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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 30 April 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without specifying traverse of chlorotoxin as the species of targeting agent, chitosan-PEG copolymer as the species of biocompatible coating, and brain tumor as the species of cancer to be treated in the reply filed on 22 June 2026 is acknowledged.
Upon further search and consideration, art was found that reads on lung cancer as the species of cancer to be treated. As such, lung cancer alone is rejoined and examined together. The election of species requirement is maintained to the extent that the species do not make a contribution over the prior art.
Claims 1-17 are examined on the merits herein.
Claim Objections
Applicant is advised that should claim 5 be found allowable, claim 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 5 recites the method of claim 3, wherein the targeting agent selectively delivers the iron oxide nanoparticle to the site, which is defined in claim 3 as being a cancerous tumor. As such, claim 5 and claim 7 both cover the content of the targeting agent selectively delivering the iron oxide nanoparticle to the cancerous tumor.
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.
Claims 1-4, 8, 12, 14, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Hauser et al. (Biomaterials, 2016, Vol. 105, 127-135 cited on Applicant’s IDS filed 30 April 2025) in view of Klein et al. (J Phys Chem B, 2014, Vol. 118, 6159-6166 cited on Applicant’s IDS filed 30 April 2025) as evidenced by Coulter et al. (Clinical Oncology, 2013, Vol. 25, 593-603 cited on Applicant’s IDS filed 30 April 2025).
Claim 1 is drawn to a method for targeted radiation therapy in a subject, comprising:
administering to a subject an iron oxide nanoparticle having an iron oxide core, a biocompatible coating surrounding the core, and a targeting agent associated with the coating, to provide a site in the subject having accumulated iron oxide nanoparticles; and
applying γ- and/or x-ray irradiation to the subject at the site having accumulated iron oxide nanoparticles to produce photoelectrons at the site.
Claim 2 is drawn to a method for producing photoelectrons at a select site in a subject, comprising the same steps (a) and (b) of claim 1.
Claim 3 is drawn to a method for treating a cancer in a subject, comprising the same steps (a) and (b) of claim 1, wherein the site is a cancerous tumor.
Claim 8 is drawn to the method of claim 3, wherein the cancerous tumor is a solid tumor.
Claim 12 is drawn to the method of claim 3, wherein the cancerous tumor is a tumor of the lung.
Hauser et al. teach a targeted method for enhanced radiation therapy (Title) for the treatment of cancer (Pg. 128 left column second paragraph), additionally teaching radiation therapy causing electrons to leak from the electron transport chain (Abstract) i.e., production of photoelectrons. Hauser et al. teach the method comprising administering iron oxide nanoparticles coated in dextran and conjugated to TAT followed by applying radiation (Sections 2.2-2.6 and 2.10), wherein the site is A549 lung carcinoma cells. Hauser et al. further teach TAT as a targeting moiety (Pg. 128 right column first paragraph).
As such, Hauser et al. teach a method for targeted radiation therapy, producing photoelectrons, and treating cancer, comprising (a) administering to a subject an iron oxide nanoparticle having an iron oxide core, a biocompatible coating surrounding the core, and a targeting agent associated with the coating, to provide a site in the subject having accumulated iron oxide nanoparticles; and (b) applying irradiation to the subject at the site having accumulated iron oxide nanoparticles to produce photoelectrons at the site, wherein the site is a solid lung cancer tumor.
The method of Hauser et al. differs from the instantly claimed method in the following way:
Hauser et al. are silent as to the type of radiation applied.
Yet, as to 1: Klein et al. also teach a method of treating cancer tumors by applying radiation to a site having an accumulation of iron oxide nanoparticles, further teaching the radiation being x-ray irradiation (Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Hauser et al. to utilize x-ray irradiation as taught by Klein et al. It would have been obvious to substitute one type of radiation suitable for cancer radiotherapy for another to obtain the predictable result of a targeted iron oxide enhanced radiation method for treating cancer, with a reasonable expectation of success.
Based on all of the foregoing, claims 1-3, 8, and 12 are rejected as prima facie obvious.
Claim 4 is drawn to the method of claim 3, wherein the photoelectrons are Auger photoelectrons.
Hauser et al. do not teach the photoelectrons being Auger photoelectrons.
However, as evidenced by Coulter et al. the irradiation of metallic nanoparticles with ionizing radiation leads to the emission of Auger electrons (“Physiochemical Mode of Action” on pg. 539).
As Hauser et al. and Klein et al. teach the irradiation of the instantly claimed metallic nanoparticles with ionizing radiation, the instantly claimed emission of Auger photoelectrons is necessarily present.
As such, claim 4 is rejected as prima facie obvious.
Claim 14 is drawn to the method of claim 3, wherein the iron oxide core comprises magnetite.
Hauser et al. further teach the iron oxide nanoparticles comprising Fe3O4 (Sec. 2.2), further teaching Fe3O4 as magnetite (Pg. 128 left column second paragraph).
As such, claim 14 is rejected as prima facie obvious.
Claim 17 is drawn to the method of claim 3, wherein the nanoparticle has a diameter from about 5 to about 200 nm.
Hauser et al. further teach the nanoparticles having a diameter of 127 nm (pg. 131 left column third paragraph).
As such, claim 17 is rejected as prima facie obvious.
Claims 5-7, 9-11, 13, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Hauser et al. and Klein et al. as applied to claims 1-4, 8, 12, 14, and 17 above, and further in view of Veiseh et al. (Cancer Res, 2009, Vol. 69, 6200-6207 cited on Applicant’s IDS filed 30 April 2025).
The teachings of Hauser et al. and Klein et al. have been set forth above.
Claim 5 is drawn to the method of claim 3, wherein the targeting agent selectively delivers the iron oxide nanoparticle to the site.
Claim 6 is drawn to the method of claim 3, wherein the targeting agent is chlorotoxin (Applicant’s elected species).
Claim 7 is drawn to the method of claim 3, wherein the targeting agent selectively delivers the iron oxide nanoparticle to the cancerous tumor.
Claim 9 is drawn to the method of claim 3, wherein the cancerous tumor is a brain tumor of any pathology.
Claim 10 is drawn to the method of claim 3, wherein the cancerous tumor is a primary brain tumor.
Claim 11 is drawn to the method of claim 3, wherein the cancerous tumor is a neuroectodermal tumor.
The method of Hauser et al. and Klein et al. differs from the instantly claimed method in the following ways:
Hauser et al. and Klein et al. are silent as to the selective delivery of the nanoparticle to the site; and
Hauser et al. and Klein et al. do not teach the targeting agent comprising chlorotoxin.
Yet, as to 1: Klein et al. further teach iron oxide nanoparticle enhanced radiation therapy as being suitable for treating breast cancer and colon cancer (“Cell Culture” on pg. 6161 and “Conclusion” on pg. 6165).
As Hauser et al. teach treatment of lung cancer and Klein et al. teach treatment of breast cancer and colon cancer, the prior art indicates that this method of treatment is suitable for applying to a number of different cancer types.
Veiseh et al. teach polymer coated iron oxide nanoparticles with a conjugated targeting agent (Fig. 1) for specific targeting of brain tumors (Title) Veiseh et al. further teach CTX (chlorotoxin) as a tumor-targeting ligand with strong affinity to neuroectodermal tumors, glioma, and medulloblastoma (Pg. 6201 left column).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Hauser et al. and Klein et al. by using chlorotoxin as the targeting agent as taught by Veiseh et al. It would have been obvious to substitute one targeting agent suitable for use with polymer coated iron oxide nanoparticles to obtain the predictable result of a method for treating neuroectodermal tumors, glioma, and medulloblastoma with selectively targeting iron nanoparticles, with a reasonable expectation of success.
As such, claims 5-7 and 9-11 are rejected as prima facie obvious.
Claim 13 is drawn to the method of claim 3, wherein the iron oxide nanoparticle is administered to the subject intravenously.
Hauser et al. and Klein et al. do not teach administering the iron oxide nanoparticle intravenously.
However, Veiseh et al. teach administering the iron oxide nanoparticles intravenously (“Animal Model” on pg. 6202).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Hauser et al. and Klein et al. to include a step of administering the nanoparticles intravenously as taught by Veiseh et al. It would have been obvious to substitute one method for administering targeted iron nanoparticles to a subject for another to obtain the predictable result of a targeted method for treating cancer, with a reasonable expectation of success.
As such, claim 13 is rejected as prima facie obvious.
Claim 15 is drawn to the method of claim 3, wherein the coating is effective to disperse the iron oxide nanoparticles and have thicknesses in the range from about 1 to about 100 nm.
Hauser et al. further teach the coated nanoparticles forming an aqueous suspension (Sec. 2.6 on pg. 129), indicating that the coating is effective to disperse the iron oxide nanoparticles.
Hauser et al. are silent as to the thickness of the coating.
However, Veiseh et al. teach iron oxide nanoparticles having a polymer coating wherein the coating is about 13nm thick (Pg. 6202 right column last paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticles of Hauser et al. to have a 13nm thick coating as taught by Veiseh et al. It would have been obvious to combine the known polymer coated iron oxide nanoparticles with the known thickness of a polymer coating for iron oxide nanoparticles to yield the predictable result of a sufficiently coated iron oxide nanoparticle, with a reasonable expectation of success.
As such, claim 15 is rejected as prima facie obvious.
Claim 16 is drawn to the method of claim 3, wherein the coating comprises a chitosan-PEG copolymer layer (Applicant’s elected species).
Hauser et al. do not teach a chitosan-PEG copolymer coating.
However, Veiseh et al. teach chitosan-PEG copolymer as a suitable coating material for iron oxide nanoparticles grafted to targeting agents (Pg. 6202 left column pars. 1-3).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the nanoparticles of Hauser et al. by using a coating comprising a chitosan-PEG copolymer coating as taught by Veiseh et al. It would have been obvious to substitute one polymeric coating suitable for forming targeted iron oxide nanoparticles for another to obtain the predictable result of a polymer coated targeted iron oxide nanoparticle, with a reasonable expectation of success.
As such, claim 16 is rejected as prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Hoerner whose telephone number is (571)270-0259. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm eastern.
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/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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