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
Pursuant to a preliminary amendment, claims 1-3, 6, 8, 10, 11, 14, 16, 18, 20, 21, 27-29, 32, 34, 36, 37, 40, 42, 44, 46 and 47 are currently pending in the instant application.
Response to Election/Restriction
Applicant's elected Group I without traverse, claims 1-3, 6, 8, 10, 11, 14, 16, 18, 20 and 21, drawn to a method of single cell analysis; and the election of Species as follows:
Species (A): the method of claim 1 further comprising a sequence configured to couple to the barcoded nucleic acid molecule (claim 10), in the reply filed on October 30, 2025 is acknowledged.
Claims 27-29, 32, 34, 36, 37, 40, 42, 44, 46 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 18, 20 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1-3, 6, 8, 10, 11, 14 and 16 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on July 26, 2024 and October 25, 2024 have been considered. Initialed copies of the IDSs accompany this Office Action.
Priority
The present application filed March 9, 2022 is CON of a 35 U.S.C. 371 national stage filing of
International Application No. PCT/US20/55140, filed October 9, 2020; which claims the benefit of
Provisional Patent Application 62914296, filed October 11, 2019.
Claim Objection/Rejections
Claim Interpretation: the “the partition comprises a plurality of barcoded nucleic acid molecules” recited in claim 1 are interpreted to refer to: (1) a plurality of barcoded nucleic acid molecules that are present within the intact cell; (2) a plurality of barcoded nucleic acid molecules that are present within the partition, but outside of the intact cell; and/or (3) a plurality of barcoded nucleic acid molecules that are present within the partition including those that have been released from a lysed cell.
The term “configured to” in claims 3, 6, 8, 10, 11 and 14 is interpreted to refer to an ability of a specific component to comprise or perform a recited limitation. For example, a barcode “configured to” couple to another molecule may or may not be bound to the other molecule. The barcode simply has the design and/or ability to perform the recited function (e.g., bind, identify, etc.).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, 8, 10, 11, 14 and 16 are rejected 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 “a cell” such as recited in claim 1, lines 2, 3 and 5. There is insufficient antecedent basis for the term “a cell” in the claim because claim 1, line 1 recites the term “single cell”.
Claims 1 and 3 are indefinite for the recitation of the term “the cell” such as recited in claim 1, line 5. There is insufficient antecedent basis for the term “the cell” in the claim because claim 1, line 3 recites the term “a labelled cell”.
Claim 1 is indefinite for the recitation of the terms “the barcoded nucleic acid molecule comprises the reporter sequence or a complement thereof and a partition barcode sequence or a complement thereof” such as recited in claim 1, lines 11-12 because it is unclear what the barcoded nucleic acid molecules actually comprise given that claim 1, line 8 recites that the plurality of barcoded nucleic acid molecules “comprise a plurality of partition barcode sequences”. Thus, it is unclear whether the barcoded nucleic acid molecules comprise “a plurality of partition barcodes sequences”, or whether the barcoded nucleic acid molecules comprise “the reporter sequence or a complement thereof and a partition barcode sequence or a complement thereof” and, thus, the metes and bounds of the claim cannot be determined.
Claim 3 is indefinite for the recitation of the term “cell surface molecule” such as recited in claim 3, lines 2 and 3. There is insufficient antecedent basis for the term “cell surface molecule” in the claim because claim 3 depends from claim 1, wherein claim 1 does not recite the presence of a “cell surface molecule”.
Claims 3, 11 and 14 are indefinite for the recitation of the term “optionally” such as recited in claim 3, line 3 because MPEP 2173.05(h) allows for a list of alternative limitations. However, in the instant case, the “optional” limitations are not alternative limitations, but instead they are recited as potential or possible limitations. Thus, it is unclear whether the recited component or the recited process step is actually present and/or carried out in the claim. Moreover, claim 3 recites an optional cell surface molecule that is a cell surface protein, wherein claim 1 does not recite the presence of a cell surface molecule (or a “second reporter nucleic molecule” as recited in claim 14) and, thus, the metes and bounds of the claim cannot be determined.
Claim 14 is indefinite for the recitation of the term “the second reporter nucleic molecule” such as recited in claim 14, line 3. There is insufficient antecedent basis for the term “the second reporter nucleic molecule” in the claim because claim 11, line 5 recites the term “a second reporter nucleic acid molecule”. Moreover, claim 14 depends from claims 1, 3 and 11, wherein none of claims 1, 3 and 11 recite the presence of a “second reporter nucleic molecule”.
Claim 16 is indefinite for the recitation of the term “step (c)” in claim 16, line 1 because there is insufficient antecedent basis for the term “step (c)” in the claim. Instant claim 16 depends from claims 1, 3, 11 and 14, wherein claims 1, 3, 11 and 14 do not recite a “step” (c) and, thus, the metes and bounds of the claim cannot be determined.
Claim 16 is indefinite for the recitation of the term “generating a second barcoded nucleic acid molecule from the second barcode nucleic acid molecule and the second report nucleic acid molecule” because it is unclear and confusing how a “second barcoded nucleic acid molecule” is generated using (in part) “the second barcode nucleic acid molecule” that has not yet been generated. Moreover, claim 14 recites that the “second barcode nucleic acid molecule” comprises a second sequence, such that it appears that the “second barcoded nucleic acid molecule” is already “generated” and, thus, the metes and bounds of the claim cannot be determined.
Claims 2, 6, 8 and 10 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3, 14 and 16 are 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 3 recites (in part): “wherein the capture agent is configured to couple to a cell surface molecule” in lines 1-2 because claims 3 depends from claim 1, wherein claim 1 does not recite a cell surface molecule. Thus, claim 3 is an improper dependent claim 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 14 recites (in part): “wherein the second reporter nucleic molecule further comprises a second sequence configured to couple to the second barcode nucleic acid molecule of the plurality of barcode nucleic acid molecules” in lines 3-5, wherein claim 14 depends from claims 1, 3 and 11, such that claims 1, 3 and 11 do not recite the presence of a “second reporter nucleic molecules”. Thus, claim 14 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 16 recites (in part): “wherein step (c) further comprises generating a second barcoded nucleic acid molecule” in lines 1-2 because claims 16 depends from claims 1, 3, 11 and 14, wherein claims 1, 3, 11 and 14 do not recite a “step (c)”. Thus, claim 16 is an improper dependent claim 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
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 1-3, 6, 8, 10, 11, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Mikkelsen et al. (hereinafter “Mikkelsen”) (US Patent Application Publication No. 20180105808, published April 19, 2018) in view of Fandl et. al. (hereinafter “Fandl”) (US Patent No. 10261093, issued April 16, 2019; US20160033530, published February 4, 2016).
Regarding claims 1-3, Mikkelsen teaches methods, compositions and systems for analyzing individual cells or cell populations through a partitioned analysis of contents of individual cells or cell populations, such as cancer cells and cells of the immune system, wherein the individual cells or cell populations can be co-partitioned with processing reagents for accessing cellular contents, and for uniquely identifying the content of a given cell or cell population, and subsequently analyzing the content of the cell and characterizing it as having derived from an individual cell or cell population, including analysis and characterization of nucleic acids from the cell through sequencing (Abstract). Mikkelsen teaches that a wide range of different cell surface features, e.g., cell surface proteins like cluster of differentiation or CD proteins, have significant diagnostic relevance in characterization of diseases like cancer (interpreting as CD proteins as cell surface proteins, claims 3 and 6) (paragraph [0193], lines 12-14). Mikkelsen teaches that the methods and systems described herein can be used to characterize cell features, such as cell surface features, e.g., proteins, receptors, etc., wherein the methods described herein can be used to attach reporter molecules to these cell features, that when partitioned as described above, can be barcoded and analyzed, e.g., using DNA sequencing technologies, to ascertain the presence, relative abundance and/or quantity of such cell features within an individual cell or population of cells (interpreted as a complex coupled to the surface of a cell; and the complex comprising a reporter sequence corresponding to a reporter agent; a barcode; interpreting proteins as a secreted analyte; a capture agent; partitioning, claim 1) (paragraph [0194]). Mikkelsen teaches a library of potential cell binding ligands, e.g., antibodies, antibody fragments, cell surface receptor binding molecules, or the like, provided associated with a first set of nucleic acid reporter molecules, e.g. (interpreted as a plurality of partition reporter sequence/barcodes), where a different reporter oligonucleotide sequence is associated with a specific ligand (interpreted as a capture agent), and therefore capable of binding to a specific cell surface feature (complex bound to the cell surface), such that different members of the library can be characterized by the presence of a different oligonucleotide sequence label, e.g., an antibody to a first type of cell surface protein or receptor can have associated with it a first known reporter oligonucleotide sequence, while an antibody to a second receptor protein can have a different known reporter oligonucleotide sequence associated with it (interpreted as a cell surface protein comprising a reporter; and barcoded nucleic acid molecules); and that prior to co-partitioning, the cells can be incubated with the library of ligands, that can represent antibodies to a broad panel of different cell surface features, e.g., receptors, proteins, etc. (interpreted as secreted analytes), and which include their associated reporter oligonucleotides, where unbound ligands are washed from the cells, and the cells are then co-partitioned along with the barcode oligonucleotides as describe supra, such that the partitions will include the cell or cells; as well as, the bound ligands and their known, associated reporter oligonucleotides (interpreting as contacting a reporter agent to provide a labelled cell; comprising a complex coupled to a cell surface including a capture agent, a secreted protein, and a reporter agent; partitioning the labelled cell in a partition; and generating a barcoded nucleic acid molecule comprising the reporter sequence and a partition barcode sequence, claims 1-3) (paragraph [0195]). Mikkelsen teaches oligonucleotides that include a barcode sequence are co-partitioned in, e.g., a droplet 302 in an emulsion, along with a sample nucleic acid 304, such that oligonucleotides 308 can be provided on a bead 306 that is co-partitioned with the sample nucleic acid 304, which oligonucleotides are releasable from the bead 306, wherein oligonucleotides 308 include barcoded sequence 312 and one or more functional sequences including 310, 314 and 316 (interpreted as a plurality of partition barcode nucleic acid sequences, claim 1) (paragraph [0184], lines 1-8; and Figure 3). Mikkelsen teaches that in Figure 5, a population of cells, represented by cells 502 and 504 are incubated with a library of cell surface associated reagents, e.g., antibodies, cell surface binding proteins, ligands or the like (interpreted as capture agents), where each different type of binding group includes an associated nucleic acid reporter molecule associated with it (interpreted as reporter agents), shown as ligands and associated reporter molecules 506, 508, 510 and 512 (with the reporter molecules being indicated by the differently shaded circles) (interpreting differently shaded circles as first and second reporter molecules), wherein the cell expresses the surface features that are bound by the library (interpreting expressed surface features as secreted analytes), the ligands and their associated reporter molecules can become associated or coupled with the cell surface (interpreted as a labelled cell comprising a complex; configured to couple to a cell surface), such that individual cells are then partitioned into separate partitions, e.g., droplets 514 and 516, along with their associated ligand/reporter molecules, as well as an individual barcode oligonucleotide bead as described elsewhere herein (interpreted as partitioning; and a plurality of partition barcode sequences), e.g., beads 522 and 524, respectively; wherein the barcoded oligonucleotides are released from the beads and used to attach the barcode sequence the reporter molecules present within each partition with a barcode that is common to a given partition, but which varies widely among different partitions; for example, as shown in Figure 5, the reporter molecules that associate with cell 502 in partition 514 are barcoded with barcode sequence 518, while the reporter molecules associated with cell 504 in partition 516 are barcoded with barcode 520, such that as a result, one is provided with a library of oligonucleotides that reflects the surface ligands of the cell, as reflected by the reporter molecule, but which is substantially attributable to an individual cell by virtue of a common barcode sequence, allowing a single cell level profiling of the surface characteristics of the cell, such that this process is not limited to cell surface receptors but can be used to identify the presence of a wide variety of specific cell structures, chemistries or other characteristics (interpreting differently shaded circles as first and second reporter molecules; interpreting expressed surface features bound by a library of cell binding ligands as secreted analytes; partitioning; and a plurality of partition barcode sequences, claims 1 and 11), (paragraph [0197]; and Figure 5). Figure 5 is shown below:
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Mikkelsen teaches in Figures 6 and 7, a cell is co-partitioned along with a barcode bearing bead and lysed while the barcoded oligonucleotides are released from the bead, wherein the poly-T portion of the released barcode oligonucleotide then hybridizes to the poly-A tail of the mRNA, wherein the poly-T segment then primes the reverse transcription of the mRNA to produce a cDNA transcript of the mRNA, but which includes each of the sequence segments 708-716 of the barcode oligonucleotide, such that because the oligonucleotide 702 includes an anchoring sequence 714, it will more likely hybridize to and prime reverse transcription at the sequence end of the poly-A tail of the mRNA, such that within any given partition, all of the cDNA transcripts of the individual mRNA molecules will include a common barcode sequence segment 710; and by including the unique random N-mer sequence, the transcripts made from different mRNA molecules within a given partition will vary at this unique sequence (interpreting the polyT sequence as a capture agent configured to couple a cell surface molecule; interpreting the mRNA as a secreted analyte; and barcoded nucleotides as partition barcoded sequences, barcoded nucleic acid molecules, and/or reporter agents, claim 1) (paragraph [0219]).
Regarding claims 6 and 8, Mikkelsen teaches that a sample is provided that contains cells that are to be analyzed and characterized as to their cell surface proteins (interpreted as the cell surface molecule is a cell surface protein, claim 6) (paragraph [0279], lines 4-6). Mikkelsen teaches a library of antibodies, antibody fragments, or other molecules having a binding affinity to the cell surface proteins or antigens (or other cell features) for which the cell is to be characterized (also referred to herein as cell surface feature binding groups), such that these affinity groups are referred to herein as binding groups, wherein the binding groups can include a reporter molecule that is indicative of the cell surface feature to which the binding group binds including a binding group type that is specific to one type of cell surface feature will comprise a first reporter molecule, while a binding group type that is specific to a different cell surface feature will have a different reporter molecule associated with it, wherein these reporter molecules will comprise oligonucleotide sequences (interpreting reporter molecules as reporter agents; cell surface proteins; interpreting antibodies and fragments, etc. as capture agents; and reporter agents configured to couple a secreted analyte, claims 6 and 8) (paragraph [0279], lines 7-20).
Regarding claim 10, Mikkelsen teaches that without the need for lysing the cells within the partitions, one can subject the reporter oligonucleotides to the barcoding operations described above for cellular nucleic acids, to produce barcoded, reporter oligonucleotides, where the presence of the reporter oligonucleotides can be indicative of the presence of the particular cell surface feature, and the barcode sequence will allow the attribution of the range of different cell surface features to a given individual cell or population of cells based upon the barcode sequence that was co-partitioned with that cell or population of cells, such that as a result, one can generate a cell-by-cell profile of the cell surface features within a broader population of cells (interpreted to teach a reporter agent configured to couple to a barcode nucleic acid molecule, claim 10) (paragraph [0196]).
Regarding claim 11, Mikkelsen teaches that in Figure 5, a population of cells, represented by cells 502 and 504 are incubated with a library of cell surface associated reagents, e.g., antibodies, cell surface binding proteins, ligands or the like (interpreted as capture agents), where each different type of binding group includes an associated nucleic acid reporter molecule associated with it (interpreted as reporter agents), shown as ligands and associated reporter molecules 506, 508, 510 and 512 (with the reporter molecules being indicated by the differently shaded circles) (interpreting differently shaded circles, and binding groups each comprising a reporter molecule as first reporter molecules and second reporter molecules), wherein the cell expresses the surface features that are bound by the library (interpreting expressed surface features as secreted analytes), the ligands and their associated reporter molecules can become associated or coupled with the cell surface (interpreted as a labelled cell comprising a second reporter agent, claim 11) (paragraph [0197]).
Regarding claim 14, Mikkelsen teaches that the term "barcode," as used herein, generally refers to a label, or identifier, that can be part of an analyte to convey information about the analyte, such that a barcode can be a tag attached to an analyte (e.g., nucleic acid molecule) or a combination of the tag in addition to an endogenous characteristic of the analyte (e.g., size of the analyte or end sequences), wherein the barcode can be unique and/or barcodes can have a variety of different formats, for example, barcodes can include: polynucleotide barcodes; random nucleic acid and/or amino acid sequences; and synthetic nucleic acid and/or amino acid sequences; and a barcode can be attached to an analyte in a reversible or irreversible manner and/or they can be added to, for example, a fragment of a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) sample before, during, and/or after sequencing of the sample (interpreted as a plurality of barcode nucleic acid molecule further comprising a second barcode nucleic acid molecule, claim 14) (paragraph [0093]). Mikkelsen teaches that
barcodes, can be previously, subsequently or concurrently delivered to the partitions that hold the compartmentalized or partitioned cells or cellular derivatives, in order to allow for the later attribution of the characteristics of the individual cells to the particular compartment (interpreted as a plurality of barcode nucleic acid molecule further comprising a second barcode nucleic acid molecule, claim 14) (paragraph [0107]). Mikkelsen teaches that Figure 4 shows a first nucleic acid 404 from a first cell 400, and a second nucleic acid 406 from a second cell 402 are each partitioned along with their own sets of barcode oligonucleotides as described above (interpreted as a plurality of barcode nucleic acid molecule further comprising a second barcode nucleic acid molecule, claim 14) (paragraph [0190]; and Figure 4). Mikkelsen teaches that a barcode sequence can be appended to the 3' end of a first subset of the template polynucleotides, and a barcode sequence can be appended to the 5' end of a second subset of the template polynucleotides, wherein the first subset of template polynucleotides and the second subset of template polynucleotides are appended to barcode sequences in the same partition (interpreted as a plurality of barcode nucleic acid molecule further comprising a second barcode nucleic acid molecule, claim 14) (paragraph [0242]).
Regarding claim 16, Mikkelsen teaches that each cell's nucleic acids 404 and 406 is then processed to separately provide overlapping set of second fragments of the first fragment(s), e.g., second fragment sets 408 and 410, such that this processing also provides the second fragments with a barcode sequence that is the same for each of the second fragments derived from a particular first fragment, wherein the barcode sequence for second fragment set 408 is denoted by "1" while the barcode sequence for fragment set 410 is denoted by "2", such that a diverse library of barcodes can be used to differentially barcode large numbers of different fragment sets (interpreted as generating a second barcoded nucleic acid molecule from the second barcode nucleic acid molecule and the second reporter nucleic acid molecule, claims 14 and 16) (paragraph [0191]; and Figure 4). Mikkelsen teaches that different members of the library of potential cell binding ligands, e.g., antibodies, antibody fragments, cell surface receptor binding molecules, or the like, can be associated with a first set of nucleic acid reporter molecules, e.g., an antibody to a first type of cell surface protein or receptor can have a first known reporter oligonucleotide sequence, where a different reporter oligonucleotide sequence, while an antibody to a second receptor protein can have a different known reporter oligonucleotide sequence associated with it, such that different members of the library can be characterized by the presence of a different oligonucleotide sequence label (interpreted as generating a second barcoded nucleic acid molecule from a second barcoded nucleic acid molecule and a reporter nucleic acid molecule, claim 16) (paragraph [0195]). Mikkelsen teaches a library of antibodies, antibody fragments, or other molecules having a binding affinity to the cell surface proteins or antigens (or other cell features) for which the cell is to be characterized (also referred to herein as cell surface feature binding groups), such that these affinity groups are referred to herein as binding groups, wherein the binding groups can include a reporter molecule that is indicative of the cell surface feature to which the binding group binds including a binding group type that is specific to one type of cell surface feature will comprise a first reporter molecule, while a binding group type that is specific to a different cell surface feature will have a different reporter molecule associated with it, wherein these reporter molecules will comprise oligonucleotide sequences (interpreted as generating a second barcoded nucleic acid molecule from a second barcoded nucleic acid molecule and a reporter nucleic acid molecule, claim 16) (paragraph [0279], lines 7-20). Mikkelsen teaches that the reporter oligonucleotides can be selected to provide barcoded products that are already sized and configured to be analyzed on a sequencing system (interpreted as generating a second barcoded nucleic acid molecule from a second barcoded nucleic acid molecule and a reporter nucleic acid molecule, claim 16) (paragraph [0282]).
Mikkelsen does not specifically exemplify a specific reporter agent configured to couple to a secreted analyte (claim 8, in part).
Regarding claim 8 (in part), Fandl teaches a method of detecting and isolating cells that produce a secreted protein of interest (POI), for example, an antibody, comprising: (a) providing a eukaryotic cell comprising: (i) a nucleic acid encoding the POI, and (ii) a nucleic acid encoding a cell surface capture molecule, which comprises a membrane anchor and is capable of binding the POI; (b) culturing the cell under conditions in which the POI and cell surface capture molecule are expressed, and a POI-cell surface capture molecule complex is formed intracellularly and displayed on the cell surface; (c) detecting the surface displayed POI by contacting the cells with a detection molecule, which binds the POI; and (d) isolating cells based on the detection molecule (interpreted as a labeled cell; cell surface capture molecule; expressing/secrete analyte; forming a complex on the cell surface; and interpreting a detection molecule as a reporter, claims 1 and 8) (Abstract). Fandl teaches that the method allows rapid isolation of high expression recombinant antibody-producing cell lines, or can be applied directly to rapid isolation of specific hybridomas (col 1, lines 32-37). Fandl teaches a high-throughput screening method for the rapid isolation of those cells that secrete protein by directly screening for the protein of interest (POI), which also allows for the convenient monitoring of POI expression on a single-cell basis during the manufacturing process, which can be directly applied to screening of antibody producing cells and/or directly applied to screening of cells producing modified T cell receptors, such as, for example, cells that produce soluble forms of T cell receptors (col 2, lines 6-15). Fandl teaches that the methods of the invention are useful for identification of B-cells and derivatives thereof, or hybridomas that express secreted antibodies of a desired specificity, affinity or isotype; as well as, for isolation of cells that express desired levels of an antibody or antibody fragments, wherein detection of the cells with the displayed POI can be accomplished through the use of any molecule capable of directly or indirectly binding the displayed POI, wherein such detection molecules can facilitate the detection and/or isolation of the cells displaying the POI; and two molecules that bind each other and are differentially labeled are utilized, such that the detection and/or isolation can be accomplished through standard techniques known in the art (interpreted as a reporter molecule configured to couple to the secreted analyte, claim 8) (col 3, lines 49-62). Fandl teaches that the method of the invention provides substantial advantages over current methods for isolation and identification of protein-secreting cells, such that the cells that secrete antibodies can be rapidly and conveniently isolated based on desired specificity, avidity, or isotype, wherein the amount of secreted protein produced can be directly quantified (col 8, lines 33-38). Fandl teaches that the
invention is based on the production of a cell line that expresses a molecule, localized to the cell surface, which binds the POI, such that the cell surface displayed POI can then be detected by labeling with various detection molecules, wherein the amount of POI displayed on the cell surface, under specific conditions, is a direct measure of the total amount of POI secreted, such that POI producers can then be isolated from non-producers, and levels of production or POI characteristics can be differentiated, wherein the advantage of the invention is that it directly quantifies the secreted POI rather than indirectly measuring the mRNA (col 9, lines 54-64). Fandl teaches that as the cell secretes the POI, these cell surface capture molecules bind it, or complexes of POI and cell surface capture molecules can form intracellularly and then get secreted, such that binding can occur in an autocrine manner or while being secreted (col 10, lines 1-5).
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 isolating and identifying cells that secrete a protein of interest as exemplified by Fandl, 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 of analyzing individual cells or cell populations including the partitioned analysis and characterization of cellular contents including barcoded nucleic acids from a cell as disclosed by Mikkelsen to include the methods of isolating and identifying cells that produce a secreted protein of interest and/or monitoring of a POI on a single cell basis as taught by Fandl with a reasonable expectation of success in rapidly and conveniently isolating individual cells and/or cell populations that produce secreted proteins based on desired specificity, avidity, or isotype; in constructing and/or detecting a nucleic acid molecule that encodes a cell surface capture molecule capable of binding a protein of interest; in directly quantifying secreted proteins; and/or in the high-throughput screening, identification, and/or analysis of nucleic acid fragments originating from specific cells including cells comprising different binding ligands and/or reporter molecules.
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.
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.
Claims 1-3, 6, 8, 10, 11, 14 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 7, 8, 10, 11, 14, 17 and 53 of copending US Patent Application No. 18/297137. US18/297137 teaches - a method of single cell analysis, comprising: a) contacting an antibody-secreting cell with a reporter agent comprising a reporter nucleic acid molecule to provide a labelled cell, wherein the reporter nucleic acid molecule comprises a reporter sequence corresponding to the reporter agent, wherein the labelled cell comprises a complex coupled to a surface of the cell, and wherein the complex comprises (i) a capture agent, (ii) a secreted antibody or antigen binding fragment thereof, and (iii) the reporter agent; b) partitioning the labelled cell in a partition, wherein the partition comprises a plurality of barcode nucleic acid molecules which comprise a common partition-specific barcode sequence; and c) in the partition, generating a barcoded nucleic acid molecule from a barcode nucleic acid molecule of the plurality of barcode nucleic acid molecules and the reporter nucleic acid molecule, wherein the barcoded nucleic acid molecule comprises the reporter sequence or a complement thereof and the common partition-specific barcode sequence or a complement thereof (claim 1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US17/716134 and the copending claims of US18297137 encompass a method comprising contacting a cell with a reporter agent, wherein the labelled cell comprises a complex coupled to the cell surface; partitioning a labelled cell in a partition comprising a plurality of barcoded nucleic acids; and generating a barcoded nucleic acid molecule.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 6, 8, 10, 11, 14 and 16 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684