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 § 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.
Claim(s) 30, 37, 40-41, 44, 49-51 and 53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Trulson et al. (US Pub No. 2018/0303573) in view Cantin et al. (US Pub No. 2006/0129210).
With regards to claim 30, Trulson et al. disclose a portable system for combined modulation and imaging of cellular activity in vivo (paragraphs [0073]-[0074], referring to the microscope/optical assembly being coupled with a probe that can deliver imaging light and stimulation light to a subject in vivo), the portable system comprising:
a) a laser (108 or 708/709) (paragraphs [0061]-[0062], referring to the stimulation light source which can comprise of light sources such as “laser diodes” or “vertical-cavity surface-emitting lasers (VCSEL)”; Figures 1 and 7);
b) a collimation lens (110 or 112)) (paragraph [0064], referring to the condenser lens (110) which can collimate the stimulation light; paragraph [0065], referring to the second condenser lens (112) which can collect light from the stimulation light source and/or the imaging light source and redirect this light into a collimated beam for delivery to the sample Figures 1, 7);
c) a spatial light modulator (SLM) (paragraphs [0005], [0007], [0009], referring to the stimulation light source comprising a single stimulation light source that is patterned by a spatial light modulator);
d) a light source (103 or 708/709) (paragraph [0010], referring to the optical assembly including an imaging light source comprising one or more light-emitting elements; paragraphs [0051], [0058]-[0059], referring to the imaging light source which may comprise one or more LEDs and can further be an excitation light source such that when light from the imaging light is incident on the sample, the sample emits fluorescence from one or more fluorophores contained in the sample; paragraph [0108], referring to the imaging light being provided by light sources (708/709); Figures 1, 7);
e) an excitation dichroic mirror (136 or 707) (paragraphs [0064]-[0065], referring to the stimulation light and the imaging light being directed through a dichroic mirror (136); paragraph [0108], referring to the dichroic mirror (707); Figures 1, 7);
f) an excitation lens (110 or 112; 706) (paragraph [0064], referring to the condenser lens (110) which can collimate the stimulation light; paragraph [0065], referring to the second condenser lens (112) which can collect light from the stimulation light source and/or the imaging light source; paragraph [0108], referring to the lens (706); Figures 1, 7);
g) a main dichroic mirror (134, 704) (paragraph [0066], referring to the second dichroic element (134); paragraph [0108], referring to the dichroic mirror (704); Figures 1, 7),
h) an implanted lens (701 and/or 702) configured for placement in a tissue of the subject (paragraph [0109], referring to the GRIN lens (701) and optional corrective optical element (702) comprising the “objective” lens of the system and are components of an endoscopic probe that is designed to be inserted into (e.g., partially implanted in) the subject; paragraph [0135], referring to the compact optogenetic microscope being implanted within the subject; Figures 1, 7); and
i) an image sensor (126 or 712) (paragraph [0067], referring to light from the sample being directed through an optical path to an image sensor (126) to generate a digital representation of the image of the sample; paragraph [0108], referring to the image sensor (712); Figures 1, 7),
wherein
( i) laser beams from the laser (102; 708 or 709) refract through the collimation lens (110) to generate collimated laser beams, wherein the laser light is reflected by the spatial light modulator to generate a patterned excitation light path (108) which is reflected by the main dichroic mirror (134) onto the implanted lens (i.e. GRIN lens), thereby transferring the patterned excitation light path to a stimulation area on the tissue of the subject and inducing patterned modulation of cellular activity within the stimulation area (paragraphs [0051], [0064]-[0068]; [0108]-[0111]; Figures 1 and 7), ( ii) light rays from the light source (103) are reflected by the excitation dichroic mirror (136) onto the excitation lens (112), refract through the excitation lens onto the main dichroic mirror (134), and are subsequently reflected by the main dichroic mirror onto the implanted lens (i.e. GRIN lens), thereby transferring light energy from the single photon light source to an illumination area on the tissue of the subject (paragraphs [0051], [0064]-[0068]; [0108]-[0111]; paragraph [0010]).
(iii) overlap between the illumination area and the stimulation area within the tissue is at least 90% (paragraphs [0010], [0096]-[0097], referring to the stimulation light may “fully” overlap with the imaging light, which would encompass at least 90% overlap between the illumination area and the stimulation area; Figure 2).
However, though Trulson et al. do disclose that the laser light is reflected by the spatial light modulator, the above combined references do not specifically disclose that it is specifically the collimated laser beams that are reflected by the spatial light modulator.
Cantin et al. disclose a device and method for transmitting multiple optically-encoded stimulation signals to multiple stimulation sites, especially cell locations (Abstract). Light sources (30) emit a collimated light beam (32), wherein a spatial modulator may be positioned downstream each source to ultimately provide target, pre-modulated wavelength components from each source light beam (32) (paragraph [0064]; Figure 5).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have the spatial modulator of the above combined references be positioned downstream of the collimated laser beams, and thus have the collimated laser beams of the above combined references be reflected by the spatial light modulator, as taught by Cantin et al., in order to effectively provide target, pre-modulated wavelength components from each source light beam (paragraph [0064]) and/or to provide the spatial modulator in a known, effective position to provide a modulated collimated laser beam.
With regards to claim 37, Trulson et al. disclose that the illumination area and the stimulation area are each circular areas having an average diameter of at least 150 microns (paragraph [0010], referring to the imaging source directing imaging light to tissue within a specified field-of-view, wherein the stimulation light source is configured to direct stimulation light to tissue within at least a portion of said field-of-view; paragraphs [0096], [0101], referring to the field-of-view (204 or 301/303) which are depicted in Figures 2B and 3 as substantially circular areas; paragraph [0084], referring to the field-of-view being at least about 0.2 mm^2, 0.3. mm^2, 0.4 mm^2, etc., which would provide a diameter of at least 150 microns; Figures 2B, 3).
With regards to claim 40, Trulson et al. disclose that the light energy transferred from the light source to the tissue of the subject illuminates a detectable signal from a calcium indicator present in the tissue of the subject, and wherein an image of the detectable signal is generated by the image sensor (paragraphs [0138], [0150], [0157]-[0158], referring to application of the implantable microscope systems including optical stimulation of genetically-modified tissue in a subject, wherein the tissue has been genetically modified to incorporate fluorescent calcium indicators and calcium imaging; paragraphs [0004], [0149], referring to images being generated by the imaging light; Figure 8B).
With regards to claim 41, Trulson et al. disclose that the system further comprises an excitation filter (114) operably connected to the light source to select for light of a first wavelength (paragraphs [0065], [0152]-[0153], referring to the excitation filter (114); Figures 1, 7).
With regards to claim 44, Trulson et al. disclose that the image sensor is a complementary metal oxide semiconductor (CMOS) image sensor, wherein the implanted lens is a gradient index (GRIN) lens (701), wherein the excitation lens is an achromatic lens, and/or wherein the portable system weighs 8g or less (paragraph [0115], referring to the image sensor including CMOS image sensors; paragraph [0108], referring to the GRIN lens (701); paragraph [0011], referring to the total weight of the system being less than 4 grams, and thus less than 8 grams; Figures 1, 7).
With regards to claim 49, Trulson et al. disclose a method for combined manipulation and imaging of cellular activity in vivo, the method comprising:
a. connecting the portable system of claim 30 [see above rejection of claim 30] to a tissue of the subject (paragraph [0020], referring to the method comprising providing the optical system and mounting or implanting the optical step on or within the subject);
b. generating laser beams from the laser, thereby transferring a patterned excitation light path to a stimulation area on the tissue and inducing a patterned manipulation of cellular activity for one or more cells within the stimulation area (paragraph [0020], referring to the method further comprising directing stimulation light to the tissue of said subject in a spatially-modulated manner; paragraph [0005], referring to the stimulation light source including a stimulation light source that is patterned by a spatial light modulator, wherein the patterned stimulation light is spatially modulated; paragraphs [0057], [0086], [0089], [0150], referring to observing the cellular activity patterns that occur between a first group of cells and a second group of cells when at least one of the groups of cells is stimulated);
c. generating light rays from the light source, thereby illuminating a detectable signal from an indicator present in the tissue of the subject (paragraph [0010], referring to the optical assembly including an imaging light source comprising one or more light-emitting elements; paragraphs [0051], [0058]-[0059], referring to the imaging light source which may comprise one or more LEDs and can further be an excitation light source such that when light from the imaging light is incident on the sample, the sample emits fluorescence from one or more fluorophores contained in the sample; paragraph [0108], referring to the imaging light being provided by light sources (708/709); Figures 1, 7); and
d. obtaining an image of the detectable signal (paragraph [0067], referring to light from the sample being directed through an optical path to an image sensor (126) to generate a digital representation of the image of the sample).
With regards to claim 50, Trulson et al. disclose that the method further comprises converting the image of the detectable signal to a readout of a cellular activity pattern of the one or more cells in the subject (paragraphs [0089], [0150], referring to the user observing activity using the imaging light from the system, wherein when the user observes the activity the user can provide stimulation light to at least a portion of the sample to inhibit the activity, etc.; Figures 9-13).
With regards to claim 51, Trulson et al. disclose that the method further comprises mimicking the cellular activity pattern of the one or more cells, wherein mimicking the cellular activity pattern of the one or more cells comprises selectively targeting the one or more cells with the patterned excitation light path, such that a patterned modulation of activity for the one or more cells is induced (paragraph [0100], referring to generating patterned stimulation, wherein an algorithm can determine which stimulation light sources in an array/matrix of light sources should be illuminated in order to direct stimulation light to the one or more objects of interest detected in the image; paragraph [0020], referring to the method further comprising directing stimulation light to the tissue of said subject in a spatially-modulated manner; paragraph [0005], referring to the stimulation light source including a stimulation light source that is patterned by a spatial light modulator, wherein the patterned stimulation light is spatially modulated; paragraphs [0057], [0086], [0089], [0150], referring to observing the cellular activity patterns that occur between a first group of cells and a second group of cells when at least one of the groups of cells is stimulated; paragraph [0102], referring to the user detecting a population of neurons in the image of the sample and choosing a stimulation light pattern to provide stimulation light to the population of neurons).
With regards to claim 53, Trulson et al. disclose that the indicator is a calcium indicator and/or wherein the one or more cells comprise neurons (paragraphs [0138], [0150], [0157]-[0158], referring to application of the implantable microscope systems including optical stimulation of genetically-modified tissue in a subject, wherein the tissue has been genetically modified to incorporate fluorescent calcium indicators and calcium imaging; paragraph [0102], referring to the user detecting a population of neurons in the image of the sample and choosing a stimulation light pattern to provide stimulation light to the population of neurons).
Claim(s) 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Trulson et al. in view of Cantin et al., as applied to claim 30 above, and further in view of Lee et al. (US Pub No. 2019/0059737).
With regards to claim 31, as discussed above, the above combined references meet the limitations of claim 30.
However, though Trulson et al. do disclose that their system comprises an imaging light source [which may also serve as an excitation light source] (paragraphs [0013], [0051], [0058]-[0059], referring to the imaging light source which may comprise one or more LEDs and can further be an excitation light source such that when light from the imaging light is incident on the sample, the sample emits fluorescence from one or more fluorophores contained in the sample), the above combined references do not specifically disclose that the light source is specifically a “single photon” light source.
Lee et al. disclose an imaging device, wherein biological tissue is subjected to fluorescent image-capture through single-photon excitation with visible wavelength light, thereby obtaining morphological information of cells in the biological tissue at a high speed without damage (Abstract; paragraphs [0023], [0080], [0086]).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have the light source of the above combined references comprise a single photon light source, as taught by Lee et al., in order to obtain morphological information of cells in the biological tissue at a high speed without damage (Abstract; paragraphs [0023]).
Response to Arguments
Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive.
With regards to claim 30, Applicant argues that Trulson does not disclose a system wherein collimated laser beams are reflected by a spatial light modulator to generate a patterned excitation light path that induces patterned modulation of cellular activation and Cantin also does not disclose or suggest a device comprising a spatial light modulator that reflects collimated laser beams to generate a patterned excitation light path on a tissue. With regards to Cantin, Applicant argues that the spatial light modulator of Cantin serves an entirely different purpose, specifically severing to receive different wavelengths of light and direct them to an optical fiber to form a multiplexed signal and is not used to reflect a collimated laser beam and generate a patterned excitation light path for patterned modulation of cellular activity.
Examiner respectfully disagrees and notes that claim 30 is rejected under the combination of Trulson in view of Cantin, wherein Trulson is relied upon to teach that light/laser beams are reflected by a spatial light modulator to generate a patterned excitation light path (108) (see Figures 1 and 7, further see cited paragraphs [0005], [0007] and [0009] of Trulson for the spatial light modulator, which sets forth that the stimulation light source comprises a single stimulation light source that is patterned by a spatial light modulator; note further that paragraph [0094] of Trulson sets forth that the light sources can be directed through a spatial light modulator and light sources can include light patterned through a coupled fiber bundle). However, though Trulson does disclose that light is reflected by the spatial light modulator to generate a patterned excitation light, Trulson do not specifically disclose that it is the “collimated laser beams” that are reflected by the spatial light modulator. Examiner emphasizes that Trulson does disclose light/laser beams being reflected by the spatial light modulator as claimed, but does not specifically set forth that the collimation of the light/laser beams occurs prior to the light/laser beams being reflected by the spatial light modulator, and therefore it is not clear that the light/laser beams of Trulson that are reflected by the spatial light modulator are specifically the “collimated” laser beams. Cantin is solely relied upon to teach that a spatial modulator may be positioned downstream each source that emits a collimated beam (32). Trulson is modified in view of this teaching of Cantin in order to provide the spatial modulator in a known, effective position to provide a modulated collimated laser beam, etc., thus providing the collimated laser beams of Trulson to be reflected by the spatial light modulator [which, as taught by Cantin, is positioned downstream of the collimated laser beams]. Examiner emphasizes that the above rejection does not rely on the Cantin reference to teach the spatial modulator, but rather, Cantin is soley relied upon to teach the placement of the spatial modulator with respect to the collimated laser beams.
The claims therefore remain rejected under the previously applied prior art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kurtz (US Pub No. 2007/0021807) discloses a medical device for optically stimulating the formation of collagen in tissue, wherein a collimated input light beam is presented to a spatial light modulator (340) (paragraph [0050]).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/KATHERINE L FERNANDEZ/Primary Examiner, Art Unit 3798