery vehicle is taught to be a liposome (claim 3), and the at least one therapeutic agent includes one or more anti-cancer agents such as an immune checkpoint inhibitor (claim 20) of an antibody against PD-L1 (claims 21-22). The therapeutic agents may be attached to the surface of the delivery system (paragraphs [0015], [0073], [0126]-[0128]). Yantasee further teaches that the immunotherapeutic construct can be administered in a composition to enhance the effect of an anti-cancer therapy in combination with an anti-cancer agent (claims 33 and 52) such as a targeted therapeutic agent (claim 53). Targeted therapeutics (e.g., small molecule inhibitors or antibodies targeting other oncoproteins, or medical radioactive isotopes) can be loaded directly on/in the immunotherapeutic constructs as a therapeutically active agent (paragraph [0013]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the liposome and composition of Obaid with the immune checkpoint inhibitor anti PD-L1 antibody and the targeted therapeutics of Yantasee. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to achieve a targeted cancer therapy which unleashes the body’s own immune system to attack cancer and which can be used for in situ vaccination strategies in which tumors are locally killed (Yantasee paragraphs [0006] and [0023]); co-administration with anti-cancer agents such as targeted therapeutics provides an enhanced anti-cancer therapy effect (paragraph [0088]). There is a reasonable expectation of success as Yantasee teaches attachment of anti PD-L1 antibodies to the surface of liposomes and the inclusion of targeted therapeutics for the treatment of broad types of cancer; Obaid similarly teaches liposomes for selective intracellular delivery of biological/chemotherapeutic agents for the treatment of various cancers and that antibodies can be conjugated to the surface of the liposome.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Obaid in view of Yantasee as applied to claim 1-4 and 7-8 above, and further in view of Xiang et al. (“Relationship between Targeting Efficacy of Liposomes and the Dosage of Targeting Antibody Using Surface Plasmon Resonance” Langmuir 2015, 31, 12177-12186), hereafter “Xiang”.
The teachings of the modified Obaid are set forth above.
Regarding the number of immune checkpoint targeting features attached to the nanoparticle of instant claims 5-6, as detailed above, the combination of Obaid and Yantasee arrives at a liposome with anti-PD-L1 antibodies attached. Obaid further demonstrates that antibodies such as the anti-EGFR Cetuximab can be conjugated to the surface of liposomes, and that the number of antibodies conjugated per liposome can be adjusted based on the number of antibodies reacted and whether conjugation is site-specific or stochastic; the number of conjugated Cetuximab antibodies ranges from 0 to about 110 per liposome (see particularly paragraphs [0054], [0164], and [0166] and Figs. 12 and 17), consistent with the values of instant claims 5-6.
The prior art of Xiang further teaches that liposomes modified by targeting antibodies exhibit an improved targeting effect as the surface density increases until a certain threshold is reached; further increase does not enhance binding affinity and may even decrease it (see entire document, particularly “Abstract” and “Introduction”, paragraph 3). Xiang demonstrates that the number of antibodies per liposome is affected by the amount of antibody added (see Tables 2 and 3) and the size of the liposome (see Figure 3). Xiang further teaches that larger liposomes offer a much higher association constant and binding affinity than smaller ones, but smaller liposomes have other advantages such as the ability to freely pass through certain biological barriers (see paragraph bridging paragraphs 12182-12183).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to routinely optimize the liposome size, number of antibodies added, and conjugation mode, as suggested by Obaid and Xiang, in order to achieve a number of anti-PD-L1 antibodies attached to the liposome consistent with instant claims 5-6. One of ordinary skill in the art would have been motivated to do so to achieve a surface density of antibodies with good targeting efficiency with a liposome size that achieves the desired biological effect, as suggested by Xiang. Per MPEP 2144.05 II. A. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
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.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-11, 15-18 of copending Application No. 19/578,190 in view of Yantasee et al. (US 2022/0249389 A1, published August 11, 2022), hereafter “Yantasee”, and Xiang et al. (“Relationship between Targeting Efficacy of Liposomes and the Dosage of Targeting Antibody Using Surface Plasmon Resonance” Langmuir 2015, 31, 12177-12186), hereafter “Xiang”.
Both the instant claims and those of copending Application No. 19/578,190 are directed to photoactivatable nanoparticles for use as therapeutic agents in immunotherapy treatments which comprise nanoparticles of liposomes and a photosensitizer of benzoporphyrin derivative bound to phosphatidylcholine, and which are delivered to cancer cells. The copending Application No. 19/578,190 further recite administering the nanoparticles for immunotherapy wherein anti-PD-L1 immune checkpoint inhibitor is conjugated to the particles.
The claims of copending Application No. 19/578,190 do not recite the number of antibodies attached to the nanoparticle of instant claims 5-6, and do not recite the composition and additional targeted drugs of instant claims 7-8.
Yantasee teaches immunotherapeutic constructs comprising a delivery particle, at least one adjuvant, and one or more therapeutic agents/compounds that cause antigen release and/or modulate immunosuppressive tumor microenvironment; the immunotherapeutic constructs create adaptive immunity or anti-cancer immune responses that can be used to prevent and treat broad types of cancer (see entire document, particularly Abstract and claim 1). The delivery vehicle is taught to be a liposome (claim 3), and the at least one therapeutic agent includes one or more anti-cancer agents such as an immune checkpoint inhibitor (claim 20) of an antibody against PD-L1 (claims 21-22). The therapeutic agents may be attached to the surface of the delivery system (paragraphs [0015], [0073], [0126]-[0128]). Yantasee further teaches that the immunotherapeutic construct can be administered in a composition comprising at least one pharmaceutically acceptable carrier, excipient, or diluent to enhance the effect of an anti-cancer therapy in combination with an anti-cancer agent (claims 33 and 52) such as a targeted therapeutic agent (claim 53). Targeted therapeutics (e.g., small molecule inhibitors or antibodies targeting other oncoproteins, or medical radioactive isotopes) can be loaded directly on/in the immunotherapeutic constructs as a therapeutically active agent (paragraph [0013]).
Xiang teaches that liposomes modified by targeting antibodies exhibit an improved targeting effect as the surface density increases until a certain threshold is reached; further increase does not enhance binding affinity and may even decrease it (see entire document, particularly “Abstract” and “Introduction”, paragraph 3). Xiang demonstrates that the number of antibodies per liposome, in amounts consistent with the instant claims, is affected by the amount of antibody added (see Tables 2 and 3) and the size of the liposome (see Figure 3). Xiang further teaches that larger liposomes offer a much higher association constant and binding affinity than smaller ones, but smaller liposomes have other advantages such as the ability to freely pass through certain biological barriers (see paragraph bridging paragraphs 12182-12183).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the liposome of copending Application No. 19/578,190 incorporate it into a composition comprising the targeted therapeutics, as suggested by Yantasee. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to achieve a targeted cancer therapy which unleashes the body’s own immune system to attack cancer and which can be used for in situ vaccination strategies in which tumors are locally killed (Yantasee paragraphs [0006] and [0023]) and provide an enhanced anti-cancer therapy effect via co-administration with anti-cancer agents such as targeted therapeutics (paragraph [0088]).
It would further have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to routinely optimize the liposome size and number of antibodies added, as suggested by Xiang, in order to achieve a number of anti-PD-L1 antibodies attached to the liposome consistent with instant claims 5-6. One of ordinary skill in the art would have been motivated to do so to achieve a surface density of antibodies with good targeting efficiency with a liposome size that achieves the desired biological effect, as suggested by Xiang. Per MPEP 2144.05 II. A. “"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Given the subject matter of the instant claims is obvious and substantially overlaps the subject matter of copending Application No. 19/578,190, the instant claims are rejected on the ground of nonstatutory double patenting. This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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