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 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/25/2026 has been entered.
Claims 1, 6, and 43 are amended and claims 7, 9, 13, 15-18, 20, 22, 25-28, 30, 32-33, 36-37, 40-42, 44-48, 52-54, and 56-57 are cancelled. Claims 1-6, 8, 10-12, 14, 19, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are currently pending and are examined on the merits herein.
Priority
The instant application, filed 06/02/2022, is a 371 filing of PCT/US2020/063444, filed 12/04/2020, which claims domestic benefit to US provisional application 62/945,053, filed 12/06/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/25/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action of 10/28/2025,
The claims were objected to for not having proper amendment markups. Applicant’s amendment to clearly identify amendments to the claims has overcome the objection and the objection is withdrawn.
Claim 41 was rejected under 35 USC 103 and on the grounds of double patenting. The cancellation of the claim has rendered the rejections moot and the rejections are withdrawn.
The following rejections have been modified to add further support from the cited prior art.
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 1-6, 8, 10-12, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are rejected under 35 U.S.C. 103 as being unpatentable over Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817 in view of US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018.
Nagaya teaches that near infrared-photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC) and that programmed death protein-1 ligand (PD-L1) is emerging as a molecular target. Nagaya describes the efficacy of NIR-PIT using fully human IgG1 anti-PD-L1 monoclonal antibody, avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441, papillary adenocarcinoma of lung, cell line (abstract).
Nagaya teaches that several monoclonal antibodies directed against PD-L1 and PD-1 have demonstrated clinical benefit in patients with melanoma, Hodgkin’s lymphoma, lung, and bladder carcinomas, and several other tumor types. The mode of action of these antibodies is to inhibit the interaction between PD-1 on immune cells and PD-L1 on tumor cells, thus reducing or eliminating immunosuppressive signals and leading to enhanced immune cell activation. Avelumab (MSB0010718C) is a fully human IgG1 anti-PD-L1 antibody with potential ADCC properties that, at the time publication, was currently in clinical trial. Despite promising early results, the treatment had not been successful in all patients (page 8807, paragraph bridging columns).
NIR-PIT is a newly developed cancer treatment that employs a targeted monoclonal antibody-photo-absorber conjugate (APC). The photo-absorber, IRDye700DX, or IR700, silica-phthalocyanine dye, is a highly hydrophilic dye, differentiating it from prior hydrophobic dyes used in photodynamic therapy. At the time of publication, the first-in-human phase 1 trial of NIR-RIT with the APC targeting epidermal growth factor receptor (EGFR) in patients with inoperable head and neck cancer was underway (page 8808, left column, paragraph 1).
Nagaya teaches that NIR-PIT had been shown to be effective with a variety of different antibodies and teaches an investigation of avelumab-IR700 as a candidate APC for NIR-PIT. Using a PD-L1 expressing papillary adenocarcinoma of lung cell line, H441, in vitro tumor binding, in vivo tumor accumulation and intratumoral distribution were evaluated. Avelumab-IR700 was then studied in vitro and in a tumor-bearing mouse model in vivo (page 8808, paragraph bridging columns).
In the studies performed by Nagaya, 100 μg of avelumab-IR700 was administered via i.v. and NIR light was administered at 50 J/cm2 on day 1 after injection and 100 J/cm2 on day 2 after injection with a 700 nm fluorescence channel (page 8814, paragraph bridging columns).
Nagaya teaches that treatment with the conjugate and light exposures resulted in rapid cell death in vitro and tumor growth reduction and survival improvement in vivo (page 8812, left column, paragraph 1).
Nagaya concludes that NIR-PIT using avelumab-IR700 can induce significant therapeutic responses after only a single injection of the conjugate and two light exposures in a PD-L1 expressing animal tumor model. Thus, NIR-PIT utilizing PD-L1 as the targeting antigen for the APC might be successful in treating cancers that have not previously responded to the naked antibody alone (paragraph bridging pages 8812-8813).
Nagaya differs from the instantly claimed invention in that, in the study performed by Nagaya, two, not one, light exposures were used.
US’405 teaches a phthalocyanine dye, for example IR700, linked to an immune modulating agent that binds to an immunosuppressive molecule expressed on tumor cells, for example an immune checkpoint molecule, including PD-L1. US’405 further teaches that the immune checkpoint inhibitor is an antibody or antigen binding antibody fragment that binds PD-L1. Exemplary anti-PD-L1 antibodies include, but are not limited to, BMS-935559, MEDI4736, MPDL3280A, and MSB0010718C (which is avelumab as evidenced by Nagaya). US’405 teaches that the conjugates can be used in methods of photoimmunotherapy, for example, by irradiation with light at a wavelength sufficient to activate the dye (page 45, [0493]). US’405 further exemplifies an anti-PD-L1-IRDye 700DX conjugate (page 77, [1066]).
US’405 teaches that the cells, or subjects, can be irradiated one or more times (page 40, [0444]) and that a single irradiation can be performed to effect activation in order to cause PIT-induced cell killing of tumor cells expressing the immunosuppressive molecule, e.g., PD-L1 (page 46, [0499]). US’405 teaches that activation of the dye-conjugate by irradiation with absorbing light, such as NIR light, excites the photosensitizer and results in cell killing, thereby reducing or eliminating the lesion and treating the disease or condition. In some cases, the use of light in the NIR range leads to deeper tissue penetration resulting in successful eradication of tumors after only a single dose of external NIR light irradiation (page 13, [0206]).
US’405 teaches that a therapeutically effective amount or concentration of the conjugate is one that is sufficient to prevent advancement, such as metastasis, delay progression, or to cause regression of a disease, or which is capable of reducing symptoms caused by a disease, such as cancer. In some embodiments, the methods are sufficient to increase the survival time of the patient with a tumor (page 32, [0388]). US’405 further teaches that in a population of subjects treated with the conjugate, the provided methods result in a complete response (CR) in at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% of the treated subjects (page 50, [0527]). US’405 further teaches that a desired response is increased survival time of a patient with a tumor evident by an increase in one or more survival indicators from among duration of median progression-free survival, duration of response, or median overall survival (page 49, [0522]).
US’405 teaches that the disclosed methods can be used as an initial treatment for cancer either alone, or in combination with radiation or other chemotherapies. The methods can also be used in patients who have failed previous radiation or chemotherapy or who have received other therapies that did not provide a desired therapeutic response or outcome. The disclosed methods can also be used in patients with localized and/or metastatic cancer (page 32, [0382]). As US’405 teaches treatment as an “initial treatment” an ordinarily skilled artisan would reasonably envision that the subject can be naïve to treatment, including with an immune checkpoint inhibitor.
US’405 teaches that the cancer may include metastasis and invasion of surrounding or distant tissues or organs, such as lymph nodes, etc. Metastatic disease may refer to cancer cells that have left the original tumor site and migrated to other parts of the body, for example via the bloodstream or lymph system (page 30, [0367]).
US’405 further teaches anti-cancer agents that can be administered in combination with photoimmunotherapy employing phthalocyanine dye-targeting molecule conjugates including any agent that can reduce, arrest, or prevent cancer in a subject. Optionally, an additional anti-cancer immune modulating agent can be used in combination therapy with the conjugate (page 47, [0500]-[0501]). US’405 teaches that the combination therapy can increase the killing of the tumor cells compared to cell killing in therapy methods using only the conjugate or methods involving a monotherapy with the immune modulating agent or anti-cancer agent alone (page 49, [0521]).
US’405 teaches that the cells are irradiated with a therapeutic dose of radiation at a wave length from within a range of 400 to 900 nm, or 690±50 nm (page 39, [0437]) applied about 30 minutes to about 48 hours after administering the conjugate (page 40, [0443]). US’405 further teaches dosages of 1 to about 1000 J/cm2 including 25, 50, 75, 100, 150, 200, 300, and 400 J/cm2 and 1 J/cm fiber length to 500 J/cm fiber length (page 39, [0438]-[0439]). In some embodiments, the first irradiation with light is provided to the tumor after administration of the first conjugate, for example, from about 12 – 48 hours, such as about or approximately 24 hours after administration of the conjugate. The tumor is treated with light to kill cancer cells that express the immunosuppressive molecule, such as to kill tumor cells that express PD-L1. In some embodiments, the killing of such cancer cells may permit re-activation of or amplification of T cell responses at the tumor (page 46, [0498]).
US’405 further teaches methods of treating a disease or condition including administering a therapeutically effective amount of the conjugate, wherein the conjugate binds to a cell present in the microenvironment or a lesion associated with a disease or condition, and, after administering the conjugate, irradiating the lesion at one or more wavelengths to induce phototoxic activity of the conjugate, thereby treating the disease or condition (pages 11-12, [0156]).
US’405 teaches that the conjugate can be used to treat a lesion, where the lesion is a tumor, and the tumor is cancer including cancer of the head and neck, breast, liver, colon, ovary, prostate, pancreas, brain, cervix, bone, skin, lung, or blood (page 30, [0367]). US’405 further teaches cancers including lymphoma, multiple myeloma, colorectal cancer, non-small cell lung cancer, renal cell carcinoma, and stomach cancer (page 30, [0368]-[0369]).
US’405 further teaches that PD-L1, also known as CD274 and B7-H1, and PD-L2, are ligands for PD1, found on activated T cells, B cells, myeloid cells, macrophages, and some types of tumor cells. Anti-tumor therapies have focused on anti-PD-L1 antibodies. The complexes of PD1 and PD-L1 inhibits proliferation of CD8+ T cells and reduces the immune response (page 43, [0476]).
US’405 further teaches that the targeting molecule binds to a cell that is a cancer cell, a tumor cell or an immune cell, such as a T cell, a B cell, a natural killer (NK) cell, a dendritic cell, a macrophage, or a neutrophil (page 19, [0266]). US’405 further teaches that, in the case of tumors, the tumor microenvironment has mechanisms to suppress the immune system, thereby evading immune recognition and preventing or reducing killing of tumor cells. For example, in some cases, immune checkpoint proteins can be dysregulated in tumors, thereby resulting in a suppression of the immune response in the tumor microenvironment as a mechanism of evading the immune system. In some cases TIL can include Tregs, which are cells that are capable of suppressing proliferation of other T cells in the microenvironment (pages 19-20, [0271]).
US’405 further teaches that the targeting molecule binds to a cell surface protein on a tumor or cancer cell. In some embodiments, the targeting molecule binds to a cell surface protein on an immune cell or other non-cancerous cell present in a tumor microenvironment. For instance, a cell surface protein on the surface of a T lymphocyte, such as a Treg, a dendritic cell, a NK cell, a B cell, a macrophage or other immune cell that is present in a tumor microenvironment (page 20, [0272]).
US’405 teaches that the phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. Features of the conjugates, compositions, and methods, including the dose of the conjugate, provide various advantages, such as lower toxicity and/or improved efficacy (abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Nagaya to substitute the two illuminations taught by Nagaya with one illumination as taught by US’405. It would have been obvious to use one illumination as US’405 demonstrates that the prior art recognized one illumination as an alternative to two illuminations with the use of phthalocyanine-dye conjugates. Additionally, US’405 teaches that the use of light in the NIR range leads to deeper tissue penetration resulting in successful eradication of tumors after only a single dose of external NIR light irradiation. An ordinarily skilled artisan would have had a reasonable expectation of success as both Nagaya and US’405 teach the use of phthalocyanine-dye conjugates, including PD-L1 conjugated with IR700, for the treatment of cancer and US’405 recognizes alternative numbers of illumination as being effective for such treatment.
Regarding claims 6, 8, and 10-12, as discussed in detail above, US’405 teaches that the anti-PD-L1 IR700 conjugate can be used to treat cancer including metastasis invading of surrounding or distant tissues or organs. US’405 teaches that metastatic disease may refer to cancer cells that have left the original tumor cite and migrated to other parts of the body, suggesting that they are phenotypically and/or genotypically the same as the first tumor. US’405 also teaches a variety of cancers that can be treated with the anti-PD-L1 targeting conjugate including many phenotypically/genotypically distinct types of cancer. As US’405 teaches that these types of metastasis/different cancers can be treated with an anti-PD-L1 IR700 conjugate, an ordinarily skilled artisan would reasonably expect that treating the tumor or lesion using the method taught by the combination of Nagaya and US’405 would result in the further inhibition, delay, or prevention in the appearance, growth, or establishment of one or more second tumors located distally to the first tumor or lesion. An ordinarily skilled artisan would have a reasonable expectation of success as both Nagaya and US’405 teach administration of an anti-PD-L1 IR700 conjugate for the treatment of cancer and demonstrate that such conjugate can treat metastatic cancer as well as various types of cancers.
Furthermore, the limitations recited in the claims are mechanistic outcomes that would flow naturally from the method taught by the combination of Nagaya and US’405 in which PD-L1 expressing tumors are treated with an avelumab-IR700 conjugate followed by NAR light exposure.
MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
For instance, Nagaya and US’405 teaches that such administration results in rapid cell death in vitro and tumor growth reduction and survival improvement in vivo. While Nagaya does not explicitly demonstrate that the administration of the conjugate to treat the tumor would result in the further inhibition or delay of the appearance, growth or establishment of one or more second tumors or lesions distally located to the first treated tumor or lesion, this result would flow naturally from administration of the conjugate in the treatment of the initially targeted lesion. That is to say that administration of the conjugate to treat the initial cancer would naturally result in the outcomes claimed for one or more second tumors whether Nagaya and US’405 recognized such outcomes or not. This is particularly the case as no further steps are required for the treatment of such secondary tumors beyond the first initial administration of the conjugate and illumination.
Regarding claim 21, an ordinarily skilled artisan would have reasonably expected that the treatment method taught by the combination of Nagaya and US’405 would delay regrowth or prolong duration of remission based on the teachings of US’405 which teaches that administration of an anti-PD-L1 IR700 conjugate and subsequent illumination can result in complete responses and increase survival indicators such as duration of median progression-free survival, duration of response, or median overall survival.
Regarding claim 29, as discussed in detail above, Nagaya teaches that monoclonal antibodies against PD-L1 and PD-1 have demonstrated clinical benefit with the mode of action of these antibodies being the inhibition of the interaction between PD-1 on immune cells and PD-L1 on tumor cells, thus reducing or eliminating immunosuppressive signals leading to enhanced immune cell activation. Nagaya also teaches that administration of an avelumab IL700 conjugate might be successful in treating cancers that have not responded to the naked antibody alone.
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method to treat a subject who had been previously treated with an anti-PD-1 antibody. It would have been obvious to treat this patient population as Nagaya suggests treatment of patients who were treated with a naked anti-PD-L1 antibody which, based on the teachings of Nagaya as a whole, has the same mode of action as anti-PD-1 antibodies, which is the inhibition of the anti-PD-1/PD-L1 pathway. As such, it would have been obvious to treat a subject who had previously been treated with either antibody type with a reasonable expectation of success. The treatment of this patient population is further supported by US’405, which teaches the treatment of patients who have received other therapies that did not provide a desired therapeutic response or outcome.
Regarding claims 34-35, as discussed in detail above, US’405 teaches that the conjugate can target a tumor cell, cancer cell, or an immune cell or other non-cancerous cell present in a tumor microenvironment. For instance, activated T cells, B cells, myeloid cells, macrophages, and some types of tumor cells. Additionally, US’405 teaches that PD-L1 is expressed on these immune cells, indicating that the PD-L1 targeting conjugate in the method taught by Nagaya and US’405 would target such cells based on the use of the PD-L1 antibody in the conjugate. Therefore, one of ordinary skill in the art would reasonably expect that the method would result in the killing of PD-L1 expressing immune cells including myeloid cells and macrophages.
Furthermore, the limitations of claims 34-35 would flow naturally from the administration of the avelumab-IR700 and, therefore, cannot be the basis for patentability when the differences would have otherwise been obvious. See MPEP 2145 II. That is to say that the administration of the anti-PD-L1 IR700 conjugate in the methods of Nagaya and US’405 would naturally find and bind cells that express PD-L1 and, upon NIR light exposure, result in killing of the cells whether Nagaya and US’405 recognized immune cells in addition to the tumor cells or not, and cannot be the basis for patentability when the differences would have otherwise been obvious. See MPEP 2145 II.
Regarding claims 38-39, US’405 further teaches that the complex of PD1 and PD-L1 inhibits proliferation of CD8+ T cells and reduces the immune response (page 43, [0476]). US’405 further teaches that phthalocyanine-dye conjugates containing an immune modulating agent that binds to PD-L1 can be administered to both enhance an immune response and to specific kill cancer cells that express the immunosuppressive molecule, thereby reversing immune suppression in the tumor microenvironment (page 45, [0492]). Based on these teachings, one of ordinary skill in the art would reasonably expect that the method taught by the combination of Nagaya and US’405 would result in an enhanced immune response including increases in the proliferation of CD8+ T cells in the tumor microenvironment.
Furthermore, the claimed increases in the number, level or activity of immune cells in the microenvironment, increases in the number or level of CD8+ T cell infiltration in the tumor or lesion, and/or in the number or level of memory T cells in the vicinity of the tumor or lesion are outcomes that would flow naturally from administration of the conjugate. That is to say that administration of the avelumab-IR700 conjugate would naturally reduce or eliminate immunosuppressive signals leading to enhanced immune activation, as taught by Nagaya and US’405 (page 8807, right column, paragraph 1), which would naturally result in the claimed outcomes whether Nagaya and US’405 recognized them specifically or not, and cannot be the basis for patentability when the differences would have otherwise been obvious. See MPEP 2145 II.
Claims 4, 14, 19, 34-35, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817 in view of US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018 as applied to claims 1 and 2 and in further view of Tang, F. and P. Zheng (2018) Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci 8(34); 1-8.
It is noted that claims 4, 34-35, and 38-39 were rejected above over the combination of Nagaya and US’405. The claims are further rejected here to further demonstrate that a person of ordinary skill in the art would have reasonably expected the killing of immune cells in the target area, and an increase in the number, level, or activity of immune cells, such as CD8+ T cells, in the tumor or lesions.
The combination of Nagaya and US’405 teaches the methods of claim 1 and 2 as discussed in detail above.
As discussed in detail above, US’405 teaches that the anti-PD-L1-IR700 conjugate targets an immune cell or other non-cancerous cell present in a tumor microenvironment, for instance a T lymphocyte, such as a Treg, a dendritic cell, a NK cell, a B cell, a macrophage, or other immune cell that is present in the tumor microenvironment (page 20, [0272]). US’405 also teaches that such cells express PD-L1 and; therefore, would naturally be targeted by the anti-PD-L1 antibody conjugate taught by Nagaya and US’405.
The combination of Nagaya and US’405, however, does not disclose that that the tumor cell does not express or has a reduced expression of an immune checkpoint protein selected from PD-L1, PD-1, and CTLA-4, or that the tumor comprises PD-L1 negative tumor cells.
Tang teaches that antibody blockade of the PD-1/PD-L1 signaling pathway has elicited durable antitumor responses in the therapy of a broad spectrum of cancers. PD-L1 is constitutively expressed in certain tumors and host immune cells and its expression can be induced or maintained by many factors. The expression of PD-L1 on tumor tissues has been reported to be positively correlated with the efficacy of anti-PD-1/PD-L1 therapy in patients. However, multiple clinical trials indicate that patients with PD-L1 negative tumors also respond to this blockade therapy, which suggests the potential contribution of PD-L1 from host immune cells. Recent to the publication, six articles had independently evaluated and verified the contributions of PD-L1 from tumor versus non-tumor cells in various mouse tumor models. The reports highlight the essential roles of PD-L1 from host myeloid cells in negatively regulating T cell activation and limiting T cell trafficking (abstract). Tang provides an overview of the studies which included tumor cells from sarcoma, colorectal tumors, melanoma, lymphoma, lung cancer, and ovarian cancer (page 3, Table 1).
In studies of ovarian cancer, melanoma, and lung cancer tumor models, it is taught that PD-L1 on tumor cells does not contribute to PD-L1 blockade efficacy, rather, PD-L1 on host DCs and macrophages predicts clinical efficacy to PD-L1 blockade (page 3, Table 1, last row, last column). Tang teaches that, in mice bearing PD-L1 deficient tumors, anti-PD-L1 treatment reduced tumor growth. In the study, a correlation is shown between expression of PD-L1 on dendritic cells (DCs)/macrophages and the efficacy of treatments with either anti-PD-1 alone or in combination with anti-CTLA4. It was concluded that the host immune system is indispensable for PD-1/PD-L1 blockade therapy, and the host DCs and macrophages-derived PD-L1, rather than cancer cell-intrinsic PD-L1, predominantly accounts for blocked therapeutic efficacy (page 4, right column, paragraph 2).
Tang teaches that taken together, the independent studies discussed largely complement and validate each other. The work provided extends the mechanisms of action of PD-1/PD-L1 blockade therapy into the tumor microenvironment and largely supports the concept that PD-L1 acts as a molecular shield on both tumor cells and host immune cells to prevent tumors from cytolysis by T cells. PD-L1 expressed on cancerous cells is not exclusively responsible for the therapeutic effect of PD-1/PD-L1 checkpoint blockade, whereas PD-L1 on both malignant and immune cells works concretely to functionally modulate the CTLs in the tumor microenvironment. Therefore, PD-L1 from both sources could be predictive of sensitivity to therapeutic agents targeting the PD-1/PD-L1 axis (page 6, right column, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to apply the method taught by the combination of Nagaya and US’405 to treat tumor cells that do not express PD-L1, or comprises PD-L1 negative tumor cells, based on the teachings of Tang. It would have been obvious to treat tumor cells that are PD-L1 negative as Tang teaches that PD-L1 negative tumors have responded to PD-L1 blockade and that PD-L1 on either tumor cells or host immune cells contribute to tumor escape. The targeting of PD-L1 on immune cells in PD-L1 negative tumors is further supported by US’405, which teaches that the anti-PD-L1 IR700 conjugates can be used to target either tumor cells or immune cells in the tumor microenvironment for the treatment of cancer. As such, a person of ordinary skill in the art would reasonably expect that the avelumab-IR700 conjugate of Nagaya and US’405 would be capable of targeting PD-L1 expressing immune cells in PD-L1 negative tumors thereby treating the tumor. An outcome which is supported by Tang which teaches that even when PD-L1 knockout tumors were used, anti-PD-L1 therapy remained effective. Additionally, Tang teaches studies of lung cancer, which is the same type of cancer taught by Nagaya for treatment with the conjugate. The cancers taught by Tang also overlap with the cancers disclosed by US’405 for treatment with the conjugates.
Regarding claims 4, 34-35, and 38-39, as discussed in detail above, the combination of Nagaya, US’405, and Tang teach administration of an anti-PD-L1 IR700 conjugate for the treatment of cancer and teaches that the conjugate results in specific binding and cell-specific killing after exposure of the cells to NIR in vivo. A person of ordinary skill in the art would have reasonably expected that PD-L1 expressing immune cells in the target area, such as Tregs, macrophages, and dendritic cells, would also be killed based on the teachings of US’405 and Tang, which would result in increases in CD8+ T cell numbers and activity.
As discussed above, both US’405 and Tang teaches that cells such as Tregs, macrophages and dendritic cells in the tumor microenvironment express PD-L1. Based on these teachings, an ordinarily skilled artisan would reasonably expect that administration of the conjugate of Nagaya and subsequent NIR light exposure would act to kill PD-L1 expressing cells which includes Tregs, macrophages, and dendritic cells in the tumor microenvironment. As Tang teaches that PD-L1 directly suppresses activated tumor-infiltrated antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) (page 6, right column, paragraph 1), an ordinarily skilled artisan would reasonably expect that the killing of PD-L1 expressing cells would result in increased numbers and activity of CD8+ T cells in the tumor microenvironment as PD-1/PD-L1 interactions would no longer be suppressing the activated CTLs.
Furthermore, the increase in the number, level, or activity of immune cells and of CD8+ T cell infiltration in the tumor or lesion or the level of memory T cells in the vicinity of the tumor or lesion being increased after treatment are mechanistic results that would flow naturally from following the suggestions of the combination of applied references whether the references explicitly recognized such result or not, and cannot be the basis for patentability when the differences would have otherwise been obvious. See MPEP 2145 II.
Response to Arguments
Applicant’s arguments in the response filed 02/25/2026 have been fully considered, but are not persuasive.
Regarding the rejection of the claims under 35 USC 103, applicant argues that there is no motivation to modify the two-illumination protocol of Nagaya and that the combination of applied references fails to establish obviousness.
Specifically, applicant argues that Nagaya uses two illuminations and cites various portions of Nagaya in which it is stated that two light exposures were used. Applicant cites Nagaya, p. 8812 as stating “[w]e chose a therapeutic regimen with a single injection of the conjugate and two, not one, light exposures.” Applicant argues that this language is not ambiguous and was a deliberate experimental choice and applicant argues that the teachings convey that one illumination was considered and rejected.
This argument is not persuasive.
It is first noted that explicit motivation in the prior art is not required in order to establish a prima facie case of obviousness.
Explicit motivation in the prior art is not required in order establish a prima facie case of obviousness. MPEP 2143 provides 7 exemplary rationales that may be used to support a conclusion of obviousness, KSR (A)-(G), only one of which requires that there be some teaching, suggestion, or motivation in the prior art. In this case, with regards to the single illumination, the rejection relies on KSR(B) simple substitution of one known element for another; a rationale that only requires that the prior art comprised a method that differed from the claimed method by substitution of some step/element; a finding that the substituted component and their functions were known in the art; and a finding that one of ordinary skill in the art could have substituted the one known element for another, and the substitution would have been predictable.
Additionally, the rejections of the instant office action are based on the combination of applied references and what the combination would have suggested to one of ordinary skill in the art prior to the effective filing date of the claimed invention. See MPEP 2145 (IV). Therefore, Nagaya is not required to teach one light illumination as the limitation is demonstrated to be obvious in view of the teachings of US’405. Specifically, as discussed in detail in the rejection, US’405 teaches phthalocyanine dyes linked to immune modulating agents, including IR700 as well as anti-PD-L1 antibodies, including avelumab, teachings which encompass the same conjugate used by Nagaya in the studies presented. US’405 expressly teaches that irradiation can be performed one or more times and that single irradiation can be performed to effect activation in order to cause PIT-indued cell killing of tumor cells expressing the immunosuppressive molecule. US’405 also expressly teaches that the use of light in the NIR range leads to deeper tissue penetration resulting in successful eradication of tumors after only a single dose of external NIR light irradiation. The teachings of US’405 demonstrate that one illumination was a considered and known alternative to two illuminations and; therefore, would have been an obvious substitution into the method of Nagaya with a reasonable expectation of success.
While Nagaya did use two illuminations, at no point does Nagaya criticize discredit, or otherwise discourage the use of a single illumination, nor does Nagaya suggest that one illumination would not be effective. MPEP 2123 (II) states “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments… Furthermore, ‘[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).”
With regards to US’405, which applicant refers to in the response as “Biel”, applicant argues that one of ordinary skill in the art would not turn to the reference in view of Nagaya’s teachings, which applicant interprets as indicating that two illuminations are “required”. Applicant also argues that US’405 lists many possible illumination regiments, without teaching that a single illumination would be effective in checkpoint resistant tumors. Applicant argues that the rejection uses impermissible hindsight bias using applicant’s disclosure as a roadmap.
While Nagaya used two illuminations in the disclosed study, Nagaya does not teach away from the use of one illumination and; therefore, does not suggest that the two illuminations are required or that one illumination would not work. The prior art, specifically US’405, demonstrates that a single illumination was considered to be an alternative to the two illuminations taught by Nagaya.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, in this case, as discussed in detail above and in the instant office action, US’405 teaches anti-PD-L1-IR700 conjugates for the treatment of cancer, demonstrating that Nagaya and US’405 are analogous art. As such, one of ordinary skill in the art would have been able to substitute the two illuminations in Nagaya with a single illumination, as taught by US’405, with a reasonable expectation of success.
With regards to applicant’s arguments that US’405 does not disclose that a single illumination would be effective in checkpoint resistant tumors, US’405 is not required to teach this limitation as US’405 is not the only applied reference. As discussed above, the rejection is based on the combination of applied references and what the combination would have suggested to one of ordinary skill in the art.
In this case, Nagaya teaches that NIR-PIT using PD-L1 as the targeting antigen of the APC might be successful in treating cancers that have not previously responded to the naked antibody alone, demonstrating that the use of anti-PD-L1-PIT had been considered for the treatment of checkpoint resistant tumors. Even though Nagaya performed experiments with two light exposures, based on the teachings of US’405 that a single light exposure is an alternative to two light exposures and can be effective in killing target cells, one of ordinary skill in the art would have reasonably expected that a single light exposure could be used to treat the patient population of Nagaya. It is noted also that the independent claims do not require any specific degree of treatment, only that after the illumination, the growth, size, or viability of the tumor or lesion be reduced or inhibited to any degree.
Applicant further argues that US’405 teaches the killing of tumor cells, and does not teach or suggest alternatively or additionally targeting PD-L1 expressed on non-tumor cells to kill tumor cells that have reduced expression of or effectively do not express PD-L1.
In the response, applicant equates checkpoint inhibitor resistant tumors to reduced expression or no expression of PD-L1. The reduced expression or lack of PD-L1 expression on tumor cells; however, is not required in the independent claims. Rather, the independent claims only require that the subject have a tumor or lesion comprising a tumor cell that is reduced in susceptibility to treatment with a checkpoint inhibitor. Limitations regarding the expression of PD-L1 are recited in dependent claims. Therefore, neither Nagaya nor US’405 are required to teach such limitations. In the instant office action, the reference Tang is applied to demonstrate that, in cancers with PD-L1 negative tumors, PD-L1 was still known to be expressed on immune cells and, in previous studies, anti-PD-L1 treatment reduced tumor growth in mice bearing PD-L1 deficient tumors. In the rejections of the instant office action, the expression of PD-L1 on immune cells and the targeting of such immune cells in the tumor microenvironment with the anti-PD-L1- phthalocyanine dye conjugate is further supported by US’405, which teaches targeting tumor cells or immune cells in the tumor microenvironment.
Applicant argues that Tang does not provide motivation to kill PD-L1 expressing immune cells. Applicant argues that Tang teaches the use of immune checkpoint blockade and that the antibodies disclosed would only block PD-1/PD-L1 signaling which preserves immune cell function. Applicant argues that, in contrast, the claimed method kills PD-L1 expressing cells via photoimmunotherapy.
In the rejections of the instant office action, additional teachings from US’405 have been added to the rejection to demonstrate that the killing of PD-L1 expressing immune cells in the tumor microenvironment with phthalocyanine dye conjugates was also taught by US’405 in order to further demonstrate that the killing of such cells, not just the blocking of the PD-1/PD-L1 pathway, had been considered. Tang is applied to demonstrate that PD-L1 expressing immune cells were present in PD-L1 negative tumors and could be targeted to treat the cancer.
While applicant further argues that Tang teaches away from the claimed invention, and that killing PD-L1 expressing cells would kill, not increase CD8+ T cell activity, at no point does Tang criticize, discredit, or otherwise discourage the killing of the PD-L1 expressing immune cells and; therefore, Tang does not teach away from the use of the phthalocyanine dye conjugates in PD-L1 negative tumors. As discussed above, MPEP 2123 (II) states “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). ‘A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.’ In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)… Furthermore, ‘[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).”
Furthermore, as discussed in detail in the rejections of the instant office action, US’405 teaches the targeting of immune cells in the tumor microenvironment with phthalocyanine dye conjugates as a means to treat cancer. Teachings which further support the conclusion of obviousness established by the combination of Nagaya, US’405, and Tang.
Additionally, as discussed in the rejection of the instant office action, US’405 and Tang establish that the immune cells in the tumor microenvironment express PD-L1 and; therefore, the anti-PD-L1 phthalocyanine dye conjugates would naturally target these cells based on the expression of PD-L1. The increase in CD8+ t cell activity is a mechanistic result which would flow naturally from following the method taught by the combination of applied references and cannot be the basis for patentability when the differences would have otherwise been obvious. Additionally, MPEP 2145 II. states that “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Applicant further argues that the instant disclosure demonstrates unexpected results. Applicant argues that the instant application demonstrates that phthalocyanine dye conjugates targeting PD-L1 are effective in tumors or lesions with reduced susceptibility to immune checkpoint inhibitors as evidenced by Examples 8-12, 14, and 15. Applicant further argues that Examples 14 and 15, Figs. 13A-C, and 14A-14B show that anti-PD-L1 PIT with a single illumination can effectively treat tumors that are resistant or show reduced susceptibility to checkpoint inhibitor therapy. Applicant argues that Example 14 demonstrates that anti-PD-L1 PIT administration improves survival benefit and decreases tumor volume compared to anti-PDL1-IR700 without illumination or naked anti-PD-L1 antibody, where the anti-PDL1 antibody bound to cells but did not kill the cells; indicating that the benefits were due to the killing by the anti-PDL1-IR700 PIT, not only binding.
Applicant argues that these results show that the claimed benefit is not a predictable extension of checkpoint blockade principles, but from the mechanism of selectively illuminating PD-L1 expressing cells with PIT.
Applicant argues that Example 8 demonstrates that anti-PD-L1-IR700 PIT exhibits anti-cancer activity even in tumors lacking PD-L1 expression and example 9 shows that PIT can target and eliminate PD-L1 expressing non-tumor immune cells in the tumor microenvironment. Applicant argues that additional studies demonstrate increased recruitment of neutrophils, DC, and CD8+ T cells, consistent with immune activation with PIT treatment. Applicant argues that these data show that PD-L1 targeted PIT ablates PD-L1 expressing cells in the tumor microenvironment unexpectedly reducing the growth of PD-L1 negative tumors.
Applicant argues that the treatment also elicits an immune memory response to treat distal tumors such as metastasized or distal, and/or heterologous tumors, referencing examples 3, 4, 6, 7, 13 and Figs. 2A-2B, 3A-3B, 5A-5F, 6A-6B, and 12.
Applicant’s arguments, however, are not persuasive.
The examples of the instant disclosure discuss the generation of an anti-PD-L1 antibody-IR700 conjugate (page 75, example 1) and describes a method in which IR700 is linked to the anti-PD-L1 antibody 10F.9G2, to produce an anti-PD-L1-IR700 conjugate (page 75, [0240]). This conjugate was used for the subsequent examples described in the disclosure.
Example 3 (page 77) describes a study of the inhibition of growth with a second tumor of the same type and discloses that mice that achieved CR from the treatment groups anti-PD-L1 conjugate with PIT treatment (at three light dose levels) and anti-PD-L1 conjugate alone, from Example 2, were implanted with a second tumor of the same type on day 56 post initial tumor implantation (page 77, [0250]). The example concludes that the growth of tumors was substantially reduced compared to naïve control mice (page 77, [0251]; figures 2A-B). It is noted that, in example 2, the mice were administered 100μg of the anti-PD-L1-IR700 conjugate and, twenty four hours after administration, tumors in the PIT group were illuminated at 690 nm and a dosage of 75, 100, or 150 J/cm2.
Example 4 which studied mice challenged with a third tumor of a different type, disclose that mice from example 3 that had achieved CR from the treatment groups anti-PD-L1-IR700 conjugate with PIT treatment (at all three light dose levels) and anti-PD-L1 conjugate alone, were implanted with a different type of tumor (page 77, example 4, [0254]; page 79, ). The study compared the anti-PD-L1-IR700 conjugate with illumination treatment to mice previously treated with anti-PD-L1-IR700 conjugate without light illumination and naïve controls (page 78, [0255]).
Example 6 studied anti-PD-L1-IR700 PIT delays or rejections of tumor growth in mice challenged with various types of tumors (page 79). In the study, mice were administered 100μg of the anti-PD-L1-IR700 conjugate and, twenty four hours after administration, tumors were illuminated at 690 nm and a dosage of 100 J/cm2 (page 79, [0260]). The example compares the treated mice with naïve controls (page [0261]).
Example 7 further challenged the mice from example 6 with a third tumor type (page 80) and compared the results to a control of naïve animals who were not previously treated (page 80, [0265]).
Example 8 demonstrates that the conjugate can inhibit growth of CT26 tumor cells with PD-L1 knockout. In the study 100μg of conjugate was administered as well as saline controls and tumors were illuminated at 690 nm and dosages of 75, 100, or 150 J/cm2. The example details that administration of the anti-PD-L1-IR700 conjugate and illumination (PIT) resulted in substantial tumor growth inhibition and increased survival compared to saline controls and conjugates without PIT. The example also discloses that administration of the conjugate alone without PIT also exhibited a reduction in tumor growth and increased survival compared to saline controls (Figs. 7B and C).
Example 9 demonstrates the effects on the conjugate with PIT in cell populations expressing PD-L1; example 10 demonstrates the recruitment of intratumoral neutrophils and examples 11 and 12 demonstrate that the conjugate with PIT activates the innate immune system. Example 13 demonstrate that the conjugate with PIT induces responses to distal tumors and example 14 demonstrates that the conjugate with PIT results in improved tumor burden reduction compared to multidosing of naked anti-PD-L1 antibody. Example 15 demonstrates that the conjugate and PIT reduces tumor burden in immunosuppressive murine tumor models.
In the examples of the instant disclosure, applicant compares outcomes of anti-PD-L1 PIT with results from controls treated with saline, anti-PDL1-IR700 without illumination, or naked anti-PD-L1 antibody (either as a single or multi dose regimen). These comparisons, however, are not a comparison to the closest prior art, for instance the method of Nagaya, in order to demonstrate that the result is unexpected or to demonstrate the criticality of the claimed elements.
MPEP 716.02 (b)(III) states “Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims.” MPEP 716.02 (e) states “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).”
Additionally, the results presented would have been expected in view of the teachings of the prior art. MPEP 716.02 states “Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected.”
An ordinarily skilled artisan would have reasonably expected the results presented in the instant disclosure based on the combined teachings of Nagaya and US’405 as well as Nagaya, US’405, and Tang. For instance, Nagaya demonstrates that anti-PD-L1-IR700 conjugates with NIR can be used to treat cancer and predicts that such conjugate could be used to treat cancers that are not responsive to anti-PD-L1 antibodies alone. US’405 also teaches the use of anti-PD-L1-IR700 conjugates in the treatment of cancers and suggests that one or more illuminations would be effective in treating cancers. US’405 also establishes that PD-L1 is expressed on immune cells in the tumor microenvironment and that such immune cells can be targeted with the conjugates. Tang teaches that, in PD-L1 negative tumors, immune cells in the tumor microenvironment can still effectively be targeted to treat the cancer. As such, one of ordinarily skilled artisan would have reasonably expected that the anti-PD-L1 conjugate with PIT studied by applicant would result in the outcomes that are demonstrated.
Furthermore, as discussed in detail in the rejection and response above, mechanistic outcomes demonstrated by applicant that would flow naturally from following the suggestions of the prior art cannot be the basis of patentability when the differences would have otherwise been obvious. Additionally, "The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.” See MPEP 2145 II.
Furthermore, even if the results presented were unexpected, which it is the Office’s position that they are not, the results are not commensurate in scope with the claimed invention. MPEP 716.02(d) states “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.”
The independent claims of the instant invention encompass any phthalocyanine dye linked to any targeting molecule that binds to PD-L1 at any concentration. The examples of the instant disclosure, which applicant argues results in unexpected outcomes, demonstrates only a single conjugate, specifically an antibody conjugate in which the phthalocyanine dye IR700 is linked to the anti-PD-L1 antibody 10F.9G2 and demonstrates the results at a single concentration of the conjugate, specifically 100 μg. The examples do not demonstrate that the supposedly unexpected property occurs over the full scope of the claimed invention and; therefore, the claims are not commensurate in scope with the results provided.
For these reasons, applicant’s arguments are not persuasive.
The following rejections are maintained or new.
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.
Copending application 17/469,804
Claims 1-6, 8, 10-12, 14, 19, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 209-230 and 232-234 of copending Application No. 17/469,804 in view of Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817, Tang, F. and P. Zheng (2018) Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci 8(34); 1-8, and US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018.
App’804 claims a phototoxic conjugate comprising at least one silicon phthalocyanine dye conjugated to a targeting molecule that binds PD-L1 (claim 209); wherein the targeting molecule that binds PD-L1 is an anti-PD-L1 antibody or antigen binding fragment thereof (claims 210 and 233) and is selected from among MDX-1105, MEDI4736, AMP224, BMS-936559, MPLDL3280A, MSB0010718C, and antigen binding fragments thereof (claims 211 and 234). App’804 claims that the silicon phthalocyanine dye is RI700 (claims 212-213 and 232). Further claimed is pharmaceutical compositions for treating a tumor comprising the conjugate an a pharmaceutically acceptable carrier (claim 214) and that the conjugate exhibits phototoxicity upon illumination to kill an immune cell expressing PD-L1 in the microenvironment of the tumor (claims 215 and 229). App’804 claims that the immune cell is a T cell, a B cell, a myeloid cell, or a macrophage (claims 216 and 230) and that the illumination enhances the immune response in a subject (claims 217 and 231). App’804 claims that the phototoxicity inhibits the growth of a tumor (claim 218).
App’804 further claims a method of treating a lesion comprising administering a conjugate comprising a silicon phthalocyanine dye conjugated to a PD-L1 targeting molecule and, after, irradiating the lesion at a wave length of 690±50 nm at a dose of at or about 50-100 J cm-2 or at or about 100 J/cm of fiber length, thereby treating the lesion (claim 219). App’804 claims that the irradiation is carried out between 30 minutes and 96 hours after administering the phototoxic conjugate, and 24 hours ± 3 hours after administration of the conjugate (claims 220-221). App’804 further claims that the wavelength is 690±20 nm (claim 222) and that the dose is at or about 50 J cm-2 or at or about 100 J/cm fiber length (claim 223). App’804 claims that the conjugate is administered intravenously or as an injection (claim 224). App’804 claims that the method of claim 219 can be repeated in a dosing schedule (claim 226) and that the dosing schedule is repeated if a residual lesion remains at a time that is more than or is about 2, 3, or 4 weeks, or 2 or 6 months, or 1 year after initiation of the prior administration of the conjugate (claim 226). App’804 claims that the irradiating step is carried out using a microlens-tipped fiber for surface illumination or using one or more cylindrical diffusing fibers (claim 227). App’804 claims that the lesion is associated with a disease selected from the group consisting of bladder cancer, stomach cancer, lung cancer, colon cancer, head and neck cancer, breast cancer, an endometrial cancer, and a pancreatic cancer (claim 228).
The claims of App’804 differ from those of the instant claims in that the claims of App’804 does not limit the tumor or lesion treated to comprising a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor or that the method results in the reduction or inhibition of the growth, size, or viability of the tumor or lesion. App’804 also does not claim that the tumor or lesion does not express PD-L1 or is a PD-L1 negative tumor, that the subject is naïve to treatment with a checkpoint inhibitor or that the method further comprises administering an additional agent.
The teachings of Nagaya, Tang, and US’405 are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of App’804 to treat a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor based on the teachings of Nagaya. A person of ordinary skill in the art would have been motivated to include treatment of this patient population in the methods of App’804 as Nagaya teaches that administration of an anti-PD-L1 IR700 conjugate could be successful in treating cancers that have not previously responded to the naked antibody alone. An ordinarily skilled artisan would have had a reasonable expectation of success as, like App’804, Nagaya teaches a method in which an anti-PD-L1 IR700 conjugate is administered to treat cancer followed by irradiation with the same wavelength and dose of the claims of App’804. One of ordinary skill in the art would reasonably expect that the method would result in rapid cell death in vitro and tumor growth reduction and survival improvement in vivo as Nagaya teaches such outcomes were observed with anti-PD-L1 IR700 conjugates.
It would have been prima facie obvious to one of ordinary skill in the art to apply the method methods of App’804 to treat tumor cells that do not express PD-L1, or comprises PD-L1 negative tumor cells, based on the teachings of Tang. It would have been obvious to treat tumor cells that are PD-L1 negative as Tang teaches that PD-L1 negative tumors have responded to PD-L1 blockade and that PD-L1 on either tumor cells or host immune cells contributes to tumor escape. As such, a person of ordinary skill in the art would reasonably expect that the anti-PD-L1 IR700 conjugate of App’804 would be capable of targeting PD-L1 expressing immune cells in PD-L1 negative tumors thereby treating the tumor. An outcome which is supported by Tang which teaches that even when PD-L1 knockout tumors were used, anti-PD-L1 therapy remained effective. Additionally, Tang teaches studies of cancers overlapping with the types of cancers claimed by App’804 for treatment with the conjugate.
It would have further been obvious to treat a subject who is naïve to treatment with an immune checkpoint inhibitor as US’405 teaches that methods using anti-PD-L1 IR700 conjugates can be used as an initial treatment for cancer, indicating that subjects who can be treated with conjugates such as those claimed by App’804 can include those who have not received any prior treatment, which would include a checkpoint inhibitor. An ordinarily skilled artisan would have been motivated to further administer an additional anti-cancer agent as US’405 teaches that additional agents can increase the killing of the tumor cells compared to cell killing in therapy methods using only the conjugate or methods involving a monotherapy with the immune modulating agent or anti-cancer agent alone. An ordinarily skilled artisan would reasonably expect that the method of App’804 would result in prolonged duration of remission based on the teachings of US’405 which teaches that administration of an anti-PD-L1 IR700 conjugate can increase survival indicators such as duration of median progression-free survival, duration of response, or median overall survival and that the treatment can result in complete remission (page 50, [0527]). An ordinarily skilled artisan would have had a reasonable expectation of success as both App’804 and US’405 teach anti-PD-L1 IR700 conjugates for the treatment of cancer. Additionally, the references teach overlapping cancers that can be treated by targeting PD-L1, such as lung cancer, melanoma, and lymphoma.
Regarding claims 6, 8, 10-12, and 38-39, the limitations recited in the claims are mechanistic outcomes that would flow naturally from the method claimed by App’804 in which PD-L1 expressing tumors are treated with an anti-PD-L1 IR700 conjugate followed by NAR light exposure. MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Additionally, these results would have been expected based on the teachings of Nagaya, Tang, and US’405 for the reasons discussed in detail in the rejections under 35 USC 103 above.
This is a provisional nonstatutory double patenting rejection.
Copending application 18/838,585
Claims 1-6, 8, 10-12, 14, 19, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-23, 25-27, 45, 52, and 64 of copending Application No. 18/838,585 in view of Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817, Tang, F. and P. Zheng (2018) Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci 8(34); 1-8, and US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018.
The claims of App’585 encompasses a conjugate comprising a PD-L1 antibody (the antibody of claim 1) and a heterologous molecule or moiety, where the heterologous molecule or moiety is a photoactivatable dye (claims 21-23 and 64). App’585 further claims that the photoactivatable dye is a Si-phthalocyanine dye, including IR700 (claims 26-27). App’585 claims a method of treating a tumor or lesion in a subject in need thereof comprising administering to the subject the conjugate and illuminating the area within the subject with a wavelength of between at or about 600 nm and at or about 850 nm, and at a dose of from or about 25 J/cm2 to at or about 400 J/cm2 or from at or about 2 J/cm fiber length to at or about 500 J/cm fiber length, thereby activating the conjugate; whereby the growth, volume or dimension of the tumor or lesion is reduced or inhibited (claim 45). App’585 further claims a method of immunizing a subject having a first tumor or lesion comprising the above method wherein the first tumor or lesion is inhibited in growth and/or reduced in size and the appearance, growth or establishment of one or more second tumors of lesions, located distally to the treated first tumor or lesion, is inhibited, delayed or prevented (claim 52).
The claims of App’585 differ from those of the instant claims in that the claims of App’585 does not limit the tumor or lesion treated to comprising a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor. App’585 also does not claim that the tumor or lesion does not express PD-L1 or is a PD-L1 negative tumor, that the subject is naïve to treatment with a checkpoint inhibitor or that the method further comprises administering an additional agent.
The teachings of Nagaya, Tang, and US’405 are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of App’585 to treat a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor based on the teachings of Nagaya. A person of ordinary skill in the art would have been motivated to include treatment of this patient population in the methods of App’585 as Nagaya teaches that administration of an anti-PD-L1 IR700 conjugate could be successful in treating cancers that have not previously responded to the naked antibody alone. An ordinarily skilled artisan would have had a reasonable expectation of success as, like App’585, Nagaya teaches a method in which an anti-PD-L1 IR700 conjugate is administered to treat cancer followed by irradiation with the same wavelength and dose of the claims of App’585.
It would have been prima facie obvious to one of ordinary skill in the art to apply the method methods of App’585 to treat tumor cells that do not express PD-L1, or comprises PD-L1 negative tumor cells, based on the teachings of Tang. It would have been obvious to treat tumor cells that are PD-L1 negative as Tang teaches that PD-L1 negative tumors have responded to PD-L1 blockade and that PD-L1 on either tumor cells or host immune cells contributes to tumor escape. As such, a person of ordinary skill in the art would reasonably expect that the anti-PD-L1 IR700 conjugate of App’585 would be capable of targeting PD-L1 expressing immune cells in PD-L1 negative tumors thereby treating the tumor. An outcome which is supported by Tang which teaches that even when PD-L1 knockout tumors were used, anti-PD-L1 therapy remained effective.
It would have further been obvious to treat a subject who is naïve to treatment with an immune checkpoint inhibitor as US’405 teaches that methods using anti-PD-L1 IR700 conjugates can be used as an initial treatment for cancer, indicating that subjects who can be treated with conjugates such as those claimed by App’585 can include those who have not received any prior treatment, which would include a checkpoint inhibitor. An ordinarily skilled artisan would have been motivated to further administer an additional anti-cancer agent as US’405 teaches that additional agents can increase the killing of the tumor cells compared to cell killing in therapy methods using only the conjugate or methods involving a monotherapy with the immune modulating agent or anti-cancer agent alone. An ordinarily skilled artisan would reasonably expect that the method of App’585 would result in prolonged duration of remission based on the teachings of US’405 which teaches that administration of an anti-PD-L1 IR700 conjugate can increase survival indicators such as duration of median progression-free survival, duration of response, or median overall survival and that the treatment can result in complete remission (page 50, [0527]). An ordinarily skilled artisan would have had a reasonable expectation of success as both App’585 and US’405 teach anti-PD-L1 IR700 conjugates for the treatment of cancer.
Regarding claims 6, 8, 10-12, and 38-39, the limitations recited in the claims are mechanistic outcomes that would flow naturally from the method claimed by App’585 in which tumors are treated with an anti-PD-L1 IR700 conjugate followed by NAR light exposure. MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Additionally, these results would have been expected based on the teachings of Nagaya, Tang, and US’405 for the reasons discussed in detail in the rejections under 35 USC 103 above.
This is a provisional nonstatutory double patenting rejection.
Copending application 17/638,147
Claims 1-6, 8, 10-12, 14, 19, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-9, 11, 16, 19-21, 23, 26, 34-36, 39, 42-43, 48, and 50 of copending Application No. 17/638,147 in view of US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018, Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817, and Tang, F. and P. Zheng (2018) Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci 8(34); 1-8.
App’147 claims a method of treating a tumor that is non-responsive to or resistant to a prior immune checkpoint inhibitor therapy comprising: (a) identifying a tumor or a lesion in a subject that is non-responsive or resistant to treatment with a prior immune checkpoint inhibitor; (b) administering to the subject a conjugate comprising a phthalocyanine dye linked to a targeting molecule that binds CTLA-4; (c) after administering the conjugate, illuminating the tumor or the lesion at a wavelength of at or about 600 nm to at or about 850 nm and at a dose of from at or about 25 J/cm2 to at or about 400 J/cm2 or from at or about 2 J/cm fiber length to at or about 500 J/cm fiber length; and (d) administering a first immune checkpoint inhibitor, wherein the tumor or lesion exhibits sensitivity to the first immune checkpoint inhibitor (claims 1-3, 19-20, 23, 26, 34-35). App’147 further claims that the prior immune checkpoint inhibitor comprises a PD-1, PD-L1, or CTLA-4 inhibitor (claims 8-9 and 21). App’147 further claims methods of provoking a systemic immune response in a subject using the conjugate and illumination (claims 11 and 16). App’147 claims that the method results in a response at a distal site to the illuminated tumor or lesion including an increase of CD8+ T cell infiltration or activation, an increase in the intratumoral CD8+:Treg ratio, an increase in intratumoral NK cell infiltration or activation, an increase in DC cell infiltration or activation, increased T cell priming, diversity, or an increase in one or more of a proinflammatory molecule, cytokine, or an immune cell activation marker (claims 36 and 39). App’147 further claims that the phthalocyanine dye is a Si-phthalocyanine dye and that the dye is IR700 (claims 42-43). App’147 claims that the conjugate administration is repeated one or more times (claim 48) and that the tumor or lesion is associated with a cancer selected from those recited, which include lung cancer, skin cancer, and lymphoma (claim 50).
The claims of App’147 differ from those of the instantly claimed invention in that the claims of App’147 comprise conjugates that target CTLA-4, not PD-L1. Additionally the claims of App’147 do not recite that the method results in the reduction or inhibition of the growth, size, or viability of the tumor or lesion. App’147 also does not claim that the tumor or lesion does not express PD-L1 or is a PD-L1 negative tumor, that the subject is naïve to treatment with a checkpoint inhibitor or that the method further comprises administering an additional agent.
The teachings of US’405 and Nagaya, and Tang are as discussed in detail above.
US’405 further teaches CTLA-4 as an alternative cell surface protein that can be targeted with IRDye 700DX (IR700) conjugates (page 6, [0065]). US’405 teaches that CTLA-4 is a co-inhibitory molecule that functions to regulate T-cell activation and is expressed exclusively on T-cells. CTLA-4 acts to inhibit T-cell activation and is reported to inhibit helper T-cell activity and enhance regulatory T cell immunosuppressive activity (page, [0477]).
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of App’147 to substitute the CTLA-4 binding molecule with an anti-PD-L1 binding molecule based on the teachings of US’405. It would have been obvious to make this substitution as US’405 teaches PD-L1 and CTLA-4 as alternative targeting molecules for conjugates with IR700 dyes in the treatment of cancer. This substitution is further supported by the teachings of Nagaya, which demonstrates that anti-PD-L1 IR700 conjugate are effective in treating cancer and could be effective in treating cancers that are not responsive to naked antibody alone. One of ordinary skill in the art would reasonably expect that the method would result in rapid cell death in vitro and tumor growth reduction and survival improvement in vivo as Nagaya teaches such outcomes were observed with anti-PD-L1 IR700 conjugates. An ordinarily skilled artisan would have had a reasonable expectation of success as App’147, US’405, and Nagaya all teach immune checkpoint targeting IR700 conjugates for the treatment of cancer. Additionally, the references teach overlapping cancers, such as lung cancer, skin cancer, and lymphoma.
It would have been prima facie obvious to one of ordinary skill in the art to apply the method methods of App’147 to treat tumor cells that do not express PD-L1, or comprises PD-L1 negative tumor cells, based on the teachings of Tang. It would have been obvious to treat tumor cells that are PD-L1 negative as Tang teaches that PD-L1 negative tumors have responded to PD-L1 blockade and that PD-L1 on either tumor cells or host immune cells contributes to tumor escape. As such, a person of ordinary skill in the art would reasonably expect that the anti-PD-L1 IR700 conjugate would be capable of targeting PD-L1 expressing immune cells in PD-L1 negative tumors thereby treating the tumor. An outcome which is supported by Tang which teaches that even when PD-L1 knockout tumors were used, anti-PD-L1 therapy remained effective. Additionally, Tang teaches studies of cancers overlapping with the types of cancers claimed by App’804 for treatment with the conjugate.
It would have further been obvious to treat a subject who is naïve to treatment with an immune checkpoint inhibitor as US’405 teaches that methods using anti-PD-L1 IR700 conjugates can be used as an initial treatment for cancer, indicating that subjects who can be treated with conjugates such as those claimed by App’804 can include those who have not received any prior treatment, which would include a checkpoint inhibitor. An ordinarily skilled artisan would have been motivated to further administer an additional anti-cancer agent as US’405 teaches that additional agents can increase the killing of the tumor cells compared to cell killing in therapy methods using only the conjugate or methods involving a monotherapy with the immune modulating agent or anti-cancer agent alone. An ordinarily skilled artisan would reasonably expect that the method would result in prolonged duration of remission based on the teachings of US’405 which teaches that administration of an anti-PD-L1 IR700 conjugate can increase survival indicators such as duration of median progression-free survival, duration of response, or median overall survival and that the treatment can result in complete remission (page 50, [0527]).
Regarding claims 6, 8, 10-12, and 38-39, the limitations recited in the claims are mechanistic outcomes that would flow naturally from the method in which PD-L1 expressing tumors are treated with an anti-PD-L1 IR700 conjugate followed by NAR light exposure. MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Additionally, these results would have been expected based on the teachings of Nagaya, Tang, and US’405 for the reasons discussed in detail in the rejections under 35 USC 103 above.
This is a provisional nonstatutory double patenting rejection.
Copending application 18/554,414
Claims 1-6, 8, 10-12, 14, 19, 21, 23-24, 29, 31, 34-35, 38-39, 43, 49-51, 55, and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 152-170 of copending Application No. 18/554,414 in view of Nagaya, T., et al (2017) Near infrared photoimmunotherapy with avelumab, an anti-programed death-ligand 1 (PD-L1) antibody Oncotarget 8(5); 8807-8817, Tang, F. and P. Zheng (2018) Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci 8(34); 1-8, and US 2018/0250405 A1 (Biel, M., et al) 6 SEPT 2018.
App’414 claims a conjugate comprising a silicon phthalocyanine dye covalently linked to a targeting molecule, where the dye has the recited structure. App’414 further claims that the targeting molecule binds to targets including PD-L1. App’414 claims a pharmaceutical composition comprising the conjugate as well as a method of treating a disease comprising administration of the conjugate and, after, illuminating a target region of the subject with an effective dose of light at a wavelength between 660 nm and 690 nm, and wherein the wavelength is 675 nm ± 10 nm. App’414 further claims that the condition is cancer selected from a group which overlaps with those of the instantly claimed invention. App’414 further claims administering an additional therapeutic agent.
The claims of App’414 differ from those of the instant claims in that the claims of App’414 does not limit the tumor or lesion treated to comprising a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor or the claimed dose. App’414 also does not claim that the tumor or lesion does not express PD-L1 or is a PD-L1 negative tumor, that the subject is naïve to treatment with a checkpoint inhibitor.
The teachings of Nagaya, Tang, and US’405 are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of App’414 to treat a tumor cell that is reduced in susceptibility to treatment with an immune checkpoint inhibitor and using the claimed dosages based on the teachings of Nagaya. A person of ordinary skill in the art would have been motivated to include treatment of this patient population in the methods of App’414 as Nagaya teaches that administration of an anti-PD-L1 IR700 conjugate could be successful in treating cancers that have not previously responded to the naked antibody alone. An ordinarily skilled artisan would have had a reasonable expectation of success as, like App’414, Nagaya teaches a method in which an anti-PD-L1 IR700 conjugate is administered to treat cancer followed by irradiation with the same wavelength of the claims of App’414.
It would have been prima facie obvious to one of ordinary skill in the art to apply the method methods of App’414 to treat tumor cells that do not express PD-L1, or comprises PD-L1 negative tumor cells, based on the teachings of Tang. It would have been obvious to treat tumor cells that are PD-L1 negative as Tang teaches that PD-L1 negative tumors have responded to PD-L1 blockade and that PD-L1 on either tumor cells or host immune cells contributes to tumor escape. As such, a person of ordinary skill in the art would reasonably expect that the anti-PD-L1 IR700 conjugate of App’414 would be capable of targeting PD-L1 expressing immune cells in PD-L1 negative tumors thereby treating the tumor. An outcome which is supported by Tang which teaches that even when PD-L1 knockout tumors were used, anti-PD-L1 therapy remained effective.
It would have further been obvious to treat a subject who is naïve to treatment with an immune checkpoint inhibitor as US’405 teaches that methods using anti-PD-L1 IR700 conjugates can be used as an initial treatment for cancer, indicating that subjects who can be treated with conjugates such as those claimed by App’414 can include those who have not received any prior treatment, which would include a checkpoint inhibitor. An ordinarily skilled artisan would have been motivated to further administer an additional anti-cancer agent as US’405 teaches that additional agents can increase the killing of the tumor cells compared to cell killing in therapy methods using only the conjugate or methods involving a monotherapy with the immune modulating agent or anti-cancer agent alone. An ordinarily skilled artisan would reasonably expect that the method of App’414 would result in prolonged duration of remission based on the teachings of US’405 which teaches that administration of an anti-PD-L1 IR700 conjugate can increase survival indicators such as duration of median progression-free survival, duration of response, or median overall survival and that the treatment can result in complete remission (page 50, [0527]). An ordinarily skilled artisan would have had a reasonable expectation of success as both App’414 and US’405 teach anti-PD-L1 silicon phthalocyanine dye conjugates for the treatment of cancer.
Regarding claims 6, 8, 10-12, and 38-39, the limitations recited in the claims are mechanistic outcomes that would flow naturally from the method claimed by App’414 in which tumors are treated with an anti-PD-L1 IR700 conjugate followed by NAR light exposure. MPEP 2145 II. states “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” The MPEP section further states “The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”
Additionally, these results would have been expected based on the teachings of Nagaya, Tang, and US’405 for the reasons discussed in detail in the rejections under 35 USC 103 above.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the arguments filed 02/25/2026, applicant requests that the provisional double patenting rejections be held in abeyance and that the rejection will be further considered at the identification of allowable subject matter.
As no allowable subject matter is identified, the provisional double patenting rejections are maintained.
Conclusion
No claims are allowed.
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/AUDREY L BUTTICE/Examiner, Art Unit 1647
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693