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 statement filed on January 16, 2024 is acknowledged and has been considered by the examiner.
Drawings
The drawings are objected to for the following reasons:
Figures 3-6 are not readily interpretable in their current state. All such figures are associated with a gradient color scale intended to communicate the intensity of a measured value from low to high. However, the examiner is unable to interpret the meaning of dark colored regions of the figures as presented. In the current format, the color scales indicate that dark colors correspond to both high and low intensity values and light colors correspond to moderate and very high intensity values.
Appropriate correction is required.
Specification
The abstract of the disclosure is objected to because it is too short in length (24 words). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 7 is objected to because of the following informality: “Wherein systemic administration” should be revised to “wherein the systemic administration” to clarify meaning. Appropriate correction is required.
Claims 9-16 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim Interpretation
The examiner interprets claims 4-8 to contain functional language. Claims 4 and 5 are drawn to the chemical compound 5-aminolevulinate or a derivative thereof. Claims 6-8 include the compound 5-aminolevulinate in their scopes. In claim 4, “for use in (a method of) surgery on a subject” is interpreted to describe the intended use of the chemical compound. No further structural restrictions are provided for the composition of matter. The additional limitations of claims 5-8 are interpreted to only narrow the scope of the intended use (for the embodiments drawn to the composition of matter in claims 6-8). Please note that a recitation of intended use does not distinguish a composition of matter claim over the prior art since a composition claim covers what the composition is and not what it is used for. A chemical composition and its properties are inseparable (MPEE § 2112.01). Therefore, as long as the prior art teaches the claimed structural features of the composition, it reads on the claim.
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 1-16 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.
Regarding claims 1-16, the scope of “5-aminolevulinate or a derivative thereof” is unclear. It is not clear to what extent of modification the compound may be modified while still qualifying as such a derivative. Therefore, the claims are considered indefinite.
Regarding claim 6, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of examination, the examiner will interpret the scope of the claim to include all modes of systemic administration. Furthermore, claim 7 is rejected due to its dependence on claim 6.
Regarding claims 6-8, the current language claims both a process (method of using 5-aminolevulinate) and a product (5-aminolevulinate itself). Per MPEP § 2173.05(p)(II), a single claim which claims both a product and the method steps of using the product is indefinite. Furthermore, the claims that depend from each of these claims are rejected for said dependence. For the purpose of examination, as it is unclear which invention is being claimed, in pursuit of compact prosecution, the examiner has examined these claims as both products and methods of use.
Regarding claims 9-12 and 14-16, the current language claims both a process (method of using 5-aminolevulinate) and a product (5-aminolevulinate itself). Per MPEP § 2173.05(p)(II), a single claim which claims both a product and the method steps of using the product is indefinite. Furthermore, the claims that depend from each of these claims are rejected for said dependence.
Regarding claims 9-16, these claims are multiple dependent claims that depend on multiple dependent claims. Therefore, it is not clear what the scope of the claimed embodiment for each of these claims. This ambiguity renders these claims indefinite. Furthermore, the claims that depend from each of these claims are rejected for said dependence.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 4-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (a product of nature) without significantly more. The claims recite "[a/the] 5-aminolevulinate or a derivative thereof," and 5-aminolevulinate is a naturally occurring amino acid in the human body. This judicial exception is not integrated into a practical application because the scope of the claims include just 5-aminolevulinate itself without any additional elements. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the current scope of the claims includes embodiments in which no additional elements are required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 4-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Millesi (Millesi, M.; et al., Neurosurg. Focus, 2014).
Millesi teaches the use of 5-aminolevulinic acid in fluorescence guided neurosurgery (pg. 1, Abstract). This method requires the use of 5-aminolevulinic acid, which is also known as 5-ALA and 5-aminolevulinate. Claims 4 and 5 are drawn to 5-aminolevulinate and claims 6-8 include within their scopes embodiments that are drawn to 5-aminolevulinate. Therefore, the disclosure of 5-aminolevulinic acid by Millesi anticipates claims 4-8.
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 1-3 and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Pedro (Pedro, M.T.; et al., Front. Oncol., 2021) in view of Millesi (Millesi, M.; et al., Neurosurg. Focus, 2014).
Pedro teaches a method of fluorescence guided surgery of malignant peripheral nerve sheath tumors (pg. 1, Abstract). More specifically, the method of Pedro uses sodium fluorescein as the fluorescent agent for the fluorescence-guided surgery (pg. 2, Study Group, Dosage, and Technical Equipment). The sodium fluorescein was administered intravenously during anesthesia (pg. 2, Study Group, Dosage, and Technical Equipment). In the cases of malignant peripheral nerve sheath tumors, the affected nerves were the cutaneous nerve paraspinal and the ulnar nerve (pg. 2, Table 1). Pedro teaches that the surgeon’s opinion of the use of fluorescence guided surgery for malignant peripheral nerve sheath tumors was that it was very useful (pg. 2, Table 1). The surgery involved detecting fluorescence emitted by the peripheral nerve of the subject in order to visualize the peripheral nerve, and specifically to identify tumor cells (pg. 6, Figure 7).
Pedro does not teach performing fluorescence guided surgery on a peripheral nerve using 5-aminolevulinate or a derivative thereof.
Millesi teaches fluorescence guided surgery of spinal tumors using 5-aminolevulinic acid to generate the protophorphyrin IX (PpIX) fluorophore (pg. 1, Abstract). Millesi explains that intraoperative visualization through means like fluorescence guided surgery can reduce subtotal resection of tumors, which should reduce the recurrence of such tumors (pg. 2, left column, first paragraph). Millesi also teaches that 5-aminolevulinic acid (also known as 5-ALA and 5-aminolevulinate) is already used for fluorescence guided resection of malignant gliomas in the brain and results in increased rates of complete resections (pg. 2, left column, second paragraph). Millesi also explains that 5-ALA has been used for fluorescence guided neurosurgery of tumors since 1998 (pg. 5, Fluorescence-Guided Procedures With 5-ALA in Neurosurgery). In the method of Millesi, 5-ALA was administered orally 3 hours before induction of anesthesia, spinal tumors were visualized by detecting PpIX fluorescence, and surgery was performed (pg. 2, 5-ALA in Spinal Tumor Surgery). Millesi used violet-blue excitation light to generate the PpIX fluorescence signal (pg. 3, Intraoperative PpIX Fluorescence Characteristics of Spinal Tumors, first paragraph). Millesi teaches that PpIX fluorescence is a powerful tool for detecting residual tumor tissue in certain tumors (pg. 5, Discussion, first paragraph).
A person of ordinary skill in the art would have recognized that both Pedro and Millesi teach means of fluorescence-guided surgery of neurological tumors and that the use of the fluorophore enables improved identification of tumor cells and therefore improved tumor resection. It would be recognized that both sodium fluorescein and 5-ALA-induced PpIX are known fluorescence agents in neurosurgery and that both serve the same functions. Therefore, it would be recognized that one could be substituted for the other and predictable results would be achieved (MPEP § 2144(I)(B)).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of fluorescence-guided malignant peripheral nerve sheath tumors taught by Pedro by substituting the fluorescein fluorophore with administration of 5-ALA and the subsequent production of PpIX, as taught by Millesi. This would result in the predictable result of an alternative means of fluorescence guided surgery of neurological tumors.
Regarding claim 1, the method of Pedro involves detection of fluorescence of a peripheral nerve using fluorescein and a fluorescence microscope (pg. 2, Study Group, Dosage, and Technical Equipment; and pg. 8, Figure 7). To acquire the fluorescence image, the nerve is exposed to light and fluorescence is detected, enabling visualization of the nerve and the tumor cells. The 5-ALA-based method of Millesi involves the oral administration of 5-ALA 3 hours prior to induction of anesthesia, followed by acquiring fluorescence images during the surgery (pg. 2, 5-ALA in Spinal Tumor Surgery). The 5-ALA is administered orally, which is a form of systemic administration allowing the 5-ALA to travel throughout the body, including allowing it to contact nerves. The acquisition of the fluorescence images involves exposing the nerve to light at least 3 hours after administration of 5-ALA and detecting fluorescence emitted by the nerves being visualized. Therefore, the combined teachings of Pedro and Millesi render claim 1 obvious.
Regarding claim 2, the method of Pedro involves detection of fluorescence of a peripheral nerve using fluorescein and a fluorescence microscope (pg. 2, Study Group, Dosage, and Technical Equipment; and pg. 8, Figure 7). To acquire the fluorescence image, the peripheral nerve is exposed to light. The 5-ALA-based method of Millesi involves the oral administration of 5-ALA 3 hours prior to induction of anesthesia, followed by acquiring fluorescence images during the surgery (pg. 2, 5-ALA in Spinal Tumor Surgery). The 5-ALA is administered orally, which is a form of systemic administration allowing the 5-ALA to travel throughout the body, including allowing it to contact nerves. The acquisition of the fluorescence images involves exposing the nerve to light at least 3 hours after administration of 5-ALA. Therefore, the combined teachings of Pedro and Millesi render claim 2 obvious.
Regarding claim 3, the method of Pedro involves detection of fluorescence of a peripheral nerve using fluorescein and a fluorescence microscope (pg. 2, Study Group, Dosage, and Technical Equipment; and pg. 8, Figure 7). To acquire the fluorescence image, the nerve is exposed to light and fluorescence is detected, enabling visualization of the nerve and the tumor cells. Surgery was performed on patient no. 8 while visualizing the peripheral nerve using fluorescence to enable a complete resection of the tumor (pg. 8-9, Illustrative Cases, second paragraph). The 5-ALA-based method of Millesi involves the oral administration of 5-ALA 3 hours prior to induction of anesthesia, followed by acquiring fluorescence images during the surgery (pg. 2, 5-ALA in Spinal Tumor Surgery). The 5-ALA is administered orally, which is a form of systemic administration allowing the 5-ALA to travel throughout the body, including allowing it to contact nerves. The acquisition of the fluorescence images involves exposing the nerve to light at least 3 hours after administration of 5-ALA and detecting fluorescence emitted by the nerves being visualized. Therefore, the combined teachings of Pedro and Millesi render claim 3 obvious.
Regarding claims 6 and 7, more specifically regarding the method embodiments of claim 6 depending on the method of claim 3 and the method of claim 7 depending on the method of claim 6, Millesi teaches the oral administration of 5-ALA 3 hours prior to induction of anesthesia, followed by acquiring fluorescence images during the surgery (pg. 2, 5-ALA in Spinal Tumor Surgery). This is an oral systemic means of administration. Therefore, the combined teachings of Pedro and Millesi render claims 6 and 7 obvious.
Regarding claim 8, more specifically regarding the method embodiments of claim 8 depending on the methods of any of claims 1, 3, 6, or 7, Millesi teaches generating the PpIX fluorescence signal by exciting the fluorophore with violet-blue light (pg. 3, Intraoperative PpIX Fluorescence Characteristics of Spinal Tumors, first paragraph). Millesi provides visualization of exposing the nerves to the violet-blue light in Fig. 1 (pg. 4). This method reads on the limitation of exposing a nerve to blue light. Pedro also teaches exposing a peripheral nerve to light to enable fluorescence detection microscope (pg. 2, Study Group, Dosage, and Technical Equipment; and pg. 8, Figure 7). Therefore, the combined teachings of Pedro and Millesi render claim 8 obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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