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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on May 29, 2026 has been entered.
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, 9-11, 16, 20, 22, 28, 34-37, 39, 40, 42, 44-46, 48, 51, 55, 60, 63-69, 73, 87, 88 and 93 are currently pending. Claims 1, 11, 34, 35 and 93 have been amended by Applicants’ amendment filed 05-29-2026. Claims 2, 13, 14, 30, 31 and 33 have been canceled by Applicants’ amendment filed 05-29-2026. No claims have been added by Applicants’ amendment filed 05-29-2026.
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, and the election of 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.
Please Note: instant claim 34 has been amended to depend from claim 1. In the reply filed August 11, 2025, Applicant elected for Species (E), wherein the contents of the microcapillary are isolated by pulsing the microcapillary with a laser (claim 31). Instant claim 34 recites that the contents of the microcapillary are isolated using a two-stage sample recovery element. Therefore, amended claim 34 remains withdrawn as being directed to a non-elected species.
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 and was made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 9, 22 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.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed May 29, 2026 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.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 9, 22 and 35 is withdrawn under 35 U.S.C. 102(a1)/(a2) as being anticipated by Fitzgerald et al. (hereinafter “Fitzgerald”) (Analytical Chemistry, 2015, 87, 997-1003).
Fitzgerald does not specifically exemplify pulsing a laser at a fluid-glass interface of the microcapillary of interest.
In view of the withdrawn rejection, Applicant’s argument is rendered moot.
Maintained Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 9, 22 and 35 are 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 “wherein each of the plurality of microcapillaries comprising…configured to secrete the variant protein” such as recited in claim 1, lines 3-8 because the claim fails to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 1 appears to recite that each of the plurality of microcapillaries comprises two different compositions, such that it is completely unclear what each of the plurality of microcapillaries actually comprises. For example, claim 1 recites that each of the plurality of microcapillaries comprises: (1) a variant protein, an immobilized target molecule, and a reporter element; and (2) a mixture of T cells and antibody secreting cells. As an initial matter, the as-filed Specification and original claims do not teach or recite that each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells. Thus, it is unclear whether each of the plurality of microcapillaries comprises a mixture of (1) and (2); comprises (1) or (2); whether a T cell are intended to be represented an immobilized target molecule, and the antibody secreting cells are intended to be represented by a variant protein; and/or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “said reporter assay is…consisting of a calcium dye assay and T cell activation assay” such as recited in claim 1, lines 12-13 because measuring the binding of a variant protein to an immobilized target molecule appears to refer to a protein binding assay, and not to a calcium dye assay and/or to a T cell activation assay. A calcium dye assay measures intracellular calcium concentration changes, requiring live cell fluorescence imaging as evidenced by Cai (Abstract; and pg. 1, col 2, last partial paragraph); while a T cell activation assay requires T cells, and measuring a response to a stimuli including specific antigens as evidenced by ICE Biosciences (pg. 2, entire page), wherein the presence of calcium ions, T cells and/or a stimulation reagent within each microcapillary is not supported in the as-filed Specification and/or the original claims, such that it is completely unclear how either assay can be conducted in the microcapillaries as recited in claim 1 and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “fluid-glass interface” such as recited in claim 1, lines 15-16 because instant claim 1 does not recite the presence of a fluid (e.g., solvent, buffer, etc.). Moreover, when a microcapillary merely comprises a variant protein bound to an immobilized target molecule, it is unclear that a laser pulse directed to the microcapillary as recited will produce a vapor force expansion to isolate any contents, and, thus, the metes and bounds of the claim cannot be determined.
Claim 9 is indefinite for the recitation of the term “a combination of each” such as recited in claim 9, lines 2-3 because claim 9 depends from instant claim 1, wherein claim 1, lines 5-6 recites the term “an immobilized target molecule”, such that claim 1 does not recite that each microcapillary comprises a plurality of immobilized target molecules 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 any or all of a microparticle capable of inhibiting transmission of…radiation absorbent material” such as recited in claim 35, lines 1-5 because claim 35 depends from instant claim 1, wherein claim 1 does not recite the presence of microparticles, electromagnetic radiation, electromagnetic radiation absorbent magnetic microparticle, magnetic beads, electromagnetic radiation absorbent materials, etc. and, thus, the metes and bounds of the claim cannot be determined.
Claim 22 is indefinite insofar as it ultimately depends from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 35 is maintained, and claim 9 is newly rejected, 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 9 recites (in part): “wherein the immobilized target molecule is a target protein or polypeptide, a target nucleic acid, a target carbohydrate, or a combination of each” in lines 1-3 because claim 9 depends from instant claim 1, wherein claim 1, lines 5-6 recite the term “an immobilized target molecule”, such that claim 1 does not recite that each microcapillary comprises a plurality of immobilized target molecules. Thus, claim 9 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 any or all of…electromagnetic radiation absorbent material” in lines 1-5 because claim 35 depends from claim 1, wherein claim 1, does not recite that each microcapillary comprises microparticles, electromagnetic radiation, electromagnetic radiation absorbent magnetic microparticle, magnetic beads, electromagnetic radiation absorbent materials, etc. 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.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 9, 22 and 35 is maintained 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).
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, claim 1) (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). 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 a reporter element, claim 1) (col 24, lines 52-55). 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, claim 1) (col 2, lines 15-19). 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 1) (col 3, lines 32-36; and Figures 4 & 5). Cochran teaches that the electromagnetic radiation is focused on the electromagnetic radiation absorbing material, resulting in linear absorption of the laser energy and cavitation of the liquid sample at the material/liquid interface, wherein the electromagnetic radiation causes an intense localized heating of an electromagnetic radiation absorbing material of the array causing explosive vaporization and expansion of a thin layer of fluid in contact with the material without heating the remainder of the contents of the cavity (interpreted as vapor force expansion, claim 1) (col 17, lines 3-11). Cochran teaches that the cavities of interest are selected and then extracted by focusing a 349 nm solid state UV laser at 20-30% intensity power, such that the source is a frequency tripled, pulsed solid-state Nd:YAG or Nd:YVO4 laser source emitting about 1 micro-Joule to about 1 milli-Joule pulses in about a 50 nanosecond pulse, wherein the source is a diode-pumped Q-switched Nd:YLF Triton UV 349 nm laser (Spectra-Physics) (interpreted as laser pulses, claim 1) (col 17, lines 63-67; and col 18, lines 1-4).
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 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 methods for the high-throughput analysis of cells and protein products; as well as, the extraction of microcavity contents using laser pulses 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.
Response to Arguments
Applicant’s arguments filed May 29, 2026 have been fully considered and are not found persuasive. Applicants essentially assert that: (a) Cochran teaches usage of beads or black glass microcapillary walls for isolating contents of microcapillaries, not pulsing a laser at a fluid-glass interface between the wall of the microcapillary of interest and the contents of the microcapillary of interest to cause vapor force expansion, wherein Figures 4 and 5 do not specifically discuss how samples were extracted (Applicant Remarks, pg. 11 through pg. 12, Claim 1); (b) Figure 7 does not examine a condition where there are no beads included. As bead concentration decreases, the extraction efficiency sharply drops. Alone, Figure 7 would dissuade one of skill in the art to exclude beads, as a skilled artisan would understand that excluding beads would lead to poor extraction efficiencies; and the present claims require directing a laser to the fluid-glass interface between the microcapillary wall and the contents, which is sufficient for sample extraction without addition of a particular radiation-absorbing material to the microcapillary (Applicant Remarks, pg. 13 through pg. 14); and (c) with regard to Figure 7, Cochran teaches that some sort of laser-absorbing material needs to be included within the microcapillary to allow for the contents of the microcapillary to be isolated by laser pulse. In contrast, the present claims require directing a laser to the fluid-glass interface between the microcapillary wall and the contents, which is sufficient for sample extraction without addition of a particular radiation absorbing material to the microcapillary (Applicant Remarks, pg. 14, last partial paragraph through pg. 15, first full paragraph)
Regarding (a), it is noted that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). As noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant’s assertion that Cochran does not teach pulsing a laser at a fluid-glass interface between the wall of the microcapillary of interest and the contents of the microcapillary of interest to cause vapor force expansion, is not found persuasive. As an initial matter, it is noted that instant claim 1 does not recite the presence of any fluid. Thus, a laser pulse directed to the microcapillaries as recited in claim 1 will not undergo vapor force expansion. Additionally, instant claim 1 does not recite any specific method of ‘isolating’ contents, such that the “extraction” taught by Cochran, which uses a pulsed diode laser directed to the same portion of the cavity, and which causes explosive vaporization and expansion of a thin layer of fluid, clearly corresponds to the method as recited in instant claim 1. The Examiner contends that the combined references of Cochran and Ricicova teach all of the limitations of the claims. To that end -
Cochran teaches:
Extracting the contents of the cavity by directing electromagnetic radiation from a pulsed diode laser (interpreted as a pulsing laser, claim 1) (col 2, lines 15-19).
That the electromagnetic radiation is focused on the electromagnetic radiation absorbing material, resulting in linear absorption of the laser energy and cavitation of the liquid sample at the material/liquid interface, causing an intense localized heating of the array; and causing explosive vaporization and expansion of a thin layer of fluid in contact with the material without heating the remainder of the contents of the cavity (interpreted as vapor force expansion, claim 1) (col 17, lines 3-11).
The cavities of interest are selected and then extracted by focusing a 349 nm solid state UV laser, such as a pulsed solid-state Nd:YAG or Nd:YVO4 laser source emitting about 1 micro-Joule to about 1 milli-Joule pulses in about a 50 nanosecond pulse (interpreted as laser pulses, claim 1) (col 17, lines 63-67; and col 18, lines 1-4).
Cochran clearly teaches pulsing a laser at the fluid-glass interface to cause vapor force expansion. Thus, the rejection is maintained.
Regarding (b), note that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Moreover, "[T]he use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. See In re Heck, 699 F.2d 1331, 1332-33,216 USPQ 1038, 1039 (Fed. Cir. 1983); In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275,277 (CCPA 1968); Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); and Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005). Additionally, MPEP 2123(II) indicates that “disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)”. Additionally, MPEP 2141.02(VI) states that "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). A reference teaches away “when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken” in the claim. Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir. 2013). A reference that “merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into” the claimed invention does not teach away. Id. Applicant’s assertion that Figure 7 does not examine a condition where there are no beads included. As bead concentration decreases, the extraction efficiency sharply drops. Alone, Figure 7 would dissuade one of skill in the art to exclude beads, as a skilled artisan would understand that excluding beads would lead to poor extraction efficiencies; and the present claims require directing a laser to the fluid-glass interface between the microcapillary wall and the contents, which is sufficient for sample extraction without addition of a particular radiation-absorbing material to the microcapillary, is not found persuasive.
Regarding that the laser is directed to the fluid-glass interface, please see the Examiner’s remarks supra.
Regarding Applicant’s assertion that Figure 7 would dissuade one of skill in the art to exclude beads, because a skilled artisan would understand that excluding beads would lead to poor extraction efficiencies, this is not found persuasive. As an initial matter, it is noted that Figure 7 represents a single embodiment in the Cochran application. Moreover, instant claim 1 uses the term “comprising”, which is open-ended and does not exclude additional, unrecited elements or method steps, including the addition of beads. Additionally, claim 1 recites that the microcapillaries comprise an immobilized target molecule, which can include immobilization of the target molecule on the surface of a bead (See; as-filed Specification, paragraph [0061]). Cochran teaches in Figure 8, the effects of fluorescence measurements in the presence and absence of magnetic beads. Additionally, Cochran also teaches:
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. 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 electro-magnetic radiation from a pulsed diode laser at a radiation absorbing material associated with the cavity (corresponding to microcapillaries that exclude beads) (col 2, lines 8-19).
Consistent with MPEP 2143.01(I), Cochran clearly does not criticize, discredit, or otherwise discourage investigation into the exclusion of beads in each of the microcapillaries, such that Cochran does not teach away from microcapillaries that exclude beads. Thus, the rejection is maintained.
Regarding (c), Applicant’s assertion that Figure 7 suggests that some sort of laser-absorbing material needs to be included within the microcapillary to allow for the contents of the microcapillary to be isolated by laser pulse. In contrast, the present claims require directing a laser to the fluid-glass interface between the microcapillary wall and the contents, which is sufficient for sample extraction without addition of a particular radiation absorbing material to the microcapillary, is not found persuasive. As an initial matter, please see the discussion supra regarding that Figure 7 merely describes a single embodiment of Cochran; as well as, that the teachings of Cochran supra, which do not include microcapillaries comprising radiation absorbing material. Moreover, instant claim 1 uses the term “comprising”, which is open-ended and does not exclude additional, unrecited elements or method steps, including radiation absorbing material. Thus, the claims remain rejected.
Double Patenting
The provisional rejection of claims 1, 9, 22 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 19/006,993 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, 9, 22 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.
Response to Arguments
Applicant’s arguments filed May 29, 2026 have been fully considered and are not found persuasive. Applicants essentially assert that: (a) Applicant requests reconsideration of the double patenting rejection in view of the amendments made herein (Applicant Remarks, pg. 16, second full paragraph).
Regarding (a), Applicant did not specifically indicate how the claims of the copending applications recited supra are patentably distinct from the instant claims as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
New Objections/Rejections
Claim Rejections - 35 USC § 112(a) – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 9, 22 and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art (hereafter the Artisan), that the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application". Claim 1 recites (in part): “each of the plurality of microcapillaries comprising a variant protein, an immobilized target molecule, a reporter element, wherein the variant protein binds to the immobilized target molecule, and wherein each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells, wherein the antibody secreting cells are configured to secrete the variant protein” in lines 3-8; and “said reporter assay is selected from the group consisting of a calcium dye assay and T cell activation assay” in lines 12-13. However, support was not found for these limitations in the as-filed Specification and/or the original claims.
Upon review of the instant as-filed Specification and original claims, support was not found for a plurality of microcapillaries, wherein each microcapillary comprises both: (1) a variant protein, an immobilized target molecule, a reporter element, wherein the variant protein binds to the immobilized target molecule; and (2) a mixture of T cells and antibody secreting cells, wherein the antibody secreting cells are configured to secrete the variant protein as recited in instant claim 1. Moreover, a calcium dye assay and/or a T cell activation assay require cells; and the instant assays are not taught as comprising a variant protein, a target molecule, and a reporter molecule in each microcapillary as recited in claim 1. The instant as-filed Specification, filed October 7, 2021 teaches, for example: “each microcapillary comprising a variant protein, an immobilized target molecule, and a reporter element” (paragraphs [0007]; [0009]; [0140], etc.); “[I]n some embodiments, each microcapillary in the microcapillary array comprises 0 to 5 variant proteins from the population of variant proteins” (paragraph [0036]); “an array comprising a plurality of microcapillaries, each microcapillary comprising a variant protein, an immobilized target molecule, and a reporter element, wherein the variant protein associates with the immobilized target molecule w-ith a particular affinity” (paragraph [0049]); “each microcapillary in the microcapillary arrays of the instant screening methods also comprises an immobilized target molecule” (paragraph [0160]); “further comprises an agent or agents to improve viability of the cellular expression system” (paragraph [0172]); “further comprises a growth additive” (paragraph [0194]); and “in some embodiments, the T cell activation assay comprises a mixture of T cells and antibody secreting cells (ASC)” (paragraph [0099]). No such corresponding teaching of each microcapillary comprising a variant protein, an immobilized target molecule, a reporter element, wherein the variant protein binds to the immobilized target molecule; and wherein each of the plurality of microcapillaries comprises a mixture of T cells and antibody secreting cells, wherein the antibody secreting cells are configured to secrete the variant protein as recited in instant claim 1 is taught by the instant as-filed Specification and/or the original claims.
A claim-by-claim analysis and for independent claim 1, and a method step by method step analysis regarding where support can be found for the composition found in each of the plurality of microcapillaries in the originally filed specification is respectfully suggested. See MPEP § 2163 particularly § 2163.06.
Claims 1, 9, 22 and 35 will remain rejected until Applicant cancels all new matter.
Conclusion
Claims 1, 9, 22 and 35 are rejected.
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).
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, Heather Calamita can be reached on (571) 272-2876. 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.
/AMY M BUNKER/Primary Examiner, Art Unit 1684
Prosecution Insights