DETAILED ACTION
Claims 16-21, 26, 28 and 30 are currently pending. Claims 16-20, 28 and 30 are currently under examination.
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 of radiation, treatment is for tumor/lesion, anti-PD-1 inhibitor and head and neck squamous cell carcinoma in the reply filed on 04/17/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 21 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/17/2026.
Priority
The instant application is a national stage entry of PCT/EP2021/079399, filed 10/22/2021, which claims priority to EP20306326.8, filed 11/05/2020.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 05/04/2023, 06/03/2025 AND 11/20/2025 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Claim Interpretation
Claims 16 and 18 contains the limitation of tumor/lesion, wherein the “/” will be interpreted as “and/or”.
Claim Objections
Claim 30 is objected to because of the following informalities: Claim 30 contains the limitation “nanoparticles as are administered in the form…” which appears to be a typographical error for “nanoparticles are administered in the form”.. Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16-20, 28 and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the limitation "the nanoparticles and/or aggregates of nanoparticles". There is insufficient antecedent basis for this limitation in the claim. Claims 17-20, 28 and 30 are further rejected as not curing the ambiguity of claim 16.
Claim 28, the limitation of (squamous) non-small cell lung cancer, (metastatic) small cell lung cancer and (metastatic) head and neck squamous cell cancer it is unclear if the limitations in the parenthesis is optional or required, thus leading to unclear metes and bounds of the instant claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 16-20, 28 and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/189125 (IDS dated 05/04/2023) in view of US 2009/0285783 and Mooradian.
Regarding claims 16 and 30, the limitation of a method of treating a solid tumor cancer in a human patient and has a clinical staging of 1-5 metastasis, irrespective of the level of control of a previously treated primary tumor, wherein the nanoparticle and/or aggregation of nanoparticles are selected from a group which includes hafnium oxide and the method comprises administering the nanoparticles to at least one metastasis in the patient and exposing the patient who has been administered with the nanoparticles to ionizing radiation and administering at least one IO agent selected from an anti-PD-1 inhibitor is met by the ‘125 publication teaching nanoparticles for use as a therapeutic vaccine in the context of radiotherapy in a subject suffering of a cancer, in particular of metastatic cancer (abstract). The subject is suffering from a metastatic cancer and undergoing a palliative radiotherapy and subject suffering from metastatic cancer for whom curative radiotherapy has been abandoned or not conventionally treated by radiotherapy (page 1, lines 15-20). The combination of nanoparticles with radio therapy significantly enhances the host’s anti-cancer immune response and optimizes the global treatment (page 4, lines 5-15). Radiotherapy may help reverse the tolerance to weakly immunogenic tumor associated antigens in order to elicit an anticancer immune response (page 4, lines 15-20). The metastases are taught to be typically more than 5 (page 9, first paragraph). Cancer is taught to include head and neck cancer (page 10, lines 1-10). The nanoparticle is taught to include hafnium oxide (page 13, lines 25-35, Example 1). The nanoparticle may further include a targeting agent (page 15, second paragraph) and at least one immunotherapeutic agent (page 16, lines 30-36) such as anti-PD-1 agents (page 17, lines 5-10). The nanoparticles are contacted with the cancel cells before radiotherapy including directly into tumor bed after resection surgery or tumor metastases (page 19, first paragraph) wherein nanoparticle and immunotherapeutic agent can be administered simultaneously or separately (page 19, lines 15-20) and ionizing radiation is used (page 10, lines 25-35).
Regarding claim 17, the limitation of wherein the at least one IO agent administered is an anti-PD-1 inhibitor is met by the ‘125 publication teaching at least one immunotherapeutic agent (page 16, lines 30-36) such as anti-PD-1 agents (page 17, lines 5-10).
Regarding claim 18, the limitation of wherein the nanoparticles are administered to only one tumor/lesion or metastasis is met by the ‘125 publication teaching treatment of tumor metastase(s) (page 19, lines 1-10).
Regarding claim 19, the limitation of wherein the human patient has had a previous anticancer treatment involving radiotherapy and at a clinic staging has at least one LR tumor in a previously irradiated site is met by the ‘125 publication teaching palliative radiotherapy may also be used to assist with maintenance of local tumor control in area likely to be affected and become symptomatic (page 2, lines 30-35).
Regarding claims 20 and 28, the limitation of wherein the LRR tumor is a head and neck squamous cell carcinoma is met by the ‘125 publication teaching cancer is taught to include head and neck cancer (page 10, lines 1-10) and includes squamous cell carcinoma (page 9, lines 25-35).
The ‘125 publication does not specifically teach “for whom administration of an immune-oncology (IO) agent is not indicated as monotherapy because of low tumor cell expression levels of biomarkers in the biological pathway targeted by said IO agent” (claim 1).
The ‘783 publication teaches although a single treatment modality such as radiation therapy, chemotherapy or immunotherapy can result in improvement of a patient, superior results can be achieved when such modalities are used in combination. In particular combination of radiotherapy which can be directed to a localized area containing a tumor and immunotherapy which provide a systemic mode of treatment ([0005], [0022]).
Mooradian teaches what to do when anti-PD-1 therapy fails in patients with melanoma (title). Monotherapy with immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma with 40% of patients achieve partial or complete response. A subset of patients who initially respond to therapy will progress leaving the majority of patients in need of an effective second-line approach to overcome primary or acquired resistance (page 1). Loss of T-cell function through expression of alternative immune checkpoints is taught as either primary are acquired resistance to include PD-1 inhibition (page 2, first paragraph). Recent studies have shown favorable cancer related outcomes (e.g. reduced size of brain metastases and decreased number of new lesions) in patients who received ration in combination with immune checkpoint inhibitor therapy compared with patients who received radiation alone (page 4, second paragraph). Radiation therapy provides not only the ability to palliate symptoms but also to eradicate a resistant subclone when used at definitive dose. One appealing benefit of radiation therapy is its theoretical ability to modulate an immune response and thereby synergize an anticancer effect when used concurrently with immune checkpoint inhibitor therapy. Local radiation therapy is associated with regression of metastatic sties distant from the radiated site has been reported in patients treated with both radiation therapy and immune checkpoint inhibitor therapy (page 4, first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of hafnium oxide nanoparticles and anti-PD-1 inhibitor to treat recurrent cancer and metastases as the ‘125 publication teaches the use of hafnium oxide nanoparticles for radiation treatment and anti-PD-1 inhibitors to be used in combination for maintenance of local tumors and to treat metastases. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use the combination of radiation nanoparticles and anti-PD-1 inhibitors as Mooradian teaches the combination of radiation therapy modulates the immune response to immunotherapy agents, wherein patients are known to have primary or acquired resistance to immunotherapy. Thus it would have been prima facie obvious to one of ordinary skill in the art to use a combination of immunotherapy and radiation particles as a secondary treatment. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ’783 publication teaches combination of radiotherapy and immunotherapy and the ‘125 publication and Mooradian are both directed to metastases including brain.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
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