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 with traverse of the invention of Group I, drawn to a conjugate comprising an immune checkpoint inhibitor that inhibits ligands on the surface of cancer cells and a sonosensitizer, in the reply filed on 03/06/2026 is acknowledged. Applicant further elects the anti-PD-L1 antibody atezolizumab with traverse. The traversal is on the ground(s) that the manufacturing method and the therapeutic method are derivative inventions that are technically inseparable from the conjugate invention; and the respective groups share the same special technical feature and form a single general inventive concept. Further, Applicant argues that the inventive concept does not reside in the individual structural differences among specific PD-L1 inhibitors but rather in the common technical concept of a conjugate comprising an immune checkpoint inhibitor and a sonosensitizer that retains PD-L1 binding capability while exhibiting ultrasound-responsive therapeutic effects. This is not found persuasive because, as discussed in the Restriction Requirement of 01/07/2026, the inventions of Groups I-III lack unity of invention because even though the inventions of these groups require the technical feature of a conjugate comprising an anti-cancer agent (e.g. an immune checkpoint inhibitor) linked to a sonosensitizer, this technical feature is not a special technical feature as it does not make a contribution over the prior art (e.g. Wang et al -US20190070296A1, of record). Further, the claims are directed to more than one species of the generic invention (i.e. conjugate comprising an immune checkpoint inhibitor and sonosensitizer, wherein a different PD-L1 inhibitor recited by the instant claims will yield a different sonosensitizer conjugate. Each PD-L1 inhibitor recited in instant claim 3 can differ in structure (amino acid sequence) and chemical/physical properties (e.g. binding affinity). As such, while any PD-L1 inhibitor can be conjugated to a sonosensitizer, the resulting conjugate species will differ in structure, chemical/physical properties (e.g. binding affinity), and potentially therapeutic efficacy.
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/06/2026.
Claims 1-9 are examined on the merits in the present Office Action.
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.
(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.
Claims 1-5 and 7-9 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Biel et al (US20180250405A1), hereinafter Biel.
Biel discloses a conjugate comprising a phthalocyanine dye linked to a targeting molecule such as an immune checkpoint inhibitor that specifically binds to PD-L1, wherein the phthalocyanine dye is— in some embodiments— IRDye 700DX (IR700) and the immune checkpoint inhibitor is— in some embodiments—selected from the group consisting of atezolizumab, avelumab, MEDI4736 (durvalumab) or BMS-936559 (Para. 0005, Para. 0009, Para. 0066-0067, and Para. 0484). The phthalocyanine dye and an immune checkpoint inhibitor would be present in the conjugate in at least a 1:1 ratio. Phthalocyanines, like IR700, are azaporphyrins that contain four benzoindole groups connected by nitrogen bridges in a 16-membered ring of alternating carbon and nitrogen atoms (i.e., C32H16N8) which form stable chelates with metal and metalloid cations (Para. 0229). In particular, the phthalocyanine dye includes the formula
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525
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,wherein at least one of R4, R5, R6, R9, R10, and R11 include a water-soluble group such as a sulfate (—SO4 −2) group, a hydroxyl (—OH) group, or an amine (—NH2) group (Para. 0025-0029 and Para. 0246). Thus, phthalocyanines - including IR700- can be considered a type of porphyrin, wherein porphyrins are classified as sonosensitizers per the instant claims. Further disclosed are pharmaceutical compositions containing the phthalocyanine-targeting molecule conjugates (e.g. IR700-antibody conjugates) for treating a tumor (Para. 0005, Para. 0068). The term “sonodynamic” recited in instant claim 8 is the intended use of the composition but does not result in any structural differences between the claimed invention and the prior art. The ‘sonodynamic’ composition of the instant claims comprises a conjugate containing a sonosensitizer linked to an immune checkpoint inhibitor; and per the instant claims, porphyrins are types of sonosensitizers. Hence, the compositions disclosed by the prior art are “sonodynamic”.
Thus, Biel meets the limitations of instant claims 1-5 and 7-9.
Claims 1, 4, 5, and 7-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al (Huang, Zeqian et al. “Enhanced cancer therapy through synergetic photodynamic/immune checkpoint blockade mediated by a liposomal conjugate comprised of porphyrin and IDO inhibitor.” Theranostics vol. 9,19 5542-5557. 29 Jul. 2019, doi:10.7150/thno.35343), hereinafter Huang.
Huang discloses a dual functional drug conjugate comprised of protoporphyrin IX and NLG919, a indoleamine-2,3-dioxygenase (IDO) inhibitor (PpIX-NLG) (Abstract). The protoporphyrin IX and NLG919 would be present in the conjugate in at least a 1:1 ratio. IDO is an immune checkpoint ; therefore, NLG919 is an immune checkpoint inhibitor (Introduction, 3rd paragraph). Porphyrins are further by instant claim 4 as a type of sonosensitizer; and protoporphyrin IX, in particular, comprises carboxyl groups as shown Scheme 1. The conjugate disclosed by Huang therefore comprises a sonosensitizer linked to an immune checkpoint inhibitor, wherein the sonosensitizer comprises carboxyl (-COOH) groups. Further disclosed is liposomal delivery of PpIX-NGL to bilateral 4T1 tumor-bearing mice to inhibit both primary and distant metastatic tumor (Abstract). As such, a composition comprising the conjugate as an active ingredient for the treatment of cancer is also disclosed. The term “sonodynamic” recited in instant claim 8 is the intended use of the composition but does not result in any structural differences between the claimed invention and the prior art. The ‘sonodynamic’ composition of the instant claims comprises a conjugate containing a sonosensitizer linked to an immune checkpoint inhibitor; and per the instant claims, porphyrins are types of sonosensitizers. Hence, the compositions disclosed by the prior art are “sonodynamic”.
Thus, Huang meets the limitations of instant claims 1, 4, 5, and 7-9.
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.
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 1-5 and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Han (US 20020155999 A1) in view of Akinleye (Akinleye, Akintunde, and Zoaib Rasool. “Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.” Journal of hematology & oncology vol. 12,1 92. 5 Sep. 2019, doi:10.1186/s13045-019-0779-5), hereinafter Akinleye.
Han teaches an anti-cancer substance comprising a porphyrin-like molecule conjugated to an anti-cancer drug, wherein the porphyrin-like molecule is a porphyrin, protoporphyrin-IX, or heme (Abstract and Para. 0025). The porhyrin-like molecule and anti-cancer drug would be present in the conjugate in at least a 1:1 ratio. Heme consists of a planar tetrapyrrole ring system with a chelated iron ion at the center and has two carboxyl groups as well as hydrophobic methyl and vinyl groups (Para. 0007). Thus, heme is a sonosensitizer comprising one or more carboxyl groups per instant claims 4 and 5. Further disclosed is a method of treating a tumor in a patient comprising administering the porphyrin-like-drug conjugate in a pharmaceutically acceptable carrier (Para. 0042); and thus is provided as an active agent in a composition for the treatment of cancer. The ‘sonodynamic’ composition of the instant claims comprises a conjugate containing a sonosensitizer linked to an immune checkpoint inhibitor; and per the instant claims, porphyrins are types of sonosensitizers. Hence, the compositions disclosed by the prior art are “sonodynamic”.
Han does not specifically teach that the anti-cancer drug is an immune checkpoint inhibitor, in particular a PD-L1 inhibitor such as atezolizumab.
However, Akinleye teaches that PD-1/PD-L1 signaling negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to evade an antigen-specific T cell immunologic response, thus promoting cancer development and progression. Blockade of this pathway with either PD-1 or PD-L1 immune checkpoint inhibitors significantly enhance antitumor immunity, produce durable clinical responses, and prolong survival across many different solid and hematologic malignancies (Abstract and “Immune checkpoint inhibitors of PDL1 as cancer therapeutics” section). The PD-L1 inhibitors specifically disclosed include atezolizumab, durvalumab, avelumab, envafolimab, BMS-936559, CS-1001, SHR-1316(HTI-1088), and BGB-A333 (see Tables 1 and 2).
It would have been obvious to one of ordinary skill in the art to modify the porphyrin-like/anticancer drug conjugate (e.g. heme-anticancer drug conjugate) disclosed by Han such that the anti-cancer drug is a PD-L1 inhibitor such as atezolizumab. One of ordinary skill in the art would have been motivated to do so since blockade of the PD-1/PD-L1 signaling pathway with a PD-L1 inhibitor such as atezolizumab enhances antitumor immunity, produces durable clinical responses, and prolongs survival across many different solid and hematologic malignancies as taught by Akinleye. Therefore, one of ordinary skill in the art would have reasonably expected that that a porphyrin-like molecule conjugated to a PD-L1 inhibitor such as atezolizumab in a 1:1 ratio can effectively treat cancer in a subject.
Conclusion
Claims 1-5 and 7-9 are not allowable. Claim 6 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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