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 .
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.
Claim 8 is 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 8 recites the limitation "the illuminator" in line 2. There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 1-4 and 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Adey et al. (WO 2018/087155) (Adey) in view of Jenoski et al. (US 2021/0233647) (Jenoski) and Lippert et al. (US 2017/0280076) (Lippert).
Regarding claim 1, Adey discloses an instrument for automatically dissecting a biological specimen on a slide (par [0001], claim 1), wherein the instrument comprises at least one imaging system (par [0058][0059]).
Abey does not specifically disclose that wherein the imaging system comprises at least one camera configured for sequentially imaging at least one image of the slide at a plurality of slide positions,
wherein the instrument comprises a movable xy-stage configured for setting the slide position,
wherein the instrument comprises at least one processing unit configured for generating a full slide image by stitching the sequentially imaged images of the slide.
However, Jenoski discloses wherein the imaging system comprises at least one camera configured for sequentially imaging at least one image of the slide at a plurality of slide positions (par [0162]),
wherein the instrument comprises a movable xy-stage configured for setting the slide position (par [0137] [0138]),
wherein the instrument comprises at least one processing unit configured for generating a full slide image by stitching the sequentially imaged images of the slide (par [0129], [0148] [0164]).
Adey and Jenoski are analogous art because they are from the same field of endeavor and/or contain functional similarities. They both relate to automated imaging and processing of biological specimens mounted on slides. It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection instrument to include Jenoski’s camera-controlled xy-stage scanning and image-stitching arrangement, thereby sequentially imaging the slide and generating a full-slide image. One of ordinary skill in the art would have been motivated to improve complete imaging coverage of the specimen, as suggested by Jenoski, which teaches combining the discrete micro-images “to create a composite image of the entire specimen area 114” (Jenoski par [0129]).
Adey does not specifically disclose wherein the imaging system comprises a relay lens system having a fixed focal length, wherein the relay lens system is configured for relaying an impinging light beam from the slide to the camera,
wherein the relay lens system comprises a plurality of lenses, wherein the lenses are arranged symmetrically or quasi-symmetrically with respect to at least one plane of symmetry perpendicular to an optical axis.
However, Lippert discloses wherein the imaging system comprises a relay lens system having a fixed focal length, wherein the relay lens system is configured for relaying an impinging light beam from the slide to the camera (claim 1),
wherein the relay lens system comprises a plurality of lenses, wherein the lenses are arranged symmetrically or quasi-symmetrically with respect to at least one plane of symmetry perpendicular to an optical axis (claim 6).
Although Lippert does not expressly state that its relay lens system has a fixed focal length, it would have been obvious to configure the relay lens system with a fixed focal length in Jenoski’s scanning arrangement. Jenoski teaches that the slide holder and movement of the xy-stage are aligned in parallel “to provide a constant focal height of the micro images during scanning,” such that the images are acquired at “a single z-axis focal height” (par [0140]). Jenoski separately adjusts focus using Z-stage 200, which controls the position of objective lens 198 (par [0142]). Because movement of the xy-stage changes the lateral x-y position of the slide while maintaining the same z-axis focal height, adjustment of the relay lens system’s focal length would not have been necessary. A fixed-focal-length relay system therefore would have been an obvious and predictable optical setting for scanning successive slide positions.
Adey, Jenoski, and Lippert are analogous art because they are from the same field of endeavor and/or contain functional similarities. They relate to optical imaging of biological specimens using camera-based imaging systems. It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection and whole-slide imaging system to include Lippert’s symmetric multi-lens relay system having a fixed focal length for relaying light from the slide to the camera. One of ordinary skill in the art would have been motivated to improve maintenance of a constant image scale and undistorted imaging across the sequentially imaged slide positions, as suggested by Lippert, which teaches that its symmetric relay provides a 1:1 image scale and that the object plane can be “imaged undistorted onto a detector” (Lippert, claims 1 and 6).
Regarding claim 3, Lippert further teaches that wherein the imaging system has an image scale of about 1:1 (par [0034]).
Regarding claim 4, Lippert teaches wherein the relay lens system comprises a numerical aperture (par [0019]). Although Lippert does not expressly disclose a numerical aperture of 0.05 to 0.5, the numerical aperture was recognized as a result-effective variable affecting the angular range and resolution of the imaging system. It would have been obvious to one of ordinary skill in the art to optimize the numerical aperture within the claimed range according to the desired field of view and resolution because determining a suitable numerical aperture for the intended whole-slide imaging application would have involved no more than routine optical design and experimentation.
Regarding claim 9, Adey teaches wherein the instrument comprises a milling machine for mechanical dissection (par [0073]). Adey’s head assembly and rotating milling tip collectively constitute a milling machine that mechanically dissects selected tissue areas.
Adey further teaches wherein the instrument comprises at least one control unit configured for controlling the milling machine (par [0058] [0059]).
Adey also teaches that the milling operation is controlled based on a slide image (par [0008] [0012]).
Although Adey does not use the specific term “full slide image,” Jenoski provides the full-slide composite image in the claim 1 combination. It would have been obvious to use that full slide image as the slide image on which Adey’s areas of interest are marked because the full slide image provides the image representation of the specimen used to identify and select the tissue regions for dissection. Thus, in the combined system, Adey’s processor controls the milling machine based on annotations or areas of interest identified on Jenoski’s full slide image.
Regarding claim 10, Adey teaches a method for automatically dissecting a biological specimen on a slide using an instrument for automatically dissecting the biological specimen on a slide (par [0001] [0073]).
The instrument recited in claim 10 is taught or suggested by Adey, Jenoski, and Lippert for the reasons set forth regarding claim 1.
Regarding step a), Jenoski teaches setting a plurality of slide positions using the movable xy-stage (par [0146]).
Regarding step b), Jenoski and Lippert teach, at each slide position, relaying an impinging light beam from the slide to the camera by using the relay lens system having a fixed focal length (Lippert, Abstract), and sequentially imaging at least one image of the slide at a plurality of slide positions by using the at least one camera of the at least one imaging system (Jenoski par [0128] [0129] [0146]).
Lippert does not expressly state that its relay lens system has a fixed focal length. However, it would have been obvious to one of ordinary skill in the art to use Lippert’s relay lens system with a fixed focal length in Jenoski’s scanning arrangement. Jenoski teaches that the slide holder and the motion of the xy-stage are aligned in parallel “to provide a constant focal height of the micro images during scanning,” such that the micro-images are acquired at “a single z-axis focal height” (par [0140]). Jenoski separately adjusts focus using Z-stage 200, which controls the position of objective lens 198 (par [0142]). Because the xy-stage moves the slide laterally while maintaining the object at substantially the same focal height, changing the focal length of the relay lens system would not have been necessary. A fixed-focal-length relay lens system therefore would have been an obvious and predictable optical setting for imaging the successive x-y slide positions.
Regarding step c), Jenoski teaches stitching the sequentially imaged images of the slide thereby generating a full slide image by using the processing unit (par [0129][0148][0164]).
Adey and Jenoski are analogous art because they are from the same field of endeavor and/or contain functional similarities. They both relate to automated processing and imaging of biological specimens mounted on slides. It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection method to include Jenoski’s xy-stage scanning and image-stitching process. One of ordinary skill in the art would have been motivated to improve complete imaging coverage of the specimen, as suggested by Jenoski, which combines the discrete micro-images “to create a composite image of the entire specimen area 114” (Jenoski par [0129]).
Adey, Jenoski, and Lippert are analogous art because they relate to optical imaging of biological specimens using camera-based imaging systems. It would have been obvious to one of ordinary skill in the art to perform the above automated tissue-dissection imaging method using Lippert’s symmetric multi-lens relay system having a fixed focal length to relay light from the slide to the camera. One of ordinary skill in the art would have been motivated to improve maintenance of a constant image scale and undistorted imaging across the sequentially imaged slide positions, as suggested by Lippert, which teaches that its symmetric relay produces a 1:1 image scale and permits the object plane to be imaged undistorted onto the detector.
Regarding claim 11, Adey teaches wherein the instrument comprises a milling machine configured for mechanical dissection (par [0073]).
Adey further teaches wherein the method comprises controlling the milling machine based on an image by using a control device of the instrument (par [0058[0059]).
Although Adey does not expressly describe its annotated image as a “full slide image,” Jenoski supplies the full-slide composite image for the reasons set forth regarding claim 10. In the combined method, Adey’s areas of interest would be selected or annotated on Jenoski’s full-slide image, and Adey’s processor-controlled workflow would operate the milling tip to dissect the selected areas. It would have been obvious to use the full-slide image generated in the claim 10 method as the image on which the dissection areas are designated because the full-slide image provides complete image coverage of the specimen for identifying the tissue areas to be mechanically dissected.
Regarding claim 12, Adey teaches wherein the method is computer-implemented (par [0007] [0049]).
Claim 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Adey in view of Jenoski and Lippert, as applied to claim 1, and further in view of Balu et al. (US 2018/0106729) (Balu).
Regarding claim 5, Balu teaches wherein the relay lens system comprises a resolution of less than 20 µm over the full field of view (Abstract: the system “images FOVs of about 0.8 mm² … with lateral and axial resolutions of 0.5 µm and 2.5 µm, respectively”; par [0085]: the instrument “is capable of imaging 0.8×0.8 mm² skin areas at sub-micron resolution”). Balu further teaches that the relay lens system is designed to avoid vignetting and reduction of the field of view and to compensate for optical aberrations introduced by large scanning angles (par [0070]-[0071]).
Regarding claim 6, Balu teaches wherein the camera is a pixelated camera, wherein the camera is a charge-coupled device (CCD) and/or a complimentary metal-oxide semiconductor (CMOS) image sensor (par [0062]).
Adey, Jenoski, Lippert, and Balu are analogous art because they are from the same field of endeavor and/or contain functional similarities. They relate to optical imaging of biological specimens. It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection and whole-slide imaging system to use Balu’s CMOS or CCD camera for imaging the biological specimen. One of ordinary skill in the art would have been motivated to improve rapid visual inspection of the biological specimen, as suggested by Balu (par [0062]).
Regarding claim 7, Balu teaches wherein the instrument comprises at least one illuminator configured for illuminating the slide, wherein the illuminator comprises at least one light source (par [0062]). Balu’s LED or other illumination source 33 constitutes an illuminator comprising a light source and is configured to illuminate the biological sample for imaging by the camera. When incorporated into Adey’s instrument, which images a biological specimen mounted on a slide, Balu’s illumination source would illuminate the claimed slide and its specimen.
It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection and whole-slide imaging system to include Balu’s LED or other illumination source for illuminating the slide-mounted biological specimen. One of ordinary skill in the art would have been motivated to improve quick inspection of the biological specimen, as suggested by Balu (par [0062]).
Regarding claim 8, Balu teaches wherein the instrument comprises at least one transfer element configured for guiding a light beam from the illuminator to the slide and for transmitting light from the relay lens system to the camera. Balu identifies the elements labeled “DM” in Figures 2A and 2B as dichroic mirrors (par [0041]: “FIG. 2A is a schematic of the imaging head implemented in the current microscope, where L denotes a lens or system of lenses; M denotes a mirror; DM denotes a dichroic mirror; and PMT denotes a photomultiplier tube.”). Figure 2A shows the dichroic mirrors in the common optical path between the relay optics/objective and the detectors.
Balu further teaches that the imaging head includes a relay lens system and a microscope objective that scans the tissue with illumination light and returns the resulting optical signal to the detectors (par [0017]: “The imaging head includes: a resonant scanning mirror optically coupled to the pulsed laser; a relay lens system optically coupled to the resonant scanning mirror … and a microscope objective optically coupled to the beam expander, the microscope objective for scanning the tissue and returning a nonlinear optical signal from the tissue to the detectors and data acquisition system.”). Thus, Balu’s dichroic mirror constitutes a transfer element that permits the illumination beam to proceed toward the specimen while separating and directing the returning specimen light toward the detector. In the proposed combination, the specimen is the slide-mounted biological specimen and the detector is the camera of the above whole-slide imaging system.
It would have been obvious to one of ordinary skill in the art to modify the above automated tissue-dissection and whole-slide imaging system to include Balu’s dichroic mirror in the common illumination and imaging path, thereby guiding illumination light toward the slide while permitting the specimen light returning through the relay optics to be directed to the camera. One of ordinary skill in the art would have been motivated to improve compact integration of the illumination and detection optical paths, as suggested by Balu (par [0036]: “the source of pulsed laser light beam, the resonant scanning mirror, the relay lens system, the galvanometer scanning mirror, the beam expander, the high numeric aperture low power microscope objective and the detectors are combined in a single imaging head as a compact integrated optical system”).
Allowable Subject Matter
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The prior art of record, including Adey, Jenoski, and Lippert, does not teach or fairly suggest wherein the relay lens system comprises ten lenses, wherein in direction of propagation of the light beam from the slide to the camera the relay lens comprises a bi-concave lens, a meniscus lens, a bi-convex lens, and a doublet lens, followed by a mirrored symmetric arrangement of said lenses.
Although Lippert teaches a relay system comprising several lenses arranged symmetrically about a plane perpendicular to the optical axis, Lippert does not disclose the claimed number, individual lens types, or their particular sequential and mirrored arrangement.
The remaining prior art of record likewise does not cure this deficiency; for example, Balu teaches a four-achromat 1:1 relay lens system rather than the claimed ten-lens configuration.
Further, the prior art does not provide a reason that would have led one of ordinary skill in the art to select and arrange the particular lens types in the claimed sequence and mirrored configuration. Therefore, the claimed subject matter, considered as a whole, would not have been obvious to one of ordinary skill in the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797
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