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 .
Response to Arguments
Applicant respectfully submits that the prior art does not teach defocusing the microscope from a determined monolayer focus level to obtain off focus images. Examiner respectfully disagrees. D1 explicitly teaches in ¶ 39 capturing a focused image of the monolayer and subsequently obtaining off-focus images by shifting relative to the focused position (see ¶ 39: “plurality of different focal distances may be predefined, or may be set by separating the focal distance by a predefined distance before and after from the auto-focus position based on the auto-focus position”). Applicant further submits that the combination of D1 and D2 would not have obvious. The argument is moot in view of the new grounds of rejection.
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 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.
Claims 1-11, 15-21 are rejected under 35 U.S.C. 103 as being unpatentable over D21 and further in view of D1.2
With regard to claim 1, D2 teach method for use with a cell suspension, the method comprising: allowing, for a predefined time interval, some cells within the cell suspension to settle such as to form a monolayer (see abstract, fig. 7, p. 2528-2529: monolayer cell suspension settles or relaxes overtime); acquiring images of the monolayer and determining a property of at least a portion of the cell suspension (see abstract, fig. 2: acquiring images of the monolayer to examine cell morphology and subcellular organization).
D2 teaches imaging a monolayer, but fails to explicitly teach acquiring focus image and off-focus images to determine properties of the monolayer, however D1 teach the missing limitations.
D1 teaches method for use with a bodily sample that contains cells (see fig. 3), determining a monolayer focus level at which to focus a microscope such that the monolayer is in focus, and focusing a microscope such that a focal plane of the microscope at least approximately coincides with the monolayer level (see ¶ 39: “plurality of different focal distances may be predefined, or may be set by separating the focal distance by a predefined distance before and after from the auto-focus position based on the auto-focus position” – auto-focus position read as the focal plane where the monolayer is in focus; see fig. 3: imaging cell monolayer, i.e., cells are not stacked but are next to each other); acquiring at least one on-focus microscopic image of the sample, while the focal plane of the microscope approximately coincides with the monolayer level (see ¶ 39: “plurality of different focal distances may be predefined, or may be set by separating the focal distance by a predefined distance before and after from the auto-focus position based on the auto-focus position” – auto-focus position read as the focal plane where the monolayer is in focus); focusing the microscope such that the focal plane of the microscope is offset with respect to the monolayer level (see ¶ 39: plurality of focal planes, where at least one focal plane is offset with another focal plane of the monolayer level); acquiring at least one off-focus microscopic image of the sample, while the focal plane of the microscope is offset with respect to the monolayer level (see ¶ 39); and determining a property of at least a portion of the sample, at least partially based upon the on-focus and off-focus images (see figs. 4, 6, ¶¶ 39, 40-45).
One skilled in the art before the effective filing date would have found it obvious to combine the teachings to arrive at the claimed invention. D2 teaches generating a suspended monolayer of cells for imaging and analysis of the monolayer. Separately, D1 teaches the technique of acquiring an on-focus and off-focus images of a monolayer to analyze the cells. It would have been obvious to substitute the imaging in D2 with the imaging techniques described by D1, yielding predictable and enhanced results. By capturing images at plurality of focal positions, analysis of the cells may be enhanced as described in D1.
With regard to claim 2, D1 teach wherein acquiring at least one off-focus microscopic image of the sample while the focal plane of the microscope is offset with respect to the level comprises acquiring at least one off-focus microscopic image of the sample while the focal plane of the microscope is offset with respect to the level by a predetermined offset (see fig. 3, ¶ 39).
With regard to claim 3, D1 teach wherein determining a property of at least a portion of the sample at least partially based upon the on-focus and off-focus image comprises inputting the on-focus and off-focus image into a machine-learning classifier, the machine- learning classifier being configured to determine a property of at least a portion of the sample at least partially based upon the on-focus and off-focus image (see fig. 3, 4-6, ¶¶ 40-45: machine learning for determining cell features or parameters).
With regard to claim 4, D1 teach wherein determining a property of at least a portion of the sample at least partially based upon the on-focus and off-focus image comprises deriving one or more parameters from the on-focus and off-focus image and inputting the one or more derived parameters into a machine-learning classifier, the machine-learning classifier being configured to determine a property of at least a portion of the sample at least partially based upon the derived parameters (see ¶¶ 40-45, 50: cell features and parameters).
With regard to claim 8, D1 teach wherein focusing the microscope such that the focal plane of the microscope is offset with respect to the level comprises focusing the microscope such that the focal plane of the microscope is set closer to an objective lens of the microscope than the level at which at least some cells belonging to the sample are at least partially disposed (see ¶ 39: capturing at different focal positions where the focal plane is closer or farther away from the objective lens).
With regard to claim 9, D1 teach wherein focusing the microscope such that the focal plane of the microscope is offset with respect to the level comprises focusing the microscope such that the focal plane of the microscope is set farther from an objective lens of the microscope than the level at which at least some cells belonging to the sample are at least partially disposed (see ¶ 39: capturing at different focal positions where the focal plane is closer or farther away from the objective lens).
With regard to claim 11, D1 teach wherein focusing the microscope such that the focal plane of the microscope is offset with respect to the level comprises focusing the microscope such that the focal plane of the microscope is offset with respect to the level at which at least some cells belonging to the sample are at least partially disposed by between one and five depths of focus of the microscope (see fig. 3: depth of focus being about 1 micron).
With regard to claim 15, D1 teach wherein the sample includes a blood sample, and
wherein determining the property of the portion of the sample at least partially based upon the on-focus and off-focus image comprises identifying one or more entities within the blood sample at least partially based upon the on-focus and off-focus image, the one or more entities selected from the group consisting of: a platelet, a leukocyte, a lymphocyte, a granulocyte, a monocyte, a neutrophil, a banded neutrophil, an eosinophil, a basophil, and a macrophage (see fig. 3, ¶¶ 40, 50: lymphoid cell).
With regard to claim 18, D1 teach wherein determining the property of the portion of the sample at least partially based upon the on-focus and off-focus image further comprises estimating a parameter of the one or more entities at least partially based upon the identified outlines, the parameters selected from the group consisting of: cell area and cell volume (see fig. 3, ¶¶ 37, 43-45: cell identification and size estimation, read as area).
With regard to claim 20, see discussion of claim 1. D2 further teaches a processor (see fig. 2: computer).
With regard to claim 21, see discussion of claim 1. D1 further teaches at least partially based upon the off-focus image, identifying an entity disposed within the monolayer focus level (see figs. 4, 6, ¶¶ 39, 40-45).
With regard to claim 5, D1 fails to explicitly teach wherein the sample includes a blood sample, and wherein acquiring at least one off-focus microscopic image of the sample while the focal plane of the microscope is offset with respect to the level comprises acquiring at least one off-focus microscopic image of the sample with the sample illuminated with light having a wavelength of between 505 nm and 535 nm, however Examiner takes Official Notice to the fact that using wavelength between 505 and 535 nm is well known in the art before the effective filing date and would have been particularly obvious to incorporate known teachings into the configuration of D1 yielding predictable and enhanced identification or classification different cells and cellular parts.
With regard to claim 6, D1 fails to teach wherein the sample includes a blood sample, and
wherein acquiring at least one off-focus microscopic image of the sample while the focal plane of the microscope is offset with respect to the level comprises acquiring at least one off-focus microscopic image of the sample with the sample illuminated with light having a wavelength of between 400 nm and 450 nm, however Examiner takes Official Notice to the fact that using wavelength between 400 and 450 nm is well known in the art before the effective filing date and would have been particularly obvious to incorporate known teachings into the configuration of D1 yielding predictable and enhanced identification or classification different cells and cellular parts.
With regard to claim 7, D1 fails to explicitly teach wherein the sample includes a blood sample, and wherein acquiring at least one off-focus microscopic image of the sample while the focal plane of the microscope is offset with respect to the level comprises acquiring at least one off-focus microscopic image of the sample with the sample illuminated with light having a wavelength of between 620 nm and 640 nm, however Examiner takes Official Notice to the fact that using wavelength between 400 and 450 nm is well known in the art before the effective filing date and would have been particularly obvious to incorporate known teachings into the configuration of D1 yielding predictable and enhanced identification or classification different cells and cellular parts.
With regard to claim 10, D1 teach wherein focusing the microscope such that the focal plane of the microscope is offset with respect to the level comprises focusing the microscope such that the focal plane of the microscope is offset with respect to the level at which at least some cells belonging to the sample are at least partially disposed by between -1 micron and 1 micron (see fig. 3) but fail to explicitly teach between 20 microns and 100 microns. However, Examiner takes Official Notice to the fact that it is well known before the effective filing date to focus the images at depths between 20 and 100 microns and would have been particularly obvious to incorporate known teachings into the configuration of D1 yielding predictable results. The motivation would have been to image cell samples comprising plurality of layers disposed between a range of microns.
With regard to claim 16, D1 teaches wherein the sample includes a blood sample, and
wherein determining the property of the portion of the sample at least partially based upon the on-focus and off-focus image comprises identifying a see fig. 3, ¶¶ 39, 40-45, 50). D1 fails to explicitly teach blast cells, however one skilled in the art would have found it obvious to apply the teachings of D1 to different cells, such as blast cells.
With regard to claim 17, D1 teach wherein determining the property of the portion of the sample at least partially based upon the on-focus and off-focus image comprises identifying see fig. 3, ¶¶ 37, 43-45: cell identification and size estimation). D1 fails to explicitly teach determining the outline, however Examiner takes Official Notice to the fact that it is well known in the art to determine outlines or boundaries of cells, and it would have been particularly obvious to incorporate known teachings into the configuration D1 yielding predictable and enhanced estimation of cell size based on precise outlines or boundaries.
With regard to claim 19, D1 teach herein determining the property of the portion of the sample at least partially based upon the on-focus and off-focus image further comprises estimating a parameter of sample at least partially based upon the identified outlines, the at least one parameter selected from the group consisting of: see fig. 3, ¶¶ 37, 43-45: cell identification and size estimation). D1 fails to explicitly teach estimating mean cell are or cell volume, however Examiner takes Official Notice to the fact that it is well known before the effective filing date to count cells, determine cell area or volume of cells and estimating mean cell area or mean volume, and it would have been particularly obvious to incorporate known teachings in to the configuration of D1 yielding predictable results. The motivation for determining mean cell area or volume would have been to enhance the classification of cells and improve diagnosis based on the average area or average volume.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over D1 and D2 and further in view of D33.
With regard to claim 14, D2 and D1 fail to teach wherein determining the property of the portion of the sample, at least partially based upon the on-focus and off-focus image comprises normalizing the on-focus and off-focus image with respect to each other and determining the property of the portion of the sample, at least partially based upon the normalization, however D3 teaches the missing feature (see col 30 lines 50-55: normalization of images). One skilled in the art before the effective filing date would have found it obvious to combine the teachings to arrive at the claimed invention. In particular, it would have been obvious to incorporate known teachings of normalization of images as taught by D3 into the configuration of D1 and D2 yielding predictable and enhanced analysis of image features.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AVINASH YENTRAPATI whose telephone number is (571)270-7982. The examiner can normally be reached on 8AM-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sumati Lefkowitz can be reached on (571) 272-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AVINASH YENTRAPATI/Primary Examiner, Art Unit 2672
1 Harris, Andrew R., et al. "Generating suspended cell monolayers for mechanobiological studies." Nature protocols 8.12 (2013): 2516-2530.
2 US Publication No. 2015/0124082.
3 US Patent No. 10,488,644.
Prosecution Insights