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 .
DETAILED ACTION
Status of Claims
1. Claims 1-16 are pending and are under examination.
Priority
2. This application is a continuation of United States Patent Application Serial Number (ASN) 16/941,933 filed 07/29/2020, which is a continuation of ASN 15/517,921 filed 04/07/2017 which is a 371 National Stage application of PCT/US2015/054979 filed 10/09/2015 which claims the benefit of priority of Provisional Application Serial Number 62/061,739 filed 10/09/2014. Accordingly, the effective filing date of the instant application is October 9, 2014 which is the filing date of Provisional Application Number 62/061,739 from which the benefit of priority is claimed.
Specification
3. The disclosure is objected to because of the following informalities: In the Brief Description of the Drawings: Figures 13A and 13B have not been differentially described.
Appropriate correction is required.
Information Disclosure Statement
4. The listing of references in the specification in pages 30-31 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
5. Claims 1-16 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 pre-AIA the applicant regards as the invention.
Claim 1, part a) is indefinite in reciting “a plurality of layers in which are disposed…” because it is unclear what is encompassed in the recitation of layers and what these layers are intended to be composed of.
Claim 1, part b) is vague and indefinite in reciting “a sample fluid mixture of components to be isolated” because it is unclear what is encompassed in the recitation of “sample fluid”, “mixture”, and “components” in relation to the preamble which recites “A microfluidic chip for the detection of infection in a patient.” Does Applicant intend a sputum sample from which bacterial cells are detected for respiratory infection?
Claim 4 recites “a separation channel for monocyte depletion;” however, claim 4 is indefinite because it fails to clearly define what specific structural component is comprised or configured in the separation channel that renders it capable of monocyte depletion.
Claim 4 is further vague and indefinite in relation to claims 1 and 3 from which it depends for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. In this case, claim 4 recites “a separation channel for monocyte depletion;” however, it fails to clearly define what essential structural cooperative relationship exists between the monocytes to be depleted and the “sample fluid mixture of components to be isolated” in the microfluidic detection chip of claim 1 so as to be configured to detect infection in a patient as set forth in claim 1. Perhaps, Applicant intends “a blood sample comprising cells to be isolated that provides detection of infection in a patient.” See also claims 7-9.
Claim 7 is vague and indefinite in relation to claims 1 and 6 from which it depends for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. In this case, claim 7 recites “wherein the one or more separation channels are coated with anti-CD14” thus comprising “an affinity surface” as set forth in claim 6; however, it fails to clearly define what essential structural cooperative relationship exists between the biotinylated anti-CD14 coated on the one or more separation channels in claims 6 and 7, and the “sample fluid mixture of components to be isolated” in the microfluidic detection chip of claim 1 so as to be configured to detect infection in a patient as set forth in claim 1.
Claim 8 is vague and indefinite in relation to claims 1 and 6 from which it depends for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. In this case, claim 8 recites “wherein the one or more separation channels are coated with anti-CD19” thus comprising “an affinity surface” as set forth in claim 6; however, it fails to clearly define what essential structural cooperative relationship exists between the biotinylated anti-CD19 coated on the one or more separation channels in claims 6 and 8, and the “sample fluid mixture of components to be isolated” in the microfluidic detection chip of claim 1 so as to be configured to detect infection in a patient as set forth in claim 1.
Claim 9 is vague and indefinite in relation to claims 1 and 6 from which it depends for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. In this case, claim 9 recites “wherein the one or more separation channels are coated with anti-CD64” thus comprising “an affinity surface” as set forth in claim 6; however, it fails to clearly define what essential structural cooperative relationship exists between the biotinylated anti-CD64 coated on the one or more separation channels in claims 6 and 9, and the “sample fluid mixture of components to be isolated” in the microfluidic detection chip of claim 1 so as to be configured to detect infection in a patient as set forth in claim 1.
Claim 11 recites “wherein the second affinity surface captures resting neutrophils;” however, claim 11 is indefinite because it fails to clearly define what specific structural component is comprised or configured in the second affinity surface that renders it capable of capturing resting neutrophils.
Claim 11 is further vague and indefinite in appearing to be incomplete in reciting “wherein the second affinity surface captures resting neutrophils;” because it fails to clearly define what the first affinity surface is intended to capture.
Claim 14 is indefinite in reciting “The microfluidic chip of claim 1, further comprising enumeration of cells by cell imaging” because it appears to recite a method step in a claim set drawn to a product: a device which is specifically a microfluidic detection chip.
Claim 14 is ambiguous in relation to claim 1 from which it depends for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. In this case, claim 14 recites “The microfluidic chip … comprising enumeration of cells by cell imaging” because it fails to clearly define what essential structural cooperative relationship exists between the instant recitation of “cells” and the “sample fluid mixture of components to be isolated” in the microfluidic detection chip of claim 1 so as to be configured to detect infection in a patient as set forth in claim 1. See also claims 15 and 16.
Claim 15 is indefinite in reciting “The microfluidic chip of claim 14, … wherein the cell imaging is by flatbed scanning” because it appears to recite a method step in a claim set drawn to a product: a device which is specifically a microfluidic detection chip.
Claim 16 is also indefinite in reciting “The microfluidic chip of claim 14, … wherein the cell imaging further comprises using contrast agents” because it appears to recite a method step in a claim set drawn to a product: a device which is specifically a microfluidic detection chip.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
6. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,013,396. Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a microfluidic detection chip for the detection of infection, specifically sepsis, in a patient comprising: a plurality of microchannel layers onto which are disposed a plurality of channels comprising (i) a sample input channel; (ii) one or more separation channels having one or more three-dimensional (3D) separation zones including vertical and horizontal interfaces (posts) operatively coupled to the sample input channel to receive a sample fluid from the patient and having a first affinity surface and a second affinity surface serially and operatively arranged and configured to serially capture and deplete unwanted cells such as monocytes (i.e. first: monocyte depletion), and isolate active neutrophils and resting neutrophils (i.e. second) present in the patient sample; and (iii) one or more optical channels having optical zones coupled to the separation channels and operatively configured to enumerate the active neutrophils and resting neutrophils to detect infection or sepsis in the patient. The affinity surfaces comprise biotinylated anti-CD4 and anti-CD19 antibodies that bind and capture unwanted cells and biotinylated anti-CD64 antibodies that differentially isolate active and resting neutrophils.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
7. Claims 1-6 and 9-16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Karnik et al. (US Patent 8,986,988).
Karnik et al. disclose a microfluidic detection chip for detection of sepsis (infection) by separating WBC types or subpopulations such as neutrophils in a blood sample that provide indication of sepsis (col. 2, lines 1-42; col. 17, line 44 to col. 19, line 16; Example 8; Figure 20). The microfluidic detection chip comprises a) a plurality of layers onto which a plurality of channels (flow chambers) are disposed; b) a sample input channel (inlet) into which a blood cell sample mixture is dispensed; c) one or more separation channels (separation chambers) having three-dimensional (3D) separation zones (patterned ordered layer); and d) one or more channels having one or more optical zones (col. 2, lines 1-42; col. 7, lines 34-46; col. 17, line 44 to col. 18, line 29; col. 18, lines 52-64; col. 36, lines 19-28; Example 8; Figure 3). The one or more separation channels are shown to be arranged in a series or in parallel (collection channels, sequential channels) (col. 18, lines 50-51; Figure 17; Figure 20). The one or more separation channels comprise three-dimensional (3D) separation zones which comprise at least one of a vertical interface and a horizontal interface in the form of wells, surface depressions, spherical or cylindrical edges, periodic bumps, or surface waves (col. 13, lines 15-20; col. 17, lines 22-28). The one or more separation channels of the microfluidic detection chip comprise a first affinity surface and a second affinity surface (adhesive patch) for binding to cell surface antigens of neutrophils such as anti-CD64 antibodies. The first affinity surface captures active CD64+ neutrophils and the second affinity surface captures resting CD64- neutrophils (col. 5, lines 52-64; col. 10, lines 31-50; Example 8; Example 9; Figure 20). Karnik et al. teach that the microfluidic detection chip is configured for cell enumeration by labeling them with contrast agents (colored fluid, dyes) and cell imaging via flatbed scanning (Andor 885 camera imaging) (col. 18, lines 52-64; col. 36, lines 19-28). The active and resting neutrophils are also counted and enumerated using high-contrast bright field microscopy or fluorescence scanning (fluorescence imaging) (Examples 8-10). The one or more separation channels of the microfluidic detection chip may comprise a separation channel for monocyte depletion (claims 48 and 63). According to Karnik et al., expression of CD64 in neutrophils provides a highly specific biomarker for neonatal sepsis as well as late-onset nosocomial infection (col. 34, lines 22-33)
8. Claims 1, 3-6, and 10-16 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Toner et al (US Patent 8,304,230).
Toner et al. disclose a microfluidic detection chip for detection of infection and/or medical diagnostics by separating and analyzing white blood cell (WBC) types or subpopulations in blood sample of a subject that provide indication of infection. The microfluidic detection chip comprises a) a plurality of monolayers onto which a plurality of separation channels are disposed; b) a sample input channel into which a cell sample mixture is dispensed; c) one or more (set) separation channels; and d) one or more channels having one or more optical zones (optical scanner) for visual observation of the specific selected WBC subpopulation in the blood sample of the subject that provides indication of infection (Abstract; col. 2, lines 54 to col. 3, line 7; col. 5, lines 32-44; col. 6, lines 25-33; col. 7, lines 63-66; col. 9, lines 16-23; col. 10, lines 23-24; col. 11, lines 8-29; col. 15, lines 47-48; col. 16, lines 32-43; col. 19, lines 57-64; Figure 1; Figure 25). The one or more separation channels comprise three-dimensional (3D) separation zones (microposts, ligand obstacles, sieves) which comprise at least one of a vertical interface and a horizontal interface (col. 2, line 57 to col. 3, line 7; col. 11, lines 8-29 & 38-56; col. 19, lines 3-5; Figure 19). The one or more separation channels are shown to be arranged in a series or in parallel (col. 7, lines 63-66; Figure 20). The one or more separation channels of the microfluidic detection chip has a first affinity surface and a second affinity surface comprising immobilized antibodies (anti-CD36) which may be biotinylated (ligand) for binding to cell surface receptors of the selected WBC type or subpopulation. The first and/or second affinity surfaces comprising immobilized antibodies or ligands are configured for positive binding selection of desired cells (enrichment) such as neutrophils (i.e. resting) for optical imaging and analysis and negative binding selection and separation of undesired cells (depletion) such as monocytes (Abstract; Figure 20; col. 2, line 57 to col. 3, line 7; col. 5, lines 32-45; Table 1; col. 7, lines 63-66; col. 10, lines 56-65; col. 11, lines 8-29; col. 16, lines 32-43; col. 19, lines 57-64; Figure 25). Toner et al. teach that the microfluidic detection chip is configured for cell enumeration by cell imaging via flatbed scanning (optical scanner) and uses contrasting agents for bright field microscopy or fluorescence imaging (col. 11, lines 8-29; col. 16, lines 32-43; col. 19, lines 57-64; claim 26).
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.
9. Claims 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Karnik et al. (US Patent 8,986,988) or Toner et al (US Patent 8,304,230) in view of Mortato et al. (pH controlled staining of CD4+ and CD19+ cells within a functionalized microfluidic channel. Biomicrofluidics 6:(044107) 1-12 (2012)).
Karnik et al. and Toner et al. are discussed supra. Karnik et al. and Toner et al. differ from the instant invention in failing to teach coating one or more separation channels with anti-CD4 or anti-CD19.
Mortato et al. disclose a microfluidic detection chip having functionalized microfluidic channels coated with anti-CD4 and anti-CD19 antibodies encapsulated into microgels immobilized into the inner surface of the microfluidic channels for use in binding, staining, and analysis of T cells and B cells, respectively, in the microchannel pf the microfluidic detection chip (Abstract; Figure 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the anti-CD4 and anti-CD19 antibodies in the teaching of Mortato into the microfluidic detection chip of Toner or Karnik because both of Toner and Karnik are generic with respect to antibody that is immobilized into their microfluidic channels for use in either depleting or enriching a desired type of WBC subpopulation by binding to their cell surface antigen so as to determine cell surface expression to indicate diagnosis of disease, and CD4 and CD19 are both cell surface antigens that are expressed by T cells and B cells, respectively, which are both subpopulations of lymphocytic WBCs. One of ordinary skill in the art would have had reasonable expectation of success in substituting the antibodies of Toner or Karnik with the anti-CD4 and anti-CD19 antibodies of Mortato because all of Toner, Karnik, and Mortato teach analogous art in using microfluidic detection chips having microchannels in capturing and detecting WBC subpopulation in blood samples for detection of disease.
10. No claims are allowed
Remarks
11. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Sethu et al. (Microfluidic Isolation of Leucocytes from Whole Blood for Phenotype and Gene Expression Analysis. Ana. Chem. 78: 5452-5461 (2006) IDS) teach a microfluidic detection chip device that uses antibodies that isolate leucocytes such as monocytes and neutrophils, and further separate them based on their differential expressions of activation markers (Abstract; Table 1; p. 5454, col. 2 to p. 5455, col. 1)
Cheng et al. (Enhancing the performance of point-of-care CD4+ T-cell counting microchip through monocyte depletion for HIV/AIDS diagnostics. Lab Chip 9(10): 1357-1364 (21 May 2009)) teach a two-stage microfluidic detection chip that is configured to deplete monocytes from whole blood sample followed by capturing and detecting CD4+ T cells (Abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/GAILENE GABEL/Primary Examiner, Art Unit 1678
August 21, 2026
Prosecution Insights