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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 1, 2, 9-11,13, 14, 16, 20, 22, 28, 30, 31, 33-37, 39, 40, 42, 44-46, 48, 51, 55, 60, 63-69, 73, 87, 88 and 93 are currently pending. Claims 47-49, 55 and 56 have been amended by Applicants’ amendment filed 12-02-2025. No claims have been added or cancelled by Applicant’s amendment filed 12-02-2025.
Applicant's election without traverse of Group I, claims 1, 2, 9-11,13, 14, 16, 20, 22, 28, 30, 31, 33-35 and 93, directed to a method of screening a population of variant proteins, in the reply filed on August 11, 2025 is acknowledged.
Applicant elected the species as follows:
Species (A): wherein the target molecule is a target protein or polypeptide, a target nucleic acid,…or a combination of each (claim 9);
Species (B): wherein the surface is a surface of a cell (claim 11);
Species (C): wherein the reporter element is activated within a cell, and the target molecule is immobilized on a surface of the cell (claim 20);
Species (D): wherein the signal is a fluorescent signal, an absorbance signal, a bright-field signal, or a dark field signal (claim 22); and
Species (E): wherein the contents of the microcapillary are isolated by pulsing the microcapillary with a laser (claim 31), in the reply filed on August 11, 2025 was previously acknowledged.
Claims 36, 37, 39, 40, 42, 44-46, 48, 51, 55, 60, 63-69, 73, 87 and 88 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
Claims 10, 11, 13, 14, 16, 20, 28, 34 and 93 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
The restriction requirement was deemed proper was made FINAL.
The claims will be examined insofar as they read on the elected species.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1, 2, 9, 22, 30, 31, 33 and 35 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed October 7, 2021 is a 35 U.S.C. 371 national stage filing of International Application PCT/US2020/026848, filed on April 6, 2020, which claims the benefit of US Provisional Patent Application 62/830978, filed April 8, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 2, 2025 has been considered. An initialed copy of the IDS accompanies this Office Action.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed December 2, 2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Specification Objections
The objection to the disclosure is withdrawn because it contains an embedded hyperlink and/or other form of Browser-executable code (e.g., as-filed Specification, paragraph [0278], line 4), due to Applicant’s amendment of the as-filed Specification, in the reply filed 12-02-2025.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 2, 9, 22, 30, 31, 33 and 35 is withdrawn under 35 U.S.C. 102(a1)/(a2) as being anticipated by Chen et al. (hereinafter “Chen”) (Nature Chemical Biology, 2015, 12(2), 1-9; and Supplementary Information, 2015, 12(2), 1-24) as evidenced by Baer et al. (hereinafter “Baer”) (US Patent 10526600, issued January 7, 2020; previously published as US Patent Application Publication US20160245805, published August 25, 2016).
Chen does not specifically exemplify a calcium dye assay or a T cell activation assay.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Interpretation: the term “each of the microcapillaries comprising a variant protein, an immobilized target molecule, and a reporter element” in combination with the term “wherein said reporter assay is selected from the group consisting of a calcium dye assay and a T cell activation assay, wherein each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells” in claim 1 is interpreted to refer to each microcapillary as comprising any combination of components as recited including: for a reporter assay (such as a calcium dye assay) each of the microcapillaries comprises a variant protein, an immobilized target molecule, and a reporter element; for a T cell activation assay each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells, etc.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 2, 9, 22, 30, 31, 33 and 35 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “measuring a signal from at least one reporter element in a reporter assay that indicates binding of at least one variant protein to at least one immobilized target molecule within a microcapillary of interest of the plurality of microcapillaries” such as recited in claim 1, lines 7-10 because it is unclear how there could be additional signals from additional reporter elements from the binding of additional variant proteins to additional immobilized target molecules, when claim 1, lines 3-5 recites that “each microcapillary comprises a variant protein, an immobilized target molecule, and a reporter element” (e.g., a single variant protein, a single immobilized target, and a single reporter element) and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the terms “at least one reporter element;” “at least one variant protein;” and “at least one immobilized target molecule” such as recited in claim 1, lines 7-9. There is insufficient antecedent basis for the terms “at least one reporter element;” “at least one variant protein;” and “at least one immobilized target molecule” in the claim because claim 1, lines 4-6 recite the terms a variant protein, an immobilized target molecule, and a reporter element.
Claim 1 is indefinite for the recitation of the term “each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells” such as recited in claim 1, lines 12-13 because it is completely unclear what each of the plurality of microcapillaries comprises. Instant claim 1, lines 3-5 recites that “each microcapillary comprises a variant protein, an immobilized target molecule, and a reporter element” such that it is unclear how each microcapillary comprises something different in claim 1, lines 12-13 (e.g., “each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells”). It is unclear whether the microcapillary components depend upon the assay (e.g., in T cell activation assays, microcapillaries do not comprise a reporter element, an immobilized target, or a variant protein); whether each microcapillary comprises all of the components recited (e.g., a reporter element, an immobilized target, a variant protein, and a mixture of T cells and antibody secreting cells); whether each microcapillary of the plurality comprises one or the other set of components; and/or whether each microcapillary comprises something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 2 is indefinite for the recitation of the term “each of the microcapillaries comprises an expression system” such as recited in claim 2, lines 1-2 because claim 2 depends from instant claim 1, wherein claim 1 already recites two different versions of what each of the microcapillaries comprises, such that dependent claim 2 cannot recite that each microcapillary now comprises something different. Moreover, instant claim 1 does not recite the presence of an expression system and/or anything that is expressed and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “wherein each of the variant proteins is expressed within each microcapillary via an expression system” or “wherein each…further comprises an expression system.”
Claim 2 is indefinite for the recitation of the term “the variant protein” such as recited in claim 2, line 3. There is insufficient antecedent basis for the term “the variant protein” in the claim because claim 1, line 8 recites the term “at least one variant protein.”
Claim 30 is indefinite for the recitation of the term “isolating contents of the microcapillary of interest” such as recited in claim 30, lines 1-2 because claim 30 depends from instant claim 1, wherein claim 1 does not recite specific ‘contents’ of the microcapillary of interest, such that it is unclear what is isolated (e.g., a signal, cells, two or more reporter elements, target molecules, variant proteins, bound molecules, immobilized targets, etc.) and, thus, the metes and bounds of the claim cannot be determined.
Claim 33 is indefinite for the recitation of the term “a water-glass interface between a wall of the microcapillary of interest and the contents” such as recited in claim 33, lines 1-2 because claim 33 depends from claims 1, 30 and 31, wherein claims 1, 30 and 31 do not recite that the microcapillary of interest comprises water, glass, a water-glass interface and/or a wall of a microcapillary of interest and, thus, the metes and bounds of the claim cannot be determined.
Claim 35 is indefinite for the recitation of the term “wherein each microcapillary of the plurality of microcapillaries does not comprise…or an electromagnetic radiation absorbent material” such as recited in claim 35, lines 1-5 because claim 35 depends from instant claims 1, 30 and 31, wherein claims 1, 30 and 31 do not recite a microparticle, bead, and/or the transmission of electromagnetic radiation and, thus, the metes and bounds of the claim cannot be determined.
Claim 35 is indefinite for the recitation of the term “the transmission of electromagnetic radiation” such as recited in claim 35, lines 2-3. There is insufficient antecedent basis for the term “the transmission of electromagnetic radiation” in the claim.
Claims 9, 22 and 31 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claims 2, 33 and 35 is maintained under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites (in part): “wherein each of the plurality of microcapillaries comprises an expression system, and wherein the expression system is configured to express the variant protein” in lines 1-2 because claim 2 depends from claim 1, wherein claim 1 already recites what each microcapillary comprises (e.g., a variant protein, an immobilized target molecule, a reporter element, a mixture of T cells, and antibody secreting cells). Moreover, instant claim 1 does not recite the presence of an expression system and/or anything that is expressed. Thus, claim 2 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 33 recites (in part): “wherein the laser is directed at a water-glass interface between a wall of the microcapillary of interest and the contents” in lines 1-3 because claim 33 depends from claims 1, 30 and 31, wherein claims 1, 30 and 31 do not recite water, glass, a water-glass interface, and/or a microcapillary wall. Thus, claim 33 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 35 recites (in part): “wherein each microcapillary of the plurality of microcapillaries does not comprise…electromagnetic radiation absorbent material” in lines 1-5 because claim 35 depends from claims 1, 30 and 31, wherein claims 1, 30 and 31, do not recite that each microcapillary comprises a microparticle, bead, and/or the transmission of electromagnetic radiation. Thus, claim 35 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Double Patenting
The provisional rejection of claims 1, 2, 9, 22, 30, 31, 33 and 35 is maintained on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1 – 34 of US Patent Application 18/640,571; and
Claims 25 – 38 of US Patent Application 19/006993 in view of Lim (ACS Chemical Biology, 2017, 12, 336-341) for the reasons of record.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims recited in the instant application US17/602254 including providing a microcapillary array, measuring a signal from at least one reporter element in a reporter assay, read on the steps as recited in the copending claims of application US18/640571 and US19/006993.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 1, 2, 9, 22, 30, 31, 33 and 35 is maintained on ground of nonstatutory double patenting as being unpatentable over:
Claims 1-25of U.S. Patent No. 10227583;
Claims 1-28 of U.S. Patent No. 11085039; and
Claims 1-26 of U.S. Patent No. 11473081, for the reasons of record.
Although the claims at issue are not identical, they are not patentably distinct from each other because: the instant claims, and the claims of U.S. Patent Nos. 10227583, 11085039 and 11473081 teach screening a population of variant proteins using a microcapillary array, wherein the variant protein associates with the immobilized target molecule in the microcapillary with a particular affinity.
New Objections/Rejections
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 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.
(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.
Claims 1, 2, 9, 22, 30, 31, 33 and 35 are rejected under 35 U.S.C. 102(a1)/(a2) as being anticipated by Fitzgerald et al. (hereinafter “Fitzgerald”) (Analytical Chemistry, 2015, 87, 997-1003)
Regarding claims 1, 2, 9, 22 and 35, Fitzgerald teaches in Figure 1 a schematic of DiCAST process, such that during the DiCAST process, single cells are captured in densely packed microcapillary arrays (A) and sealed reversibly to precoated assay surfaces to detect antibodies of interest (B), wherein cells which produce an antigen-specific antibody will be represented on the assay surface as a fluorescent spot when imaged, which can then be related back to the exact capillary containing the desired cell, such that a high resolution image of a fluorescent assay is generated and subjected to image analysis and processing (interpreted as a microcapillary array comprising an immobilized target molecule, a variant protein, and a reporter element; target protein; interpreting capturing as binding; and generating a fluorescent signal, claims 1, 9 and 22) (pg. 998, Figure 1). Figure 1 is shown below:
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Fitzgerald teaches the immunization of mice and preparation of cells for hybridoma and direct B cell experiments, wherein cells are extracted from the spleen of the immunized animal into sterile media, washed once with media, and brought forward for either hybridoma fusion or direct analysis on DiCAST (interpreted as a plurality of microcapillaries comprising a mixture of T cells and ASCs; and does not comprise microparticles, claims 1 and 35) (pg. 998, col 2, last partial paragraph, Title, and lines 9-12). Fitzgerald teaches a microcapillary array assay, wherein PDMS was coated with antigen in PBS and incubated; the cells to be screened were diluted to the required level, in appropriate media, and loaded on to a 40 μm array, and the array was sealed to the prepared PDMS, wherein the cell number loaded to the array is on the basis of limiting dilution and follows a Poisson distribution; and that after incubation, the array was carefully removed and the PDMS surface was washed gently with PBS; a secondary detection agent (various) was added to the surface and incubated for 1 h at room temperature; the surface was then washed, dried, and scanned using a PerkinElmer GxArray scanner with a 533 nm (Cy3) or 633 nm laser (Cy5) (interpreting immunized cells as an expression system; providing a microcapillary array; cells; interpreting antigen coating as an immobilized target molecule; and measuring a signal from at least one report element, claims 1 and 2) (pg. 998, col 1, last partial paragraph, Title; and pg. 998, col 2; first partial paragraph, lines 3-7 and 11-17).
Regarding claims 30 and 31, Fitzgerald teaches that the single capillary of interest is automatically located using the software, and the contents of the capillary are recovered by ablating a hole in the sealant to allow a flow of nitrogen to simply blow the contents into a well of a 384 well plate positioned below the capillary array (interpreted as isolating the contents of the microcapillary of interest; ablation carried out by pulsing with a laser, claim 30) (pg. 998, col 1, first partial paragraph, lines 27-31). Fitzgerald teaches scanning using a PerkinElmer GxArray scanner with a 533 nm (Cy3) or 633 nm laser (Cy5) (interpreted as laser scanning as pulsing with a laser, claim 30) (pg. 998, col 2, first partial paragraph, lines 15-17).
Fitzgerald does not specifically exemplify a laser directed at the water-glass interface of the microcapillary of interest (claim 33).
Fitzgerald meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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.
Claims 1, 2, 9, 22, 30, 31, 33 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Cochran et al. (hereinafter “Cochran”) (US Patent No. 10370653, issued August 6, 2019; US Patent Application Publication 20160244749, published August 25, 2016) in view of Ricicova et. al. (hereinafter “Ricicova”) (US Patent No. 10725024, issued July 28, 2020; US20160252495, published September 1, 2016). This is a new rejection necessitated by amendment of the claims in the response filed 12-02-2025.
Regarding claim 1, Cochran teaches that the disclosure is directed to a method for screening a library of cells having a plurality of genotypes for a cell having a phenotype of interest for producing a molecule of interest, wherein the method includes loading a microcavity array with the library of cells; incubating the array under conditions that allow for production of the molecule of interest; imaging the array to identify a cavity comprising cells having the phenotype of interest; and extracting the contents of the cavity comprising cells having the phenotype of interest by directing electromagnetic radiation from a pulsed diode laser at a radiation absorbing material associated with the cavity (interpreted as providing a microcavity array; comprising cells; and isolating the contents of the microcavity by pulsing a laser, claims 1, 30 and 31) (col 2, lines 8-19). Cochran teaches that the cells can be expanded in the array and can be selected from mammalian cells, yeast cells, and bacterial cells (interpreting mammalian cells as encompassing a mixture of T cells and antibody-secreting cells, claim 1) (col 2, lines 24-26). Cochran teaches that Figures 3A and 3B show an embodiment of a microcapillary array associated with a transparent glass transfer plate with a conductive coating (interpreted as a microcapillary array, claim 1) (col 3, lines 29-31; and Figures 3A-B). Cochran teaches that the method includes creating a library of cells producing a mutant form of a fluorescent protein; and screening the library for cells having the property of interest, wherein the screening method includes loading a microcavity array with the library of cells; incubating the array under conditions that allow for production of the mutant form; imaging the array to identify a cavity comprising cells producing the mutant form; and extracting the contents of the cavity comprising cells producing the mutant form (interpreted as providing a microcavity array comprising a mixture of cells; cavity producing the mutant form is a capillary of interest; producing a protein variant; and measuring a signal, claim 1) (col 2, lines 54-63). Cochran teaches that the methods of the disclosure include identifying and isolating of biological cells, including, but not limited to, cell lines that express or produce proteins, carbohydrates, enzymes, peptides, hormones, receptors; other cell lines that produce antibodies; genetically engineered cells; and activated cells (interpreted as encompassing a mixture of T cells and antibody-secreting cells; and interpreting proteins, peptides, carbohydrates, etc. as target molecules, claims 1 and 9) (col 5, lines 47-51). Cochran teaches that microarrays can be manufactured by bundling millions or billions of cavities or pores, such as in the form of silica capillaries, and fusing them together (interpreted as microcapillaries, claim 1) (col 7, lines 10-13). Cochran teaches that the capillary walls of the array are comprised of multiple layers, wherein one or more layers of the walls are made of a low refractive index material that prevents or substantially diminishes transmission of electromagnetic radiation between cavities of the array (interpreted as comprising walls; and does not comprise microparticles capable of inhibiting EM radiation, claims 1 and 35) (col 7, lines 24-28). Cochran teaches that the concentration of the suspension of heterogeneous population of cells and the dimensions of the array are arranged such that 1-1000 biological elements, distributed into at least one of the microcavities of the array (interpreting the microcapillaries to comprise a mixture of cells, target molecules, and variant proteins, claim 1) (col 10, lines 48-55). Cochran teaches that the method can comprise identifying new therapeutic drugs, wherein a drug binding partner known to be involved in a disease condition (e.g., for example, an antibody, a biological receptor and/or enzyme) can be screened against a plurality of cells secreting or surface-displaying various compounds suspected of having affinity for the binding partner, such that the microcavities containing the cells displaying or secreting compounds having the highest binding affinity can be identified with an appropriate reporter system (interpreted as a reporter assay comprising a reporter, and a mixture of cells displaying of secreting antibodies include T cells and antibody secreting cells; and binding a target molecule, claim 1) (col 23, lines 60-67). Cochran teaches that the apparatus includes a detector that receives electromagnetic (EM) radiation from the labels in the sample array, wherein the detector can identify at least one cavity (e.g., a microcavity) emitting electromagnetic radiation from one or more labels (interpreted as measuring a signal from a reporter assay including within a microcapillary of interest, claim 1) (col 22, lines 1-5). Cochran teaches a method for measuring enzyme kinetics for a member of a protein enzyme library produced by a library of cells having a plurality of genotypes for producing mutant forms of a protein enzyme, comprising loading a microcavity array with the library of cells and incubating the array in the presence of a substrate for the protein enzyme under conditions that allow for production of the enzyme of interest, wherein the array can be imaged at selected intervals to provide a time resolved analysis of enzyme activity (interpreted as microcapillaries comprising a mixture of cells, a variant protein, a reporter element; and measuring a signal indicating binding, claim 1) (col 25, lines 35-46). Cochran teaches that the biological cell produces and/or expresses a fluorescent protein, or produces a protein fused to a fluorescent protein such as GFP (interpreted as variant proteins; target molecule immobilized on the surface of the cell; and measuring a signal, claim 1) (col 24, lines 52-55). Cochran teaches capture binding partners and detection binding partner pairs, e.g., capture and detection antibody pairs, can be used such as in a heterogeneous assay protocol in which, typically, two binding partners, e.g., two antibodies, are used, wherein one binding partner is a capture partner, usually immobilized on a particle, and the other binding partner is a detection binding partner, typically with a detectable label attached (interpreted as a target molecule immobilized on a particle, claim 1) (col 30, lines 7-13).
Regarding claim 2, Cochran teaches that the biological cell produces and/or expresses a fluorescent protein, or produces a protein fused to a fluorescent protein such as GFP (interpreted as an expression system configured to express a variant protein, claim 2) (col 24, lines 52-55).
Regarding claim 9, Cochran teaches that a plurality of cells secreting or surface-displaying various proteins and/or peptides suspected of having affinity for binding partners known to be involved in a disease condition (i.e., for example, a protein and/or peptide) can be screened against the binding partners (interpreting cells secreting or surface-displaying various proteins as a mixture of T-cells and antibody secreting cells; and interpreting proteins and peptides as immobilized target molecules, claim 9) (col 24, lines 23-28).
Regarding claim 22, Cochran teaches that Figure 8 panel (a) shows histograms of the fluorescence intensity in microcavities in the presence or absence of magnetic beads; and panel (b) shows the fluorescence and bright-field images of the two conditions (interpreted as a fluorescent or bright-field signal, claim 22) (col 3, lines 44-47; and Figure 8).
Regarding claims 30 and 31, Cochran teaches extracting the contents of the cavity comprising cells having the phenotype of interest by directing electromagnetic radiation from a pulsed diode laser at a radiation absorbing material associated with the cavity (interpreted as providing a microcavity array; comprising cells; and isolating the contents of the microcavity by pulsing a laser, claims 1, 30 and 31) (col 2, lines 15-19).
Regarding claim 33, Cochran teaches that Figures 4 and 5 show an example process of extraction of the contents from cavities of microcavity arrays using a laser focused on, and delivering electromagnetic radiation to, the interface between the sample and the wall of the microcavity (interpreted as the laser directed to the water-glass interface, claim 33) (col 3, lines 32-36; and Figures 4 & 5).
Regarding claim 35, Cochran teaches that the sidewalls of the cavities of the arrays are not transmissive to electromagnetic radiation, or the cavities are coated with a material that prevents the transmission of electromagnetic radiation between cavities of the arrays; and that the capillary walls of the array are comprised of multiple layers, wherein one or more layers of the walls are made of a low refractive index material that prevents or substantially diminishes transmission of electromagnetic radiation between cavities of the array (interpreted as comprising walls; and does not comprise microparticles capable of inhibiting EM radiation, claims 1 and 35) (col 8, lines 17-21 and 24-28).
Cochran does not specifically use the term T cell (claim 1, in part).
Regarding claim 1 (in part), Ricicova teaches that the method comprises, retaining a plurality of individual cell populations in separate microfluidic chambers, wherein at least one of the individual cell populations comprises one or more effector cells and the contents of the separate microfluidic chambers further comprise a readout particle population comprising one or more readout particles, incubating the individual cell populations and the readout particle population within the microfluidic chambers, assay the individual cell populations for the presence of the extracellular effect, wherein the readout particle population or subpopulation thereof provides a readout of the extracellular effect (interpreted as a mixture of T cells and ASCs, claim 1) (col 4, lines 17-28). Ricicova teaches that once the cell populations are incubated and assayed, the method comprises identifying, based on the results of the assay, a cell population from amongst the plurality that exhibits a variation in the extracellular effect, as compared to one or more of the remaining cell populations of the plurality, wherein the one or more effector cells comprise an antibody secreting cell; and/or the one or more effector cells comprise a plasma cell, B cell, plasma blast, a cell generated through the expansion of memory B cell, a hybridoma cell, a T cell, CD8+ T cell, and CD4+ T cell, a recombinant cell engineered to produce antibodies, a recombinant cell engineered to express a T cell receptor, or a combination thereof (interpreted as a mixture of T cells and ASCs, claim 1) (col 4, lines 28-40). Ricicova teaches that the effector cell is a cell that secretes or displays a protein, wherein other cell types that qualify as effector cells include T cells (e.g., CD8+ T cell, and CD4+ T cell), hematopoietic cells, cell lines derived from humans and animals, recombinant cell lines, e.g., a recombinant cell line engineered to produce antibodies, a recombinant cell line engineered to express a T cell receptor (interpreted as a mixture of T cells and ASCs, claim 1) (col 27, lines 1-2 and 20-25). Ricicova teaches that a readout particle population is a heterogeneous population of readout cells and comprises readout cells engineered to express a cDNA library, whereby the cDNA library encodes for cell surface proteins, wherein the readout particle population is fluorescently labeled and a change in fluorescence is correlated with the presence and/or size of the extracellular effect (col 44, lines 64-67; and col 58, lines 20-23). Ricicova teaches retaining, in each of a plurality of microreactors, one of a plurality of heterogeneous cell populations, each population comprising 10 to 500 cells, wherein each heterogeneous cell population comprises one or more ASCs, wherein the contents of each microreactor further comprise a readout particle population comprising one or more readout beads, readout cells, or a combination thereof displaying the target epitope on their surfaces, and wherein individual heterogenous cell populations are retained in individual microreactors (interpreted as a mixture of T cells and ASCs, claim 1) (col 185, lines 44-53).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of assaying a cell population for the presence of an extracellular effect as exemplified by Ricicova, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method for the high-throughput analysis of cells and protein products, and the laser-extraction of microcavity contents as disclosed by Cochran to include the method of retaining and assaying heterogenous populations of cells in separate chambers including effector cells such as T cells and ASCs as taught by Ricicova with a reasonable expectation of success in the high-throughput screening of libraries of cells having a phenotype of interest for producing a molecule or interest; and/or in identifying cell populations comprising an effector cell having an extracellular effect.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 1, 2, 9, 22, 30, 31, 33 and 35 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684