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 of Species
Applicant’s election of species of Ir(III)-BZQ is acknowledged. As applicant did not specify if the election was with or without traverse, the examiner is considering the election to be without traverse. No prior art was found against the elected species. The search was therefore expanded to the next species. The expansion to the next species. The expansion is not an indication that the entire scope of the claims have been examined.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5,7 and 9-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5,7 and 9-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The claims are directed to a process of treating a cancer patient. However, treating cancer is difficult, and methods and protocols that treat one form of cancer do not necessarily treat a representative number of cancers under the term cancer. For example, the application does not disclose how cancers that do not have tumors, such as Leukemia, Multiple Myeloma, and lymphoma, can be treated by the present method, and for his reason, there is insufficient written description in the application to treat cancer patient across the scope of the claimed “cancer.”
Claim Rejections - 35 USC § 112
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 1-5,7 and 9-18 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 1 recites a “process of treating a cancer patient.” It’s unclear if the claim is directed to treating cancer, or treating any condition or ailment in a cancer patient. Further claim 1 recites “wherein an amount of tissue excised is based on identifying cellular uptake of the iridium-containing nucleoside from the medical image. It’s unclear what it means to base an amount of tissue excised on identifying cellular uptake of the iridium-containing nucleoside and what criteria in the said identifying are used to base the amount of tissue excised. Further regarding claims 4 and 17, it’s unclear what it means to obtain a medical image by “providing real-time information simultaneously.” Although the claim recites “by combining color reflectance images with fluorescence emission from the iridium-containing nucleoside,” it’s unclear how this provides real-time information and what information is provided.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1-5,7 and 9-18 are rejected under 35 U.S.C. § 103 as being unpatentable over US 10231626 to Steinbach in view of Jones (Journal of Bioimaging, 2021, Vol. 14, pp. 45–52) in further view of Volpi ("A novel multiwavelength fluorescence image-guided surgery device," Proceedings of SPIE, 2014).
Steinbach teaches a treating a cancer patient by administering an imaging agent, obtaining a medical image of the patient, and excising a tumor and a tumor margin from the patient, wherein the amount of tissue excised is based on identifying cellular uptake of the agent from the medical image (Fluorescence-Guided Surgery). Steinbach utilizes indocyanine green (ICG) as the targeting agent ( III Fluroecsent “Visual Enhancers” and “Smart Probes” for surgery). Cancers contemplated include brain, breast, and ovarian cancers (Probes). Steinbach teaches local and IV administration (claims; Figures 9 and 11),
Steinbach fails to teach wherein the agent is an iridium-containing nucleoside.
Jones teaches the synthesis and cellular uptake of cyclometalated iridium(III)-containing nucleoside complexes specifically designed for targeting rapidly proliferating cancer cells and performing optical/phosphorescence bioimaging to identify tumor boundaries (abstract; Experimental Section).
Volpi teaches an established medical framework for fluorescence-guided surgery (FGS). Volpi teaches a surgical process wherein a tumor and a surrounding tumor margin are excised from a patient, and wherein the amount of tissue excised is strictly based on identifying cellular uptake of a fluorescent tracer from a real-time medical image to ensure clear surgical margins (Abstract; Introduction; Experimental Section).
It would have been obvious to substitute the fluorescent dye of Steinbach with the iridium-containing nucleoside complex taught by Jones. The motivation for this substitution would be to exploit the superior photostability and predictable metabolic DNA-targeting pathways of iridium-nucleoside conjugates to improve tumor margin clarity during surgical excision. Swapping a systemic delivery route for a localized delivery route is a routine optimization well within the capability of the artisan. Regarding claim 4, Steinbach teaches an optical imaging apparatus that uses split-path sensors to simultaneously capture white-light color reflectance and near-infrared fluorescent emission, overlaying them onto a single real-time display monitor. The hardware setup is identical, and substituting one light-emitting compound for another on a standard overlay imaging device relies entirely on predictable technological principles.
Volpi teaches a fluorescence-guided surgery layout where the optical capturing step and the tissue cutting step ("excising") happen simultaneously in real time during a surgical operation. Volpi teaches that the imaging sensor streams continuous visual data directly onto the active surgical field so the surgeon adjusts the blade paths on the fly. It would have been obvious to facilitate dynamic intraoperative decisions, minimizing time under anesthesia. Regarding the obtaining being performed from about 4 to about 24 hours after administering the iridium-containing nucleoside, the designated timeframe of 4 to 24 hours post-injection represents a standard metabolic clearance window for small-molecule metabolic labels. Prior art in oncology heavily documents that small-molecule nucleoside analogs require a multi-hour window (typically 4–12 hours) to yield high tumor-to-background contrast ratios. This allows the circulatory system to clear unbound background tracer while the rapidly dividing malignant cells metabolize, accumulate, and lock the tracer into their DNA/RNA structures. Choosing a standard 4-to-24-hour pharmacokinetic delay to image an injected tracer is a routine optimization problem within the capabilities of the artisan looking to enhance signal clarity during tumor resections. Lo teaches modifying and conjugating various fundamental biomolecules, including structural nucleic acid components, to a cyclometalated iridium(III) core to exploit tumor proliferation. Furthermore, using structural analogs of deoxyadenosine to target rapidly dividing cancer cell lines via DNA synthesis pathways was universally well known prior to 2022, the artisan would select a deoxyadenosine framework to serve as the nucleoside carrier because malignant tumors overexpress nucleotide transporters, ensuring massive, targeted cellular uptake of the tracking agent. Lo explicitly lists major aggressive malignancies—including brain, breast, and ovarian cancers—as primary diagnostic and therapeutic targets for organometallic complexes. Furthermore, Volpi teaches general clinical surgical literature teach that these specific solid tumors are prime candidates for fluorescence-guided surgery because they have infiltrative margins that are incredibly difficult to distinguish from healthy brain, breast, or pelvic tissues with the naked eye. Specifying these specific tumor types represents a routine application of the disclosed method to the exact clinical pathologies that suffer from high rates of recurrence due to positive surgical margins (Abstract; Introduction; Experimental Section).
Notes and Comments
Claim 19 is objected to as being dependent on a no-allowed claim, but would otherwise be allowable if written in independent format.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618
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