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 .
Claims 1, 2, 7, 14-18, 20-23, 31, 34-38, 40, 44, 47, and 48 and pending and currently under consideration.
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.
Claim(s) 1, 2, 7, 14-18, 20, 22, 31, 34, 35, 47, and 48 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xie et al (RSC Adv, 2019, 9: 301-306; 11/7/24 IDS).
Xie et al teaches a compound with the formula B-L-X, where B is folic acid that targets folate receptor, L is a hydrophilic spacer (polyethylene glycol), and X is the NIR-II dye IR-1061 that has an excitation and emission spectra in the second region near infrared (see Scheme 1 on page 302, in particular). Xie et al further teaches a composition comprising said compound and the pharmaceutically acceptable carrier PBS (right column on page 302, in particular). Xie et al further teaches a method of optical or diagnostic imaging of a biological tissue sample that expresses a folate receptor comprising (a) contacting the biological tissue of a subject in vivo with the compound, (b) allowing 4 hours for the compound to distribute within the biological tissue (right column on page 304, in particular), (c) illuminating the biological tissue with an excitation wavelength absorbable by the compound, and (d) detecting an optical signal, that is used to construct an image equivalent to imaging of fluorescence-guided surgery or image-guided surgery, emitted by the compound (see Scheme 2 on page 302, in particular). Xie et al further teaches said method wherein the subject has U87MG brain (glioma; glioblastoma) cancer cells that are contacted with the compound (left column on page 303, in particular) wherein the compound is illuminated at the cancer cells and generating diagnostic imaging (Figs. 4-5, in particular). Said method uses the compound in a multifunctional imaging technique, imaging both PAI and NIR-II (see Scheme 2 on page 302, in particular). As evidenced by https://www.researchgate.net/figure/Absorption-spectrum-of-IR-1061-in-ACN-contributed-by-monomers-dimers-and-interaction_fig5_363246253, it appear the NIR-II dye IR-1061 of Xie et al has an absorption and emission maxima between about 1000 nm and 1700 nm (as recited by instant claim 48).
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, 2, 7, 14-18, 20, 31, 34-38, 40, 47, and 48 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kularatne et al (US 2018/0099934 A1; 4/12/18; 6/30/23 IDS) in view of Tao et al (US 2017/0266323 A1; 9/27/17; 6/30/23 IDS).
Kularatne et al teaches a ”B-X-Y-Z” compound, which is a compound having the formula B-L-X ([0028], in particular), wherein B is a tumor-targeted ligand such as a PSMA-targeted molecule ([0002] and “B” at [0029], in particular), L is hydrophobic linker and an amino acid linker (see “X”, a hydrophobic linker, and “Y”, an amino acid linker, at [0030]-[0031] and [0034], in particular), and X is an NIR dye (see “Z” at [0032], in particular). Kularatne et al further teaches the compound is to be used in image-guided surgery, targeted imaging of tumors (including prostate cancer tumors) expressing PSMA, treating diseases, and diagnosing diseases with pathological populations of cells expressing PSMA ([0027] and [0062], in particular). Kularatne et al further teaches administering to a subject a composition comprising said compound and a pharmaceutically acceptable carrier, excipient or diluent ([0060], in particular). Kularatne et al further teaches a method of optical or diagnostic imaging of a biological tissue that expresses PSMA comprising (a) contacting the biological tissue of a subject with the compound, (b) allowing time for the compound to distribute within the biological sample, (c) illuminating the biological tissue with an excitation wavelength absorbable by the compound, and (d) detecting an optical signal emitted by the compound ([0172]-[0176], in particular). Kularatne et al further teaches said method wherein an image is constructed from the detected signal to detect diseases associated with high PSMA expression ([0177], in particular). Kularatne et al further teaches said method performed in vivo in mice where the mice were euthanized two hours after administering the compound prior to imaging ([0245] and Fig. 3, in particular). Kularatne et al further teaches said method wherein a second compound with a distinguishingly different signal is administered ([0177], in particular). Kularatne et al further teaches said method wherein the illuminating and/or detecting steps are performed with a device such as an endoscope or hand-held optical imaging system ([0177], in particular).
Kularatne et al does not specifically teach an NIR-II dye. However, these deficiencies are made up in the teachings of Tao et al.
Tao et al teaches NIR-II dyes, including IR-1061, for imaging in order to reduce optical absorption and lower autofluorescence as compared to NIR dyes (FIG. 1.1 and [0002], in particular). Tao et al further teaches NIR-II dyes are detected in the second near-infrared range of 1000-1700 nm, which is different than the traditional 700-800 NIR region ([0066], in particular). Tao et al further illustrates absorption and emission spectra with NIR-II emission at 1047 nm (FIG 2.1(c)). Tao et al further teaches detecting NIR-II dyes in vivo using epifluorescence microscopic imaging or two-photon fluorescence microscope ([0295], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of diagnostic imaging of PSMA-expressing prostate cancer tissue for image-guided surgery comprising performing the method of Kularatne et al comprising: (a) contacting, in vivo, a biological tissue of a subject that is abnormal tissue suspected to be prostate cancer tumor with the ”B-X-Y-Z” compound of Kularatne et al wherein the NIR dye of the compound is an NIR-II dye of Tao et al (such as IR-1061); (b) allowing time for the compound to distribute within the biological tissue for any period of time less than 2 hours (a period of time after contacting Kularatne et al has demonstrated able to detect dye in vivo); (c) illuminating the biological tissue with an excitation wavelength absorbable by the NIR-II taught by Tao et al; and (d) detecting an optical signal emitted by the compound with any device capable of detecting the signal, including an epifluorescence microscopic imaging or two-photon fluorescence microscope of Tao et al, to construct an image that diagnoses the subject as having PSMA-expressing prostate cancer tissue and because the method of Kularatne et al is a method of diagnostic imaging of PSMA-expressing prostate cancer tissue for image-guided surgery using an NIR dye and Tao et al teaches Tao et al teaches NIR-II dyes, including IR-1061, for imaging in order to reduce optical absorption and lower autofluorescence as compared to NIR dyes (FIG. 1.1 and [0002], in particular). One would be motivated to substitute the NIR-II dye of Tao et al in place of the NIR dye of Kularatne et al because Tao et al teaches NIR-II dyes, including IR-1061, have the benefit of reduced optical absorption and lower autofluorescence as compared to NIR dyes. This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 7, 14-18, 20, 22, 23, 31, 34-38, 40, 44, 47, and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kularatne et al (US 2018/0099934 A1; 4/12/18; 6/30/23 IDS) in view of Tao et al (US 2017/0266323 A1; 9/21/17; 6/30/23 IDS) as applied to claims 1, 2, 7, 14-18, 20, 31, 34-38, 40, 47, and 48 above, and further in view of Diamond et al (Frontiers in Oncology, 2012, 2(Article 131): 1-11) and Ried et al (Asian Pacific Journal of Cancer Prevention, 2017, 18(8): 2275-2285).
Teachings of Kularatne et al and Tao et al are discussed above.
Kularatne et al and Tao et al do not specifically teach detecting PSMA-expression circulating tumor cells (CTCs) or enriching CTCs. However, these deficiencies are made up in the teachings of Diamond et al and Ried et al.
Diamond et al teaches PSMA is detected on prostate cancer circulating tumor cells (CTCs) (right column on page 3, in particular). Diamond et al further teaches CTCs can be enriched from a subject by means such as size-dependent selection (left column on page 5, in particular).
Ried et al teaches CTC screening provides a highly sensitive biomarker for early detection of cancer, with higher counts being associated with higher risk of malignancy, and that CTC monitoring over time indicates treatment effectiveness (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Kularatne et al and Tao et al wherein (i) the patient is a patient suspected of having prostate cancer or a patient that has been treated for prostate cancer and (ii) the sample is a sample of CTCs enriched by size-dependent selection, as opposed to an abnormal tissue suspected to be prostate cancer tumor, in an effort to determine whether the patient has prostate cancer or to monitor the patient post-treatment to determine whether the patient therapeutically benefited from prostate cancer treatment because Diamond et al teaches PSMA is detected on prostate cancer CTCs and Ried et al teaches CTC screening provides a highly sensitive biomarker for early detection of cancer, with higher counts being associated with higher risk of malignancy, and that CTC monitoring over time indicates treatment effectiveness (Abstract, in particular). Such monitoring is “real-time monitoring, screening, and management of a subject having a disease,” as recited by instant claim 23. Regarding instant claim 22, the combined method is a “multifunctional imaging technique” because the combined method provides the function of early detection of cancer, provides the function of determining treatment effectiveness, and provides imaging of PSMA+ CTCs.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 7, 14-18, 20, 21, 31, 34-38, 40, 47, and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kularatne et al (US 2018/0099934 A1; 4/12/18; 6/30/23 IDS) in view of Tao et al (US 2017/0266323 A1; 9/21/17; 6/30/23 IDS) as applied to claims 1, 2, 7, 14-18, 20, 31, 34-38, 40, 47, and 48 above, and further in view of Lu et al (Nature Communications, 2020, 11(4192): 1-11).
Teachings of Kularatne et al and Tao et al are discussed above.
Kularatne et al and Tao et al do not specifically teach a method that employs bioluminescence resonance energy transfer (BRET) or two-step fluorescence resonance energy transfer (FRET). However, these deficiencies are made up in the teachings of Lu et al.
Lu et al teaches “the necessity of external illuminations for excitation in in vivo NIR-II fluorescence imaging inevitably leads to other unfavorable outcomes, such as auto-fluorescence background, potential light-induced overheating effect and in homogenous illumination in a wide-field imaging” (left column on page 2, in particular). Lu et al further teaches such challenges can be overcome by employing a BRET process with a two-step FRET process using the NIR-II FD-1029 (paragraph spanning column on page 2 and Figure 1, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Kularatne et al and Tao et al wherein the NIR-II of the compound is FD-1029 and the method employs a BRET process with a two-step FRET process using the NIR-II FD-1029 without providing external illuminations in an effort to overcome unfavorable outcomes from external illuminations because the combined method of Kularatne et al and Tao et al provided illuminations using a device (such as an endoscope) for excitation of NIR-II and Lu et al teaches “the necessity of external illuminations for excitation in in vivo NIR-II fluorescence imaging inevitably leads to other unfavorable outcomes, such as auto-fluorescence background, potential light-induced overheating effect and in homogenous illumination in a wide-field imaging” (left column on page 2, in particular) and that such challenges can be overcome by employing a BRET process with a two-step FRET process using the NIR-II FD-1029 (paragraph spanning column on page 2 and Figure 1, in particular). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642