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 .
Status of Claims
The claim set submitted on 30 JANUARY 2023 is acknowledged and considered. In the claim set, consisting of four (4) pages, Claims 1-18 are presented.
Current pending claims are Claim 1-18 and are considered on the merits below.
Specification
The disclosure is objected to because of the following informalities:
The use of the term PHANTOM™, page 26, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
On page 38, line 8, there is a close parenthesis, but there is not an open parenthesis.
Claim Objections
Claim 8 is objected to because of the following informalities: In the instance of “plug of length L”; the reference character “L” should be offset by parenthesis or by commas. In addition the insta. Appropriate correction is required.
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.
Claims 1-18 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.
Claim 1 recites the limitation "inlet channel" and "outlet channel". There is insufficient antecedent basis for this limitation in the claim. Only a "fluidic input channel" and "fluidic output channels" are positively claimed.
Claims 2-18 are also rejected under 112(b) and being dependent upon a base claim rejected under 112(b).
Claims 7 and 8 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.
Claim 7 and 8 recites the limitation "inlet channel" . There is insufficient antecedent basis for this limitation in the claim. A "fluidic input channel" was claim first in Claim 1.
In Claim 8, the language recites “wherein W”. There is insufficient antecedent basis for this limitation in the claim. W is not defined.
In Claims 9, 14, 15 and 16, the claim recites “outlet channels”. There is insufficient antecedent basis for this limitation in the claim. A "fluidic output channels" was claim first in Claim 1.
The term “primarily” in claim 14 is a relative term which renders the claim indefinite. The term “primarily” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 17 recites the limitation "each outlet" . There is insufficient antecedent basis for this limitation in the claim. An outlet is not positively claimed in a fluidic splitter.
In regards to Applicant’s use of inlet/input or outlet/output, Applicant should review the original disclosure and determine which term should be used in the entire claim set. No new matter should be added.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, and 5-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BLAUCH, PNAS, July 11, 2017, vol. 114, no. 28, pages 7283-7288, as evidence by the Supporting Information, Blauch et al. 10.1073/pnas.1705059114, herein referred ‘Supporting Information’.
Applicant’s invention is directed towards a method.
Regarding Claim 1, the method for splitting a biological sample, abstract, bisecting cells, the method comprising:
splitting a biological sample in a fluidic apparatus; wherein the fluidic apparatus includes a fluidic input channel and two fluidic output channels, Figure 1A, 1B, page 7284, Design and Validation…, and
wherein the inlet channel and the outlet channels meet at a Y-junction where the inlet channel is in fluid communication with the two outlet channels, Figure 1A, 1B, page 7284, Design and Validation…, Supporting Information Figure S1; wherein an interior tip of the Y-junction is a blade configured to split the biological sample from the fluidic inlet channel into substantially two parts while fluid flows through the Y-junction,, Figure 1A, page 7284, Design and Validation…, the knife consisting of a blade…, Supporting Information Figure S1, and to deliver the two parts separately to the two fluidic outlet channels, Figure 1A, 1B, page 7284, Design and Validation…; wherein the biological sample includes one or more biological structures selected from the group consisting of: cells, organoids, tissues, and multi-cell structures, page 7283, Introduction section and Box “Significance”, Supporting Information page 1; and
wherein the blade is configured to split one or more biological cells of the one or more biological structures in operation, Figure 1A, 1B, page 7284, Design and Validation…, Figure 2A, page 7286, Supporting Information Figure S1 .
Additional Disclosures Included are: Claim 2: wherein the method of claim 1, wherein a flow rate of fluid through the apparatus is selected such that the biological sample is locally cut by the blade to provide the two parts, Figure 1B, 1C, page 7284, Design and Validation…, Supporting Information Figure S1; Claim 3: wherein the method of claim 1, wherein the biological sample is a single cell, abstract, page 7283, Figure 1C, single cell cut by instant device, Supporting Information page 1, Microchannel Fabrication and Injection… ; Claim 5: wherein the method of claim 1, wherein an outlet split ratio of the fluidic apparatus is between 60:40 and 40:60, Figure 1A, 1B, 2A, page 7284, Design and Validation…., Supporting Information, page 1 and 2, Measurement of Evenness of Cut, Figure S1 ; Claim 6: wherein the method of claim 1, wherein an angle of the blade is 40 degrees or less, Figure 1A, 1B, 2A, page 7284, Effect of Applied,….Figure 4, Supporting Information, Figure S1; Claim 7: wherein the method of claim 1, wherein the fluidic inlet channel is sized to control a position of the biological sample while still permitting fluid flow and movement of the biological sample through the fluidic apparatus, page 7284, Design and Validation…Figure 1A, 4, Supporting Information Table S1. ; Claim 8: wherein the method of claim 1, wherein the fluidic inlet channel is sized such that the biological sample in the fluidic inlet channel forms a plug of length L in the fluidic inlet channel, wherein W is a largest lateral dimension of the fluidic inlet channel, and wherein L is 1.1 W or more., page 7284, Design and Validation…Figure 1A, 4, Supporting Information Table S1. ; Claim 9: wherein the method of claim 1, wherein the fluidic outlet channels expand in cross-section at the Y-junction, Figure 1A, Supporting Information Movies S2-S4, Figure S3, and wherein a total width of the two fluidic outlet channels after this expansion is greater than or equal to a width of the fluidic inlet channel, Figure 1A, Supporting Information Movies S2-S4, Figure S3. ; Claim 10: wherein the method of claim 1, wherein the Y-junction is disposed in a plane and wherein the blade is formed by a vertical edge of the Y-junction that is perpendicular to the plane, Figure 1A, page 7284, Design and Validation….; Claim 11: wherein the method of claim 1, wherein the Y-junction is disposed in a plane and wherein the blade is formed by a non-vertical edge of the Y-junction that is oblique to the plane, Figure 1A, page 7284, Design and Validation….; Claim 12: wherein the method of claim 1, wherein the blade has a predetermined micro-roughness at or in proximity to a cutting edge of the blade, Figure 1A, page 7284, Design and Validation….; Claim 13: wherein the method of claim 1, wherein a Young's modulus of the blade is at least 10x greater than a Young's modulus of the biological sample, Figure 1A, page 7284, Design and Validation…. Note: It is known in the art that the Young’s modulus of PDMS is typically from 0.5 MPa to 2.97 MPa and depending on the type of cells, it be as low as 1 kPa; and Claim 14: wherein the method of claim 1, wherein an outlet split ratio of the fluidic apparatus is determined primarily by relative flow rates in the fluidic outlet channels, Figure 2, page 7284, Effect of Applied Viscous Stress…
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.
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.
Claims 4, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over BLAUCH, PNAS, July 11, 2017, vol. 114, no. 28, pages 7283-7288, as evidence by the Supporting Information, Blauch et al. 10.1073/pnas.1705059114, herein referred ‘Supporting Information’
Regarding Claim 4, the reference BLAUCH discloses the claimed invention, but is silent in regards to wherein the biological sample is a multi-cell sample.
It should be noted that the instant claim does not further define the method, but rather defines what type sample is to be applied or used with the method.
Claim analysis is highly fact-dependent. A claim is only limited by positively recited elements. Thus, “[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935).
See also In re Casey, 370 F.2d 576, 152 USPQ 235 (CCPA 1967), “the manner or method in which such machine is to be utilized is not germane to the issue of patentability of the machine itself.”.
BLAUCH discloses the use of a single-cells, entire document.
However, since the instant claim does not further limit the method or add any addition step to the method, the type of biological sample to be used with / in the method is merely a design choice, and it would be obvious before the effective filing date to modify the method so that the biological sample is a multi-cell sample so that the cells from different samples can be studied for cellular heterogeneity and function. The use of multi-cells is a merely a design choice of the method and does not further define how the method is performed, but the use of a multi-cell sample can be used to analyze the effects of different factors on cell behavior and gene expression.
Regarding Claim 15, the reference BLAUCH discloses the claimed invention, but is silent in regards to wherein the relative flow rates in the fluidic outlet channels are determined by a lateral position of the blade within the fluidic inlet channel configured to make the Y-junction asymmetric.
In Figure 1A of BLAUCH the dimension of the blade is noted, wb. In Figure 2, the effected of applied flow rate is modified and the cutting process and cell survival is observed. In the Supporting Information, Table S1, the width of the outlet at the blade is listed, however, it would be obvious to one having ordinary skill in the art before the effective filing date to modify the wb value such that the relative flow rates in the fluidic outlet channels are determined by a lateral position of the blade within the fluidic inlet channel configured to make the Y-junction asymmetric to observe the effect of viscous stress and effect of cell deformation, page 7284-7285, and to observe the evenness of cut into fragments, page 1 and 2 of ‘Supporting Information’.
Regarding Claim 16, the reference BLAUCH discloses the claimed invention, but is silent in regards to wherein the relative flow rates in the fluidic outlet channels are determined by an asymmetric downstream fluidic configuration of the fluidic outlet channels.
However, BLAUCH discloses and shows in Figure 2, the effect of the applied flow rate / viscous stress is on cell deformation and survival, Figure 2, page 7284. The morphology of the cell was observed. BLAUCH teaches the threshold velocity has immediate practical value in guiding the choice of channel geometry, page 7285.
In the ‘Supporting Information’, Figure S3, the effect of flow rate was observed.
Since BLAUCH discloses the channel geometries have an effect on the threshold velocity, flow rates, it would be obvious to one having ordinary skill in the art before the effective filing date to modify the claimed invention so that the relative flow rates in the fluidic outlet channels are determined by an asymmetric downstream fluidic configuration of the fluidic outlet channels to optimize splitting or cutting of the cell with cell deformation and survival, page 7285, to observe the effect of viscous stress and effect of cell deformation, page 7284-7285, and to observe the evenness of cut into fragments, page 1 and 2 of ‘Supporting Information’.
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over BLAUCH, PNAS, July 11, 2017, vol. 114, no. 28, pages 7283-7288, as evidence by the Supporting Information, Blauch et al. 10.1073/pnas.1705059114, herein referred ‘Supporting Information’, and further in view of SUNDSTROM, US Patent 8,802,033 B2.
Applicant’s invention is directed towards a method.
Regarding Claim 17, the BLAUCH reference discloses a method for multiply dividing a biological sample, abstract, the method comprising:
performing the method of claim 1, See Rejection of Claim 1 above, in a fluidic configuration including two or more stages of fluidic splitters, abstract, Figure 4C, wherein each fluidic splitter includes a fluidic input channel and two fluidic output channels, and wherein the inlet channel and the outlet channels meet at a Y-junction where the inlet channel is in fluid communication with the two outlet channels; wherein an interior tip of the Y-junction of each fluidic splitter is a blade configured to split the biological sample from the fluidic inlet channel into substantially two parts while fluid flows through the Y- junction, and to deliver the two parts separately to the two fluidic outlet channels, Figure 1A, 1B, page 7284, Design and Validation ….
The BLAUCH reference discloses the claimed invention, but is silent in regards to wherein each outlet of a fluidic splitter of a prior stage is connected to an inlet of a fluidic splitter of a subsequent stage.
The SUNDSTROM reference disclose a method for splitting a biological sample, abstract, Figure 1 and 4, the method comprising: splitting a biological sample in a fluidic apparatus, abstract, Column 2 line 16-25, Figure 1 and 4; wherein the fluidic apparatus includes a fluidic input channel and two fluidic output channels, Figure 2, inlet is where ‘Fluid’ arrow is, outlet is considered to be after the first slicing unit and after the second slicing unit; and wherein the inlet channel and the outlet channels meet at a Y-junction where the inlet channel is in fluid communication with the two outlet channels, Column 3 line 57-Column 4 line 2, situation where slicing device has 1 microgrid; wherein an interior tip of a Y-junction, Figure 1, Y-junction is from left to right, biological material is spit into a Y after it is contact with slicing beam, is a blade configured to split the biological sample from the fluidic inlet channel into substantially two parts while fluid flows through the Y-junction, Column 3 line 57-Column 4 line 2, situation where slicing device has 1 microgrid, and to deliver the two parts separately to the two fluidic outlet channels, Column 3 line 57-Column 4 line 2, situation where slicing device has 1 microgrid; wherein the biological sample includes one or more biological structures selected from the group consisting of: cells, organoids, tissues, and multi-cell structures, abstract, Column 1 line 14-22, Column 2 line 32-43, Column 2 line 57-Column 3 line 19; and wherein the blade is configured to split one or more biological cells of the one or more biological structures in operation, in a fluidic configuration including two or more stages of fluidic splitters, Figure 4, Column 4 line 3-36, wherein each outlet of a fluidic splitter of a prior stage is connected to an inlet of a fluidic splitter of a subsequent stage, Figure 4, Column 4 line 3-36; wherein each fluidic splitter includes a fluidic input channel and two fluidic output channels, Column 3 line 57-Column 4 line 36, and wherein the inlet channel and the outlet channels meet at a Y-junction where the inlet channel is in fluid communication with the two outlet channels, Column 3 line 57-Column 4 line 36, Figure 4; wherein an interior tip of the Y-junction of each fluidic splitter is a blade configured to split the biological sample from the fluidic inlet channel into substantially two parts while fluid flows through the Y- junction, and to deliver the two parts separately to the two fluidic outlet channels, Column 3 line 30-33, Figure 1 and 4, Column 3 line 57-Column 4 line 36.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the BLAUCH reference with the device of SUNDSTROM so that each outlet of a fluidic splitter of a prior stage is connected to an inlet of a fluidic splitter of a subsequent stage to cleave clusters of cells into smaller cell clusters, Column 4 line 4-36.
Additional Disclosures Included is : Claim 18: wherein the method of claim 1, further comprising: encapsulating the biological sample in a droplet to facilitate self-cleaning of the blade in operation, Figure 4A-D, page 7285, left column, Supporting Information, page 1, Parallel Microfluidic Guillotine…..
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 EST.
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, LYLE ALEXANDER can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797