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 .
Specification
The disclosure is objected to because of the following informalities:
In paragraph [0194], reference is made to Figure 1, but the drawings show Figures 1A-1D.
In the detailed description, there is no description or reference to Figures 11 and 13-16.
Appropriate correction is required.
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 90-103 are rejected under 35 U.S.C. 103 as being unpatentable over Hama (“Two-Color Lymphatic Mapping Using Ig-Conjugated Near Infrared Optical Probes” –cited by applicant) in view of Bradbury et al (Bradbury-NPL) (“Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions” -cited by applicant).
Re claims 90, 98, 99: Hama discloses a method comprising:
administering two or more different probe species each comprising a spectrally differentiable fluorescent reporter to a lymphatic system of a subject with a tumor, wherein a first probe species is administered to a tumor site in a trunk and a second probe species is administered to an extremity of the subject (pg 2352; see the interstitial injections into lymph ducts of Cy5.5 into the breast (which is part of the trunk/torso of a subject) and Cy7 into the upper extremity for NIR spectral resolved lymphangiography, and (pg 2353 column 1) wherein the subject has melanoma or other malignancy, thereby indicating that the probe species is administered to a tumor site);
directing excitation light into the lymph nodes of the subject, thereby exciting the fluorescent reporters having spectrally distinguishable emission wavelengths (pg 2355; see “Fluorescence microscopy” portion citing the different wavelengths of the probes);
identifying a lymph node in the trunk for harvesting in transplantation that drains the tumor site, and identifying another lymph note that drains the extremity, using a fluorescence camera system that detects the wavelengths (Abstract, pg 2354; see the mapping of lymph nodes that could guide lymphadenectomy; pg 2355; see the Maestro in-vivo imaging system, which is uses detection with a CCD camera);
displaying the reporters to graphically differentiate the lymph node that drains the extremity and the node that drains the tumor site (pg 2355, 2nd column, 3rd full paragraph; see the imaging system to display the image showing the two nodes or drain pathways; Figures 3 and 4 showing the two kinds of nodes and drainage pathways).
Hama discloses all features including use of nanoparticles as IG-conjugated particles for lymph node mapping, but does not disclose that the probe species each comprise a silica nanoparticle with a diameter less than 10 nm. Hama also does not disclose that the particular Maestro camera system simultaneously detects the wavelengths in real-time or that it is handheld or that the subject is a human. However, Bradbury-NPL teaches of a procedure for lymph node mapping wherein silica nanoparticles with dye-rich cores are utilized (pg 75 column 2; see the I-cRGDY-PEG-C dots with silica shells and core-containing reactive dye molecules), wherein the nanoparticles have diameters less than 10 nm (pg 77 column 1, line 1). Further, the injection of the dots is administered to the tumor site in a human (see abstract with reference to clinically-translated for human subjects and pg 80 column 1; see the injection of the dots about the tumor site) and wherein the handheld multi-channel ArteMIS fluorescence camera system is used for simultaneous multichannel detection in real time (pg 79; pg 84; first full paragraph, see the ArteMIS handheld real-time camera). It would have been obvious to the skilled artisan to modify Hama, to utilize the silica nanoparticles and the ArteMIS camera as taught by Bradbury-NPL, as such are well-known nanoparticles used for lymph node mapping and would be applied via simple substitution of the nanoparticle and also because the silica nanoparticle would provide for improved detection and localization of lymph node metastases (pg 76 column 1, pg 77 column 1; see the drawbacks of traditional Cy7 and Cy5.5 dyes and see the improve detection when using silica nanoparticles). Further, the ArteMIS camera would permit a more efficient procedure as it would not be necessary to rely on a filter that is stepped in 10 nm increments (as is done with the Maestro camera of Hama).
Re claims 91, 97: Hama discloses the tumor site comprises a member selected from the group consisting of a breast, a trunk, an abdomen, a pelvis, and a thoracic cavity (pg 2352; see the breast).
Re claims 92, 100: Hama discloses the extremity comprises a member selected from the group consisting of an upper limb and a lower limb (pg 2352; see the upper extremity).
Re claims 93, 101: Hama discloses the method includes detecting fluorescent light of spectrally different emission wavelengths, the detected fluorescent light having been emitted by the fluorescent reporters of the respective probe species in the lymph nodes and/or drainage pathways as a result of illumination by excitation light so as to discriminate between signals received from each probe species (Abstract; see the separate and simultaneous visualization of the drainage patterns from the lymph vessels; pg 2355; see the different wavelengths). Hama also does not disclose simultaneously detection. However, Bradbury-NPL teaches that the multi-channel ArteMIS fluorescence camera system is used and this permits simultaneous multichannel detection in real time (pg 8; first full paragraph). It would have been obvious to the skilled artisan to modify Hama, to utilize the ArteMIS camera as taught by Bradbury-NPL, as the ArteMIS camera would permit a more efficient procedure as it would not be necessary to rely on a filter that is stepped in 10 nm increments (as is done with the Maestro camera of Hama).
Re claims 94, 102: Hama discloses the fluorescent reporter of a first probe species having received the excitation light fluoresces at a spectrally distinguishable wavelength compared to a second fluorescent reporter of another probe species having received the excitation light (pg 2355; see “Fluorescence microscopy” with the different wavelengths for the two reporters).
Re claim 95: Hama discloses the method further comprising identifying an appropriate lymph node for excision (Abstract, pg 2354; see the lymph node resection and see mapping of lymph nodes that could guide lymphadenectomy).
Re claims 96, 103: Hama discloses the method includes displaying a map of lymph nodes and/or lymphatic pathways of the lymphatic system, wherein the map graphically differentiates between specific lymph nodes and/or between specific lymph node types (Figures 3, 4: see the Cy5.5 and Cy7 images showing the different lymph nodes and node types, as well as drainage pathways).
Response to Arguments
Applicant's arguments filed 9/27/23 have been fully considered but they are not persuasive. Applicant has amended independent claim1 and added new independent claim 91 and argues that Hama/Bradbury-NPL does not meet the limitations. Respectfully, the Examiner disagrees.
Applicant first argues that because Hama’s conjugated dyes already overcome the drawbacks of traditional dyes, there would be no reason to instead use Bradbury-NPL’s silica nanoparticles. However, the Examiner maintains that the modification of Hama to use Bradbury-NPL’s nanoparticles would be applied via simple substitution also because the silica nanoparticle would provide for improved detection and localization of lymph node metastases (pg 76 column 1, pg 77 column 1; see the drawbacks of traditional Cy7 and Cy5.5 dyes and see the improve detection when using silica nanoparticles). Applicant has not addressed the 103 rationale of simple substitution. Regarding the rationale of “improved detection and localization”, Applicant asserts that Hama’s probes are conjugated and thus already overcome drawbacks of traditional dyes. However, Bradbury-NPL’s discussion of drawbacks of traditional dyes does not indicate that the combination wouldn’t be made by the skilled artisan. In other words, that the probes of Hama and Bradbury-NPL both may overcome the drawbacks of traditional dyes does not preclude the skilled artisan from utilizing the silica nanoparticles instead of the conjugated probes of Hama. For example, the use of silica nanoparticles permits multiple functions to be combined into a single vehicle which allows for the “improved detection and localization”. Further, the modification results in silica nanoparticles as the probes and they have less than 10 nm diameters as claimed.
Regarding the camera for simultaneous detection met by replacing the imager of Hama with the imager of Bradbury-NPL, Applicant argues that such amounts to hindsight. However, the Examiner finds that the rationale to use the imager in Bradbury-NPL is that the ArteMIS camera would permit a more efficient procedure as it would not be necessary to rely on a filter that is stepped in 10 nm increments (as is done with the Maestro camera of Hama). Hama’s goal is to simultaneously visualize draining patterns from the probe species (see Figure 1 with an image showing Cy5.5 and Cy7 reporters) but is limited by the use of a filter that is stepped in 10 nm increments (thereby not allowing actual simultaneous detection). Bradbury-NPL’s ArteMIS camera allows for the actual simultaneous detection for efficiency. Both Hama’s Maestro and Bradbury-NPL’s ArteMIS systems are fluorescence imaging system and the skilled artisan would be motivated to use the ArteMIS imager for the benefit of simultaneous imaging. Contrary to Applicant assertions, this modification does not amount to hindsight.
Regarding Hama’s discussion of preclinical work, Applicant has amended the claim 1 to recite a “human” subject. However, the Examiner maintains his position. In Hamas, the mapping in normal mice (preclinically) is used to show the ability of the system to visualize drainage patterns from two separate lymphatic vessels while the actual usage is said to be for cancer detection. Hama provides an enabling disclosure for clinical use because the application to clinical use is clear and enables the person of ordinary skill to carry out the clinical procedure. Hama does state that that further work is required before clinical application is possible. However, the Examiner reads this portion as ‘further work is required to optimize these probes for clinical application’. The ‘further work’ is said to be needed to optimize probes (i.e. of an optimal wavelength) and does not indicate that the method cannot be performed clinically. Even if it were the case that the method could only be performed preclinically, Bradbury-NPL provides for “clinically-translated silica nanoparticles”. The Examiner finds that the ability of the system for “preoperative mapping of lymph nodes before lymph node resection” for diagnosing/treating cancer appears to be the goal/purpose of developing the mapping system and visualizing drainage patterns. The testing of mice is used to demonstrate how the mapping is able to distinguish drainage patterns and the mere testing of normal mice is clearly not why the mapping system was developed. Therefore, the application of the mapping system for cancer detection is not just a potential future clinical application. Hama discloses applying the method to mice without tumors, but the disclosure as a whole relays that the method is to be applied to a human subject with tumors. Furthermore, there would be a reasonable expectation of success.
In addition, the 112b rejection is withdrawn.
Conclusion
This is a CON of applicant's earlier Application No. 16/060,463. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the earlier application. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL T ROZANSKI whose telephone number is (571)272-1648. The examiner can normally be reached Mon - Fri 8:00-4:00.
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/MICHAEL T ROZANSKI/Primary Examiner, Art Unit 3797