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
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.
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.
Claim(s) 1-3, 6-17, 19-22, 24-25, 27-31, and 35-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang (US 2017/0138860) in view of Krishnan et al. (US 2008/0213215; hereinafter Krishnan), Gambhir (US 2010/0166650; hereinafter Gambhir), and Bechtel et al. (US 2012/0203114; hereinafter Bechtel).
Huang shows a method and apparatus for measuring, in vivo, water content in a sub-surface tissue of a human or animal subject, through diffusely scattering overlying tissue ([0081]), comprising: directing probe light to an entry region on a surface of the overlying tissue ([0083]-[0084]); collecting said probe light from a collection region on the surface of the overlying tissue, the collection region being spatially offset from the entry region, the collected probe light comprising probe light inelastically scattered into the Raman OH stretching bands by water present in the sub-surface tissue (water stretching bands, [0102]; it is noted that light enters the tissue and penetrates to some depth beneath the surface of the tissue, such that the optical type measurements include a collection region spatially offset from an entry region, Figure 1); detecting, in the collected probe light, one or more first spectral features of the probe light inelastically scattered into the Raman OH stretching bands ([0102], [0141], [0173], [0179], [0202]); and measuring water content in the sub-surface tissue using the one or more first spectral features ([0151]-[0153]).
Huang also shows wherein the Raman OH stretching bands extend at least from a wavenumber shift of about 2800 cm-1 to a wavenumber shift of about 3700 cm-1 ([0099]-[0102], [0111]); wherein the Raman OH stretching bands comprise a first spectral peak at about 3400 cm-1 ([0102], and the one or more first spectral features comprise one or more of: an area under at least a portion of the first spectral peak, and a magnitude of at least a portion of the first spectral peak ([0123]); the collected probe light further comprises probe light inelastically scattered into the Raman CH stretching bands by C-H bonds present in the sub-surface tissue ([0099]-[0101], [0136]-[0140]); the method comprises detecting, in the collected probe light, one or more second spectral features of probe light inelastically scattered into the Raman spectral CH stretching bands ([0099]-[0101], [0136]-[0140]); and water content of the sub-surface tissue is measured using the one or more first spectral features and the one or more second spectral features ([0153]); wherein the Raman CH stretching bands extend at least from a wavenumber shift of about 2800 cm-1 to a wavenumber shift of about 3100 cm-1 ([0099]-[0101], [0136]-[0140]); wherein the Raman CH stretching bands provide a second spectral peak at about 2900 cm-1 ([0099]-[0101], [0136]-[0140], [0144]), and the one or more second spectral features comprise one or more of: an area under at least a portion of the second spectral peak; and a magnitude of at least a portion of the second spectral peak ([0123]); wherein: the probe light further comprises probe light inelastically scattered into the Raman fingerprint region by one or more chemical components of the sub-surface tissue ([0090]-[0098], [0111], [0153]); the method comprises detecting, in the collected probe light, one or more third spectral features of probe light inelastically scattered into the Raman fingerprint region ([0090]-[0098], [0111], [0153]); and measuring the chemical components of the sub-surface tissue using the one or more third spectral features ([0090]-[0098], [0111], [0153]); wherein the Raman fingerprint region extends up to a wavenumber shift of about 1800 cm-1 ([0111]); further comprising determining an indication of the sub-surface tissue being cancerous from the measured water content ([0111], [0152], [0178]); wherein the determining an indication of the sub- surface tissue being cancerous also uses one or more spectral features detected in the collected probe light of the Raman fingerprint region ([0111], [0152]-[0153], [0178]); wherein the one or more spectral features detected in the collected probe light of the Raman fingerprint region are indicative of one or more of: characteristic changes within nucleic and/or amino acids associated with dysfunctional tissues; lesion related calcifications; protein to lipid ratios associated with dysfunctional tissues; and protein conformations associated with dysfunctional tissues ([0081], [0153]); wherein measuring water content of the sub-surface tissue comprises determining an elevated water content of the sub-surface tissue ([0151]); further comprising generating a map of one or more of: measured water content in the sub-surface tissue; and an indication of the sub-surface tissue being cancerous, wherein the map corresponds to the plane of the surface ([0282]); wherein the map is generated from repeated measurements of water content or repeated indications of the sub-surface tissue being cancerous, taken at different positions across the surface ([0282]); wherein the sub-surface tissue is a subcutaneous tissue of the human or animal subject, and the diffusely scattering overlying tissue comprises skin of the subject ([0240], [0251], [0266], [0287]).
While Huang shows the spectra are normalized over the integrated area under the FP and HW ranges, where the HW range encompasses the C—H stretch band ([0221]), Huang fails to explicitly state measuring water content in the sub-surface tissue using the one or more first spectral features normalized using the one or more second spectral features.
Huang furthermore teaches that the invention is not limited to endoscope type embodiments and may be utilized for external measurements through the skin of the patient ([0251], [0266]). Huang fails to explicitly show carrying out repeated measurements through the skin, of water content in the sub-cutaneous tissue, at least 2 mm beneath the surface of the skin, wherein each measurement is automatically taken at a different position across the surface of the skin, and the method further comprises generating a map of the measured water content or a parameter based on the measured water content, the map corresponding to the plane of the surface. Huang also fails to show laterally translating the relative positions of the skin and of the delivery and collection optics so that each measurement is taken at a different position across the surface of the skin; and a positioner, wherein the positioner is an automated x-y positioning stage arranged to laterally translate the relative positions of the skin and of the delivery and collection optics.
Huang fails to show wherein the entry and collection regions are disposed on opposite sides of the sub-surface tissue; separately detecting said one or more spectral features in the collected probe light for each of a plurality of different spatial offsets between said entry and collection regions; wherein measuring water content of the sub- surface tissue from the spectral features comprises associating the spectral features from each of said plurality of different spatial offsets with a different depth or distribution of depth beneath the surface; combining said spectral features from said different spatial offsets to determine a separate measure of water content for each of one or more depths or distributions of depth beneath the surface; wherein the entry region comprises one or more segments which are located around a centrally disposed collection region; wherein the entry regions comprise an annulus disposed around the collection region; wherein the entry and collection regions are spatially offset by an offset in the range from 1 mm to 50 mm, and more preferably in the range from 3 mm to 20 mm; wherein the sub-surface tissue is beneath the surface of the subject by least twice the diffuse scattering transport length of probe light in the sub-surface tissue; wherein the sub-surface tissue is at least 2 mm beneath the surface of the subject.
Krishnan discloses medical compositions and Raman spectral analysis. Krishnan teaches using the one or more first spectral features normalized using the one or more second spectral features (normalizing the spectra to the C—H stretch band at 2800; [0275]-[0276]).
Gambhir discloses molecular imaging of living subjects using Raman spectroscopy. Gambhir teaches carrying out repeated measurements through the skin, of a parameter in the sub-cutaneous tissue, at least 2 mm beneath the surface of the skin, wherein each measurement is automatically taken at a different position across the surface of the skin and the method further comprises generating a map of the measured parameter, the map corresponding to the plane of the surface ([0072], [0096], [0118]). Gambhir also teaches laterally translating the relative positions of the skin and of the delivery and collection optics so that each measurement is taken at a different position across the surface of the skin ([0072], [0096], [0118]); and a positioner, wherein the positioner is an automated x-y positioning stage arranged to laterally translate the relative positions of the skin and of the delivery and collection optics ([0072], [0096], [0118]).
Bechtel discloses Raman spectroscopy of human tissue. Bechtel teaches the collection region being spatially offset from the entry region by an offset in the range of 1 mm to 50 mm ([0072]); wherein the entry and collection regions are disposed on opposite sides of the sub-surface tissue ([0043]); separately detecting said one or more spectral features in the collected probe light for each of a plurality of different spatial offsets between said entry and collection regions ([0043], [0050], [0069]-[0072]); wherein measuring water content of the sub- surface tissue from the spectral features comprises associating the spectral features from each of said plurality of different spatial offsets with a different depth or distribution of depth beneath the surface ([0050], [0069]); combining said spectral features from said different spatial offsets to determine a separate measure of water content for each of one or more depths or distributions of depth beneath the surface ([0050], [0069]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Huang to use the first spectral features normalized using the second spectral features as taught by Krishnan, in particular normalizing according to particular Raman peaks associated with the C—H stretch band at 2800, in order to more easily visualize the desired diagnostic information. The examiner notes that Huang obtains information of both the Raman OH stretch bands corresponding with water and information of the Raman C—H stretch bands, and broadly normalizes the acquired information using the area under the bands ([0221]). Huang recognizes the benefits of measuring in the FP and HW range, which includes both water type information as well as C—H type information ([0153]).
The examiner further notes that the end result of the measurements of Huang ultimately includes a measurement of the water content in combination with measurements of other biological parameters. This type of water content measurement meets the limitations as claimed.
One of ordinary skill in the art would recognize that a variety of different suitably equivalent means of processing acquired data to produce diagnostic data are known in the art, such as different ways of normalizing data, and any particular processing scheme may be utilized as desired by one of ordinary skill in the art to obtain the desired diagnostic information without undue experimentation. Krishnan in particular teaches normalizing the acquired data using the specific claimed C—H stretch band ([0275]-[0276]). While Huang uses a broader normalization scheme, it would be obvious to utilize a narrower normalization scheme as taught by Krishnan, for example which normalizes the data using any one specific band, such as the C—H stretch band as taught by Krishnan.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Huang and Krishnan to perform measurements through the patient’s skin at different positions using a x-y translation stage as taught by Gambhir, as Huang teaches that Raman spectroscopy of water is not limited to endoscope type embodiments and may be utilized for external measurements through the skin of the patient ([0251], [0266]), and as external measurements may be desirable in that they are less invasive to the patient. Furthermore, the use of an automated stage allows for the imaging device to be more accurately positioned over the region of interest to be sampled, as opposed to manually moving the imaging device by hand, thereby producing higher quality images of the region of interest.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Huang, Krishnan, and Gambhir to arrange the entry and collection regions on opposite sides of the tissue and to collect the light with spatial offsets between entry and collection regions as taught by Bechtel, as Bechtel teaches that light can be delivered to and collected from the tissue in a variety of different geometries in order to successfully collect Raman spectroscopic information of the tissue ([0043]). Bechtel further teaches that offsetting a detector for the Raman signal can have additional benefits including increasing the depth of sample from which the Raman light can be detected ([0050]).
Given these teachings, it would have been an obvious design choice to one of ordinary skill in the art to collect Raman spectroscopic information from a region of the patient’s tissue, where the region includes: wherein the entry region comprises one or more segments which are located around a centrally disposed collection region; wherein the entry regions comprise an annulus disposed around the collection region; wherein the entry and collection regions are spatially offset by an offset in the range from 1 mm to 50 mm, and more preferably in the range from 3 mm to 20 mm; wherein the sub-surface tissue is beneath the surface of the subject by least twice the diffuse scattering transport length of probe light in the sub-surface tissue; wherein the sub-surface tissue is at least 2 mm beneath the surface of the subject;
as it would be within the level of one of ordinary skill in the art to select/define the region to be sampled depending on various characteristics such as depending on the particular dimensions of the cancerous tumor unique to the patient or the user’s preference in selecting a region to be treated such as cancerous tissue and a safety margin around the cancerous region, and would be accomplished by one of ordinary skill in the art without undue experimentation.
Claim(s) 32 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang (US 2017/0138860) in view of Krishnan et al. (US 2008/0213215; hereinafter Krishnan), Gambhir (US 2010/0166650; hereinafter Gambhir), and Bechtel et al. (US 2012/0203114; hereinafter Bechtel).as applied to claims 1 and 25 above, and further in view of Alfano et al. (US 6665556; hereinafter Alfano).
Huang fails to show wherein the probe light directed to the entry region is laser light with a wavelength of between 630 nm and 720 nm.
Alfano discloses methods and apparatus for examining tissue using spectroscopy. Alfano teaches wherein the probe light directed to the entry region is laser light with a wavelength of between 630 nm and 720 nm (column 4, lines 17-50; column 7, lines 28-37; column 8, lines 5-24).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the combined invention of Huang, Krishnan, Gambhir, and Bechtel to utilize an exciting wavelength between 630 nm and 720 nm as taught by Alfano, as Alfano teaches that exciting the tissue at such wavelengths will yield diagnostic information in order to characterize cancerous tissue (column 4, lines 17-50).
Response to Arguments
Applicant's arguments filed 8/20/25 have been fully considered but they are not persuasive.
In response to applicant’s arguments that Huang cannot measure 2 mm beneath the surface of the skin, examiner respectfully disagrees. Huang teaches measuring is not limited to endoscopic applications, and includes measurement of skin ([0266]). Applicant further argues that Huang teaches measurement of the skin as an “organ”, however, the examiner notes that human skin is comprised of multiple layers beneath the surface of the skin, where the multiple layers of the skin include epidermis, dermis, subcutaneous layers, where the layers of the skin includes depths 2 mm beneath the surface.
In response to applicant’s arguments regarding the combination of Huang and Bechtel, examiner respectfully disagrees. The examiner maintains that Bechtel teaches that source-detector spacing is a known variable in the design of optical imaging systems. A variety of source detector spacing and configurations may be utilized, including concentric designs, and Bechtel teaches that it is known to space the source and detector by an offset in the range from 1 mm to 50 mm ([0072]). Bechtel further teaches that offsetting a detector for the Raman signal can have additional benefits including increasing the depth of sample from which the Raman light can be detected ([0050]). In response to applicant’s arguments that one of ordinary skill in the art would be incapable of modifying Huang in such a manner, examiner respectfully disagrees. A wide range of different optical imaging probe designs are known in the art. It is within the level of one of ordinary skill in the art, given the different diagnostic applications of Huang including skin measurement ([0266]), to modify the imaging probe appropriately for use outside of endoscopic applications. Furthermore, the examiner notes that human skin is comprised of multiple layers beneath the surface of the skin, where the multiple layers of the skin include epidermis, dermis, subcutaneous layers, where the layers of the skin includes depths 2 mm beneath the surface. As Huang teaches skin measurement, one of ordinary skill in the art would recognize that it would be desirable modify the source detector separation to enable a skin type measurement.
In response to applicant’s arguments regarding Gambhir, examiner respectfully disagrees. The examiner maintains that the teachings of Gambhir may be appropriately combined with Huang.
Gambhir is relied upon to teach: “carrying out repeated measurements through the skin, of a parameter in the sub-cutaneous tissue, at least 2 mm beneath the surface of the skin, wherein each measurement is automatically taken at a different position across the surface of the skin and the method further comprises generating a map of the measured parameter, the map corresponding to the plane of the surface ([0072], [0096], [0118]). Gambhir also teaches laterally translating the relative positions of the skin and of the delivery and collection optics so that each measurement is taken at a different position across the surface of the skin ([0072], [0096], [0118]); and a positioner, wherein the positioner is an automated x-y positioning stage arranged to laterally translate the relative positions of the skin and of the delivery and collection optics ([0072], [0096], [0118]).”
The cited teachings of Gambhir may be applied to a wide variety of generic optical imaging techniques. A wide variety of different optical imaging techniques carry out repeated measurements to obtain a map using an automated x-y positioning stage. These features are not specific to any particular type of Raman imaging.
In response to applicant’s arguments that Gambhir fail to teach detecting water content, the examiner notes that this feature is taught by the base reference Huang. There is no requirement for Gambhir to teach detecting water content. Gambhir is within the field of optical imaging and may be appropriately combined.
In response to applicant’s arguments that it would not be obvious to combine the teachings of Krishnan, examiner respectfully disagrees. Krishnan discloses Raman spectral analysis techniques. Krishnan teaches using the one or more first spectral features normalized using the one or more second spectral features. The benefits of normalizing are known in the spectroscopic arts. The examiner maintains that it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Huang to use the first spectral features normalized using the second spectral features as taught by Krishnan, in particular normalizing according to particular Raman peaks associated with the C—H stretch band at 2800, in order to more easily visualize the desired diagnostic information. The examiner notes that Huang obtains information of both the Raman OH stretch bands corresponding with water and information of the Raman C—H stretch bands, and broadly normalizes the acquired information using the area under the bands ([0221]). Huang recognizes the benefits of measuring in the FP and HW range, which includes both water type information as well as C—H type information ([0153]).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
THIS ACTION IS MADE FINAL. 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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/JONATHAN CWERN/Primary Examiner, Art Unit 3797