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
Claims 1-15 are 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.
Regarding the third limitation of claims 1, it is not clear what is being differentiated between the first and second Raman scattered signals. Furthermore, it is not clear how or what aspect of the first and second optical images are being transformed. Correction is required.
With regard to claims 7 and 14, it is not clear what is being differentiated between the third and fourth Raman scattering. Furthermore, it is not clear how or what aspect of the third and fourth optical images are being transformed. 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.
Claim(s) 1-4 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ambardar et al.
(Quantum Leap from Gold and Silver to Aluminum Nanoplasmonics for Enhanced Biomedical Applications)
in view of Canpolat (W02005092194) further in view of Hayazawa et al. (Metallized Tip Amplification of Near-Field Raman Scattering).
With respect to claim 1, Ambardar teaches a method for forming at least a first image by scattering and absorption of radiation, see page 4, §2.2.2. Ambardar identifies the use of Al (Aluminum) nanoparticles and metamaterial substrates can be used for medical treatment (see Introduction at line 4). It is well known that Al and Ag have plasmonic properties that have applications on human cells and tissues, see page 4, § 2.2.4. Ambardar also teaches using passive substrates, such as Silver (Ag) substrates (see the Introduction, second para.) At page 9, lines 1-6, Ambardar teaches that Al and Ag, among others substrates, can be combined with smart optical techniques, using Raman spectroscopy, for the purpose of developing a routine and affordable diagnostic tool. Therefore, this corresponds with the generation of scattered images using light scattered onto different substrates as claimed. At the bottom of page 5, Ambardar teaches the use of Au, Ag and Al nanostructures, where at least two were used to enhance Raman signals of bacteria.
Ambardar teaches all of the subject matter except for differentiating between the interior of the cell and the membrane of the cell. At § 3.1, page 5, beginning at line 10, Ambardar teaches that plasmonic nanostructures have been used in surface enhanced Raman scattering.
Canpolat teaches an invention for detecting cancerous cells using elastic scattering signals (see page 3, second full para.) At page 3, third para., Canpolat teaches light scattering in a tissue occurs at cell membrane, nuclei and other organelles in a cell. Also in the same paragraph, Canpolat teaches that “… Light is also scattered inside a cell by nucleus; mitochondria and other organelles due to difference in index of refraction between intracellular compartments and surrounding cytoplasm.” Hence, Canpolat teaches scattering the epithelial of the cell as well as the inner organelles of the cell in the manner claimed.
Since Ambardar and Canpolat are both directed to celluar microscopy, the purpose of acquiring images of the cell from two different regions of the cell by two different substrates (for example, Al and Ag) would have been recognized by Ambardar as set forth by Canpolat. Moreover, the acquisition of the images with regard to inner and outer portions of the cellular structure is taught by Canplat and would have been recognized by Ambardar.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use the Nanoplasmoics taught by Ambardar but to apply them to cellular structures in the same manner as Canpolat for the purpose of differentiating the cellular structure as having content such as normal or cancerous cells.
Neither Ambardar nor Canpolat teach the use of force images that have been acquired using a force microscope.
Hayazawa teaches using a tip to amplify a near-field Raman scattering, wherein the Raman scattering device is of an atomic force microscope, (See the Abstract).
Since, Hayazawa teaches the use of an atomic force microscope to generate Raman scattering, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify or replace the type of Raman spectroscope used by Ambardar or Canpolat with the specific force microscope for purpose of differentiating between cancerous and normal cells as a matter of design choice.
With regard to claim 2, Ambardar teaches biologic cel cultures of cancerous cells, see page 8, second full paragraph. Canpolat teaches biologic cell cultures of cancerous cells, see paras. 3-11. The motivation for this rejection is the same as that to claim 1.
With respect to claim 3, Canpolat teaches use of a broadband light source to irradiate tissue and collect back scattered light and is not intended to destroy cells. Furthermore, Canpolat describes the process as being a non-invasive diagnostic for cancer (see Description at para. 4). Hence, the cellular structure is not touched. The motivation for this rejection is the same as that to claim 1.
With respect to claim 4, Ambardar in view of Canpolat teaches all of the subject matter except for subtracting first and second optical images.
Hayazawa teaches subtracting a first far-field spectra from a near-field spectra. The result of the subtraction is illustrated by figure 4. Since Hayazawa provides the motivation for subtracting a first optical image from the second, the purpose of subtracting images would have been recognized by Ambardar in view of Canpolat as set forth by Hayazawa.
It would have been obvious to transform first and second optical images to generate an Enhancement Factor for enhancing the signals from Raman scattering for at least the same reason identified by Hayazawa, that the difference to show enhancements at peaks identified by figure 4a and explained in the first full paragraph at page 336.
With respect to claim 11, the claim recites aluminum nanoparticles with random distributions of up to or in excess of 50nm.
Ambardar teaches aluminum distributions of nanoparticles substrates which may be used to optimize the near-field enhancement and spectral response by varying the nanoparticle sizes (See section 2.1 at page 2 and Figure 1). Random distribution of sizes are shown by Figure 1 with wavelengths from 250-650 nm on the supporting aluminum substrates.
Ambardar further teaches the use of aluminum nanoparticles on human cells and tissue (See §2.2.4). See also §2.2.2, second para. where the scattering mechanism leads to near-field enhancement with the corresponding increase of the local surface. The motivation for this rejection is the same as that to claim 1.
Claim(s) 5, 6 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ambardar in view of Canpolat as set forth by Hayazawa further in view of KSR v. Teleflex 550 U.S. 398 (2007).
With respect to claim 5, Ambardar in view of Carpolat as set forth by Hayazawa teaches all of the subject matter claimed except for acquiring images of the cell membrane only.
Hayazawa teaches scanning each of the cell membrane, the nucleus, intracellular compartments and surrounding cytoplasm. Hayazawa also points out that the index of refraction for cell membranes is greater than the index of refraction for extra cellular liquid. Hence, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to try other imaging techniques to accomplish variable depth perception while imaging.
It would have been obvious to try a scattering technique using spectrometers where the depth adjustment or focus points cover a range of the thickness of the membrane so as to avoid focus on extraneous images other than the cell membrane (i.e, cytoplasms and cellular fluids).
With respect to claim 6, the claim now recites the generation of a plasma membrane. The Examiner contends that the plasma membrane are the fluids within the cell membrane. Hayazawa clearly teaches imaging the fluids within the membrane. At para. 8 of page 3, Hayazawa teaches performing light scattering on other organelles of the cell structure and specifically mentions cellular liquid (see line 3). Hence, the Examiner reads the plasma as the cellular liquid.
The motivation for the rejection is the same as to claim 5
With respect to claim 12, Ambardar in view of Canpolat teaches all of the subject matter except for subtracting first and second optical images.
Hayazawa teaches subtracting a first far-field spectra from a near-field spectra. The result of the subtraction is illustrated by figure 4. Since Hayazawa provides the motivation for subtracting a first optical image from the second, the purpose of subtracting images would have been recognized by Ambardar in view of Canpolat as set forth by Hayazawa.
It would have been obvious to transform first and second optical images to generate an Enhancement Factor for enhancing the signals from Raman scattering for at least the same reason identified by Hayazawa, that the difference to show enhancements at peaks identified by figure 4a and explained in the first full paragraph at page 336.
With regard to the limitation of generating a target of the only the membrane without disturbing the content of the cell,
Hayazawa teaches scanning each of the cell membrane, the nucleus, intracellular compartments and surrounding cytoplasm. Hayazawa also points out that the index of refraction for cell membranes is greater than the index of refraction for extra cellular liquid. Hence, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to try other imaging techniques to accomplish variable depth perception while imaging.
It would have been obvious to try a scattering technique using spectrometers where the depth adjustment or focus points cover a range of the thickness of the membrane so as to avoid focus on extraneous images other than the cell membrane (i.e, cytoplasms and cellular fluids).
Allowable Subject Matter
Claims 7-10 and 13-15 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Claim 7 is objected as containing allowable matter since the prior art does not teach or suggest in claimed combination, using a third Raman scattering signal by an interior of an auxiliary cell and a fourth Raman scattering signal by a membrane of the auxiliary cell and generating a non-cancerous target image representing only the membrane of the auxiliary cell of the auxiliary cell.
Claim 8 is objected to as being allowable, subject to the 112 rejection above, based on its dependence from claim 7.
Claim 9 is objected to as being allowable for the reason the prior art does not show in claimed combination, the assignment of a first lipid to protein ratio at a first portion of the membrane identifying a first marker; assigning a second lipid to protein ratio on a second portion of the membrane different from the first, identifying a second marker and using the first and second biomarkers to identify changes in molecular composition to identify cancer.
Claim 10 is objected to as allowed based on its dependency from claim 9.
Claim 13 is objected to as containing allowable matter for the reason the prior art does not show the assignment of a first lipid to protein ratio at a first portion of the membrane identifying a first marker; assigning a second lipid to protein ratio on a second portion of the membrane different from the first, identifying a second marker and using the first and second biomarkers to identify changes in molecular composition to identify cancer.
Claim 14, is objected as containing allowable matter since the prior art does not teach or suggest in claimed combination, using a third Raman scattering signal by an interior of an auxiliary cell and a fourth Raman scattering signal by a membrane of the auxiliary cell and generating a non-cancerous target image representing only the membrane of the auxiliary cell of the auxiliary cell.
Claim 15 is objected to as containing allowable matter since the prior art does not teach or suggest in claimed combination,
the assignment of a first lipid to protein ratio at a first portion of the membrane identifying a first marker; assigning a second lipid to protein ratio on a second portion of the membrane different from the first, identifying a second marker and using the first and second biomarkers to identify changes in molecular composition to identify cancer.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEROME GRANT II whose telephone number is (571)272-7463. The examiner can normally be reached M-F 9:00 a.m. - 5:00 p.m..
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/JEROME GRANT II/Primary Examiner, Art Unit 2664