Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Pursuant to a preliminary amendment, filed August 3, 2023, claims 16 – 32 are currently pending.
Priority
The present application filed April 24, 2023 is a CON of US Patent Application 15/835,738, filed December 8, 2017 (now abandoned), which is a CON of US Patent Application 11/665,099 (now US Patent 9839890), filed December 15, 2008, which is a 35 U.S.C. 371 national stage filing of International Application No. PCT/GB2005/003927, filed on October 12, 2005, which is a CON of US Patent Application 10/962,952, filed October 12, 2004 (now abandoned), which is a CON of PCT/GB04/01352, filed March 31, 2004, which claims the benefit of UK Patent GB0307428.3, filed March 31, 2003.
Acknowledgment is made of applicant's claim for foreign priority based on an application (GB0307428.3) filed in the United Kingdom on March 31, 2003.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, the instant as-filed Specification and claims, filed April 24, 2023, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 16 does not have support for; “wherein each microcapsule comprises a microbead and a cell, and wherein each microbead comprises one of a plurality of compounds”; “the reaction involves the compound and a molecule associated with the cell;” and “identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction.” Therefore, the priority date for the presently claimed invention is April 24, 2023, the filing date of US Patent Application 18/305,932.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 16 of the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on February 9, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
The following reference has not been considered by the examiner, as indicated on Form PTO 1449.
Foreign Reference 26: JP 55125472, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 27: JP 56-124052, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 28: JP 59-102163, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 31: JP 7-489, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 43: WO 02060591, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 45: WO 02/16017, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 3: CH 563807, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 45: DE 4308839, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 21: JP 2000-271475, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 2: WO 02/066992, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Foreign Reference 7: WO 2007012638, of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
Non-Patent Literature 29: Japanese Office Action JP 2006-509830 of IDS filed on February 9, 2024 has not been considered because and English translation of the document has not been provided.
All other documents in said Information Disclosure Statement were considered as noted by the Examiner initials in the copy attached hereto.
Claim Objections/Rejections
Claim Interpretation: the term “wherein each microbead comprises one of a plurality of compounds” as recited in claim 16 is interpreted to refer to: (i) each bead comprises a single compound; and/or (ii) each bead comprises a plurality of compounds of single type.
Specification Objection
The disclosure is objected to because of the following informalities: the as-filed Specification, filed April 24, 2023, does not include the current status of the following Applications: US Patent Application No. 15/835,738 (now abandoned); US Patent Application No. 11/665,099 (now US Patent 9839890); and US Patent Application 10/962,952, filed October 12, 2004 (now abandoned).
Appropriate correction is required.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 16 – 32 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 16 is indefinite for the recitation of the term “wherein each microbead comprises a microbead, and a cell, and wherein each microbead comprises one of a plurality of compounds” such as recited in claim 16, lines 2-3 because the as-filed Specification does not recite a microcapsule comprising a microbead, a cell, and a plurality of compounds and, thus, the metes and bounds of the claim cannot be determined.
Claim 16 is indefinite for the recitation of the term “wherein the reaction involves the compound and a molecule associated with the cell” such as recited in claim 16, lines 4-5 because the as-filed Specification does not recite a reaction that involves the compound and a molecule associated with the cell and, thus, the metes and bounds of the claim cannot be determined.
Claim 16 is indefinite for the recitation of the term “the compound” such as recited in claim 16, lines 4-5 and 7. There is insufficient antecedent basis for the term “the compound” in the claim because claim 16, line 3 recites the term “a plurality of compounds.” The Examiner suggests that Applicant amend the claim to recite, for example, “a portion of the plurality of compounds.”
Claim 16 is indefinite for the recitation of the term “identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction” such as recited in claim 16, lines 7-8 because the as-filed Specification does not recite identifying microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction and, thus, the metes and bounds of the claim cannot be determined.
Claim 16 is indefinite for the recitation of the term “the microbeads” such as recited in claim 16, line 7. There is insufficient antecedent basis for the term “the microbeads” in the claim because claim 16, line 2 recites the term “a plurality of microbeads.”
Claim 17 is indefinite for the recitation of the term “the plurality of microcapsules is surrounded by an immiscible fluid comprising a surfactant” such as recited in claim 17, lines 1-2 because claim 17 depends from instant claim 16, wherein claim 16 does not recite any specific type of microcapsule, fluids, a microfluidic device, channels, droplets, etc. and, thus, the metes and bounds of the claim cannot be determined.
Claim 26 is indefinite for the recitation of the term “wherein the reaction is performed in a fluid channel” such as recited in claim 26, line 1 because claim 26 depends from instant claim 16, wherein claim 16 does not recite a microfluidic device, an assay device, a flow cytometer, fluids, channels, etc. and, thus, the metes and bounds of the claim cannot be determined.
Claim 28 is indefinite for the recitation of the term “further comprising expressing the gene to form a gene product” in claim 28, lines 1-2 because the method as it relates to instant claim 16 is unclear. It is unclear whether, in addition to the reaction, the gene is expressed; whether the product of the reaction is acts on a gene that is expressed; and/or exactly what the method of claim 16 further comprises and, thus, the metes and bounds of the claim cannot be determined.
Claims 18-25 and 27-32 are indefinite insofar as they ultimately depend from instant claim 16.
Claim Rejections - 35 USC § 112, 1st paragraph – 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 16-32 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 16 recites in part: “wherein each microcapsule comprises a microbead and a cell, and wherein each microbead comprises one of a plurality of compounds”; “the reaction involves the compound and a molecule associated with the cell;” and “identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction” in lines 2-8. 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 the microcapsules comprising a cell, a microbead, and one of a plurality of compounds attached to the microbead; a reaction involves the compound and a molecule associated with the cell; and/or identifying microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction as recited in instant claim 16. The instant as-filed Specification, filed April 24, 2023 teaches, for example: identifying subsets of candidate molecules” (pg. 2, line 28); “identifying subsets of primary compounds which react to form secondary compounds” (pg. 5, line 9); “compounds may be compartmentalized in different ways to achieve encapsulation of multiple copies of two or more compounds into microcapsules” (pg. 6, lines 22-23); “Alginate/polylysine microcapsules…an effective method of encapsulating living cells and tissues” (pg. 35, line 31; and pg. 36, lines 1-2); “the fluid may also contain other species, for example, certain molecular species (e.g., as further discussed below), cells, particles, etc.” (pg. 39, lines 23-24); “cells can be compartmentalized in microcapsules… compartments containing compounds with the desired effect on the cell(s)” (pg. 74, lines 23-28); and
“microcapsules or microbeads are optically tagged, flow cytometry can also be used to identify the compound or compounds in the microcapsule or coated on the microbeads” (pg. 76, lines 9-10). No such corresponding teaching a microcapsule comprising a cell, microbead, plurality of compounds; reacting a compounds with a molecule associated with the cell; and/or identifying microbeads comprising a portion of the compounds causing a selectable change in a product of a reaction is taught by the instant as-filed Specification and/or the original claims.
A claim-by-claim analysis and for dependent claim 28, and a method step by method step analysis regarding where support can be found for the broad teachings of partitions comprising a nucleic acid molecule comprising a epigenetic feature, using an epigenetic feature and a barcode sequence to determine an epigenetic state, partitions comprising a barcode nucleic acid molecule comprising a barcode sequence or complement thereof, and/or processing a barcode nucleic acid or derivative thereof to identify an epigenetic feature in the originally filed specification is respectfully suggested. See MPEP § 2163 particularly § 2163.06.
Claims 16-32 will remain rejected until Applicant cancels all new matter.
Claim Rejections - 35 USC § 112, 4th paragraph
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 17 and 26 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 17 recites (in part): “wherein each of the plurality of microcapsules is surrounded by an immiscible fluid comprising a surfactant” in lines 1-2 because claim 17 depends from instant claim 16, wherein claim 16 does not recite any specific type of microcapsule, fluids, a microfluidic device, channels, droplets, etc.. Thus, claim 17 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 26 recites (in part): “wherein the reaction is performed in a fluid channel” in lines 1-2 because claim 26 depends from instant claim 16, wherein claim 16 does not recite channels, a microfluidic device, fluids, an assay device, etc. Thus, claim 26 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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 16-21 and 23-32 are rejected under 35 U.S.C. 102(b) as being anticipated by Quake et al. (hereinafter “Quake”) (US Patent Application Publication 20020058332, published May 16, 2002).
Regarding claim 16, Quake teaches devices and methods to compartmentalize small droplets of aqueous solution within microfluidic channels filled with oil (interpreted as forming an aqueous microcapsule within an immiscible oil; and microfluidic channel, claim 26) (paragraph [0003], lines 3-6). Quake teaches that preferred embodiments are used to sort or evaluate molecules such as nucleic acids, proteins, or cells, such as bacteria or pathogens using the microfluidic devices and methods of the invention (paragraph [0004]). Quake teaches that individual particles or molecules can be separately compartmentalized inside individual droplets, such that the droplets can be analyzed, combined with other droplets (e.g., to react droplet contents) and/or sorted, as desired (interpreted as forming microcapsules), wherein preferably, each droplet of the multi-phase mixture encapsulates a single particle (interpreted as not more than one microbead), such that molecules include, for example, polynucleotides, polypeptides, enzymes, substrates or mixtures thereof, cells or viral particles, or mixtures thereof (interpreted as forming a microcapsule; immiscible oil; comprising a cell and molecule/enzyme; not more than one microbead; and multiple copies of an enzyme-modulating compound, claims 16 and 19) (paragraphs [0012], lines 11-18; [0021]; and [0050]). Quake teaches that
particles (including, e.g., cells, virions and molecules) are sorted and/or analyzed by encapsulating the particles into individual droplets (e.g., droplets of aqueous solution in oil), and these droplets are then sorted, combined and/or analyzed in a microfabricated device (interpreted as identifying microbeads comprising compounds; and comprising cells, molecules, and beads, claim 16) (paragraph [0059]). Quake teaches that aqueous droplets are used as micro-reactors for chemical reactions (interpreted as performing a reaction, claim 16) (paragraph [0095]). Quake teaches that a reporter can include any substance on or in a cell that causes a detectable reaction, for example, by acting as a starting material, reactant, or catalyst for a reaction which produces a detectable product (interpreted as performing a reaction; and identifying microbeads comprising compounds that cause a selectable change in a product of a reaction, claim 16) (paragraph [0062], lines 27-30). Quake teaches that enzymes can be analyzed and/or sorted by the extent to which they catalyze chemical reaction of a substrate and, conversely, a substrate can be analyzed and sorted by the level of chemical reactivity catalyzed by an enzyme (interpreted as microbeads; compounds attached to the microbeads; and performing a reaction, claim 16) (paragraph [0106], lines 12-16). Quake teaches that cells pass through the main flow pathway, which terminates through a common waste chamber; and that samples collected at the outlet region of the different branch channels contain pools of cells expressing defined levels of each of the three markers (corresponding to pooling in a common compartment, claim 16) (paragraph [0162], lines 6-9). Quake teaches in Example 5, that cells are labeled with an optically detectable reporter which is analyzed and interpreted to determine whether the cell having the reporter should be sorted, wherein the reporter can function in a variety of ways to effectively emit or display a readable signal that can be detected by the detection region (interpreted as comprising a cell; optically detectable; and a identifying a selectable change, claims 16 and 32) (paragraph [0164]). Quake teaches that the cells can produce a reporter in vivo (e.g., a fluorescent compound) through interaction with a reagents added to the fluid medium, such as cells containing a gene for an oxygenase enzyme can catalyze a reaction on an aromatic substrate such as benzene or naphthalene with the net result that the fluorescence, or another detectable property of the substrate will change (interpreted as the cell comprises a molecule; and performing a reaction, claim 16) (paragraph [0170], lines 1-9).
Regarding claims 17 and 26, Quake teaches devices and methods to compartmentalize small droplets of aqueous solution within microfluidic channels filled with oil (interpreted as forming an aqueous microcapsule within an immiscible oil; and microfluidic channel, claims 17 and 26) (paragraph [0003], lines 3-6). Quake teaches that Figures 18A-C are photomicrographs showing droplets of aqueous solution in a flow of oil (hexadecane with 2% Span 80 surfactant) in a microfluidic device with rectangular channels (interpreted as an immiscible fluid comprising a surfactant; and a channel, claim 17) (paragraph [0041]; and Figures 18A-C).
Regarding claim 19, Quake teaches that individual particles or molecules can be separately compartmentalized inside individual droplets, such that the droplets can be analyzed, combined with other droplets (e.g., to react droplet contents) and/or sorted, as desired (interpreted as forming microcapsules), wherein preferably, each droplet of the multi-phase mixture encapsulates a single particle (interpreted as not more than one microbead, claim 19) (paragraph [0012]).
Regarding claim 18, Quake teaches that the microfabricated devices of the invention generates round, monodisperse droplets (interpreted as monodisperse microcapsules, claim 18) (paragraph [0093], lines 1-3).
Regarding claims 20 and 21, Quake teaches that beads can be used in sorting a library of compounds produced by combinatorial chemistry, wherein charged beads can be used to facilitate flow or detection, or as a reporter (interpreted as beads comprising compounds, claims 20 and 21) (paragraph [0060], lines 22-28). Quake teaches that fluorescent dyes are examples of optically-detectable reporters, where a number of known dyes selectively bind to nucleic acids, proteins and sugars (interpreted as the compounds are nucleic acids; and labeled compounds, claims 20 and 21) (paragraph [0166], lines 1-3).
Regarding claims 23, 24 and 25, Quake teaches that microfabrication permits other technologies to be integrated or combined with flow cytometry on a single chip including PCR (interpreted as amplification including PCR; and encompassing reverse transcription, claims 23, 24 and 25) (paragraph [0080]).
Regarding claim 26, Quake teaches devices and methods to compartmentalize small droplets of aqueous solution within microfluidic channels filled with oil (interpreted as fluid channel, claim 26) (paragraph [0003], lines 3-6). Quake teaches that the strength of the signal can indicate the size of a molecule, or the potency or amount of an enzyme expressed by a cell, or a positive or negative reaction such as binding or hybridization of one molecule to another, or a chemical reaction of a substrate catalyzed by an enzyme, such that in response to the signal, data can be collected and/or a flow control can be activated to divert a droplet into one branch channel or another (interpreting the reaction to take place in a fluid channel, claim 26) (paragraph [0078]).
Regarding claims 27 and 28, Quake teaches that the cells can produce a reporter in vivo (e.g., a fluorescent compound) through interaction with a reagents added to the fluid medium, such as cells containing a gene for an oxygenase enzyme can catalyze a reaction on an aromatic substrate such as benzene or naphthalene with the net result that the fluorescence, or another detectable property of the substrate will change (interpreted as the molecule comprises a gene to form a gene product, claims 27 and 28) (paragraph [0170], lines 1-9).
Regarding claims 29-31, Quake teaches that the signal is in the form of a marker that associates within or binds to a particular cell type, wherein the signal acts to identify the cell as having a particular characteristic, e.g., a protein (receptor) or saccharide, such that the reporter signal from a given cell is proportional to the amount of a particular characteristic including wherein the reporter can be an antibody, a receptor or a ligand to a receptor (which bind to a protein or sugar), or a fragment thereof, each having a detectable moiety, such as a dye that fluoresces; and/or the reporter can bind to a structure on the surface or within the cell of interest, and since the antibody contains a detectable reporter, any cell to which the reporter is bound would be detectable by the detection region of the device as the cell flows past such region (interpreting the gene product to be a protein; an antibody; and locating within or outside the cell, claims 19-31) (paragraph [0165]).
Regarding claim 32, Quake teaches in Example 5, that cells are labeled with an optically detectable reporter which is analyzed and interpreted to determine whether the cell having the reporter should be sorted, wherein the reporter can function in a variety of ways to effectively emit or display a readable signal that can be detected by the detection region (interpreted as comprising a cell; optically detectable; and a identifying a selectable change, claims 16 and 32) (paragraph [0164]).
Quake does not specifically exemplify that compounds comprise a primer sequence (claim 22).
Quake 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(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 16-32 are rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al. (hereinafter “Griffiths”) (International Application WO9902671, published January 21, 1999) in view of Ismagilov et al. (hereinafter “Ismagilov”) (US Patent No. 7129091, issued October 31, 2006; effective filing date May 9, 2002) as evidenced by Liabakk et al. (hereinafter “Liabakk”) (Journal of Immunological Methods, 1990, 134, 253-259).
Regarding claim 16, Griffiths teaches that the invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalizing genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having a desired activity, wherein the invention enables the in vitro evolution of nucleic acids by repeated mutagenesis and iterative applications of the method of the invention (interpreted as microcapsules comprising gene; and expressing gene products, claim 16) (Abstract). Griffiths teaches that evolution requires the generation of genetic diversity (diversity in nucleic acid) followed by the selection of those nucleic acids which result in beneficial characteristics; and because the nucleic acid and the activity of the encoded gene product of an organism are physically linked (the nucleic acids being confined within the cells which they encode) multiple rounds of mutation and selection can result in the progressive survival of organisms with increasing fitness (interpreted as genetic elements within cells, claim 16) (pg. 3, lines 9-14). Griffiths teaches that a genetic element is a molecule or molecular construct comprising a nucleic acid, wherein the nucleic acid component of the genetic element can be linked, covalently or non-covalently, to one or more molecules or structures, including proteins, chemical entities and groups, solid-phase supports such as magnetic beads, and the like (interpreted as a microcapsule comprising a microbead comprising one of a plurality of compounds; and a molecule associated with a cell, claim 16) (pg. 4, lines 17-22). Griffiths teaches conventional screening techniques to identify compounds which are capable of interacting with the gene products identified by the first aspect of the invention, such that the gene product expressing cells can be employed for the identification of compounds, particularly small molecular weight compounds (interpreted as comprising compounds and molecules, claim 16) (pg. 25, lines 17-19 and 24-25). Griffiths teaches that microcapsule sorting is applied to sorting systems which rely on a change in optical properties, such that an alteration in the optical properties of the microcapsule resulting from a reaction leading to changes in absorbance, luminescence, phosphorescence, or fluorescence associated with the microcapsule, wherein fluorescence activated sorting is employed to sort microcapsules in which the production of a gene product having a desired activity is accompanied by the production of a fluorescent molecule in the cell (interpreted as a microcapsule comprising a cell; a reaction; reaction product; and identifying a microcapsule, claim 16) (pg. 33, lines 4-13). Griffiths teaches that genetic elements are sorted following pooling of the microcapsules into one or more common compartments, such that a gene product having the desired activity modifies the genetic element which encoded it (and which resides in the same microcapsule) in such a way as to make it selectable in a subsequent step (interpreted as pooling microcapsules into a common compartment; and causing a selectable change, claim 16) (pg. 6, lines 9-12). Griffiths teaches that biotinylated nucleic acid can be coupled to a polystyrene microbead (0.035 to 0.21mm in diameter) that is coated with avidin or streptavidin, that will therefore bind the nucleic acid with very high affinity (interpreted as microbeads comprising a avidin or streptavidin as a plurality of compounds; and interpreting nucleic acids as molecules associated with a cell, claim 16) (pg. 20, lines 9-11). Griffiths teaches that the product of the reaction being selected can be the substrate or cofactor for a second enzyme-catalyzed reaction, such that the enzyme to catalyze the second reaction can either be translated in situ in the microcapsules or incorporated in the reaction mixture prior to microencapsulation, such that only when the first reaction proceeds will the coupled enzyme generate a selectable product, wherein the concept of coupling can be elaborated to incorporate multiple enzymes, each using as a substrate the product of the previous reaction, which allows for selection of enzymes that will not react with an immobilized substrate; and can also be designed to give increased sensitivity by signal amplification if a product of one reaction is a catalyst or a cofactor for a second reaction, or series of reaction leading to a selectable product (interpreted as identifying microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction, claim 16) (pg. 29, lines 28-30; and pg. 30, lines 1-8).
Regarding claim 17, Griffiths teaches that the microcapsule is formed by phase partitioning such as with water-in-oil emulsions (interpreted as microcapsule is surrounded by an immiscible fluid, claim 17) (pg. 32, line 31; and pg. 33, line 1). Griffiths teaches that the emulsion can be stabilized by addition of one or more surface-active agents (surfactants), termed emulsifying agents and act at the water/oil interface to prevent (or at least delay) separation of the phases, wherein many oils and many
emulsifiers can be used for the generation of water-in-oil emulsions; a recent compilation listed over 16,000 surfactants, many of which are used as emulsifying agents (Ash and Ash, 1993); and suitable oils include light white mineral oil and non-ionic surfactants (interpreted as an immiscible fluid comprising a surfactant, claim 17) (pg. 15, lines 7-14).
Regarding claim 18, Griffiths teaches that examples include selection by binding including techniques based on magnetic separation, for example, using Dynabeads including binding to Streptavidin M-280 Dynabeads (pg. 19, line 30; pg. 20, line 1; and pg. 46, lines 10-11), where it is known that Dynabeads are monodisperse as evidenced by Liabakk (Abstract).
Regarding claim 19, Griffiths teaches that an in vitro transcription/translation reaction mixture containing a library of genetic elements linked to a substrate for the reaction being selected is dispersed to form a water-in-oil emulsion with typically one genetic element per aqueous compartment (interpreted as microcapsules comprising no more than one microbead, claim 19) (pg. 10, lines 4-8). Griffiths teaches that the substrate (or one of the substrates) is present in each microcapsule unlinked to the genetic element, but has a molecular "tag" (for example biotin, DIG or DNP) (interpreted as microcapsules comprising no more than one microbead, claim 19) (pg. 20, lines 29-31).
Regarding claim 20, Griffiths teaches that a genetic element is a molecule or molecular construct comprising a nucleic acid, wherein the nucleic acid component of the genetic element can be linked, covalently or non-covalently, to one or more molecules or structures, including proteins, chemical entities and groups, solid-phase supports such as magnetic beads, and the like (interpreted as a microcapsule comprising a microbead comprising one of a plurality of compounds are nucleic acids, claim 20) (pg. 4, lines 17-22).
Regarding claim 21, Griffiths teaches that the genetic element is a molecule or construct selected from the group consisting of a DNA molecule, an RNA molecule, a partially or wholly artificial nucleic acid molecule consisting of exclusively synthetic or a mixture of naturally-occurring and synthetic bases, anyone of the foregoing linked to a polypeptide, and anyone of the foregoing linked to any other molecular group or construct, wherein the other molecular group or construct can be selected from the group consisting of nucleic acids, polymeric substances, particularly beads, for example polystyrene beads, magnetic substances such as magnetic beads, labels, such as fluorophores or isotopic labels, chemical reagents, binding agents such as macrocycles and the like (interpreted as nucleic acids comprising a label, claim 21) (pg. 19, lines 6-14).
Regarding claims 22 and 25, Griffiths teaches that the nucleic acid molecules can be linked to a ligand or a substrate through biotinylation, such as done by PCR amplification with a 5’-biotinylation primer such that the biotin and the nucleic acid are covalently linked (interpreted as where the compounds comprising a primer sequence; and primers for PCR, claims 22 and 25) (pg. 20, lines 4-6).
Regarding claim 23, Griffiths teaches that the E. coli folA gene encoding dihydrofolate reductase (DHFR) is PCR-amplified using oligonucleotides EDHFRFo and EDHFRBa (interpreted as wherein the reaction is an amplification reaction, claim 22) (pg. 20, lines 4-6).
Regarding claims 24 and 29, Griffiths teaches that where the nucleic acid is RNA, expression can refer to the replication of this RNA into further RNA copies, the reverse transcription of the RNA into DNA and optionally the transcription of this DNA into further RNA molecule(s), as well as optionally the translation of any of the RNA species produced into protein, where expression is performed by one or more processing selected from the group consisting of transcription, reverse transcription, replication and translation (interpreting the reaction to be a reverse transcription reaction; and where the product is a protein, claims 24 and 29) (pg. 4, lines 30-31; and pg. 5, lines 1-4).
Regarding claim 26, Griffiths teaches that emulsions are spun in a microfuge at 13,000 rpm for 5 minutes and the mineral oil removed leaving the concentrated emulsion at the bottom of the tube (interpreted as a reaction being performed in a fluid channel, claim 26) (pg. 41, lines 29-30).
Regarding claims 27 and 28, Griffiths teaches that the invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalizing genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having a desired activity, wherein the invention enables the in vitro evolution of nucleic acids by repeated mutagenesis and iterative applications of the method of the invention (interpreted as microcapsules; molecules comprise a gene; and expressing gene products, claims 27 and 28) (Abstract).
Regarding claim 30, Griffiths teaches that pools of naturally occurring genetic elements can be cloned from genomic DNA or cDNA (Sambrook et al., 1989) ; for example, phage antibody libraries, made by PCR amplification repertoires of antibody genes from immunized or unimmunized donors have proved very effective sources of functional antibody fragments (interpreted as where the protein is an antibody, claim 30) (pg. 22, lines 6-9). Griffiths teaches the generation of phage-display antibodies specific for tetrahydrofolate (interpreted as where the protein is an antibody, claim 30) (pg. 49, line 19).
Regarding claim 31, Griffiths teaches that the nucleic acid and the activity of the encoded gene product of an organism is physically linked (the nucleic acids being confined within the cells which they encode) (interpreted as an antibody being within the cell, claim 31) (pg. 1, lines 10-12). Griffiths teaches that genetic elements according to the invention advantageously encode enzymes, preferably of pharmacological or industrial interest, activators or inhibitors, especially of biological systems, such as cellular signal transduction mechanisms, antibodies and fragments thereof (interpreted as an antibody being within the cell, claim 31) (pg. 23, lines 6-8).
Regarding claim 32, Griffiths teaches that microcapsule sorting is applied to sorting systems which rely on a change in optical properties, such that an alteration in the optical properties of the microcapsule resulting from a reaction leading to changes in absorbance, luminescence, phosphorescence, or fluorescence associated with the microcapsule, wherein fluorescence activated sorting is employed to sort microcapsules in which the production of a gene product having a desired activity is accompanied by the production of a fluorescent molecule in the cell (interpreting identifying as optically identifying, claim 32) (pg. 33, lines 4-13).
Griffiths does not specifically exemplify where a reaction is performed in a microfluidic channel (claim 26, in part).
Regarding claim 26 (in part), Ismagilov teaches that the present invention provides micro- fabricated substrates and methods of conducting reactions within these substrates, wherein the reactions occur in plugs transported in the flow of a carrier-fluid (interpreted as reactions in channels, claim 26) (Abstract). Ismagilov teaches that microfluidics deals with the transport of fluids through networks of channels, typically having micrometer dimensions, wherein microfluidic systems (sometimes called labs-on-a-chip) find applications in microscale chemical and biological analysis (micro-total analysis systems), such that the main advantages of microfluidic systems are high speed and low consumption of reagents, and thus are very promising for medical diagnostics and high-throughput screening including highly parallel arrays of microfluidic systems are used for the synthesis of macroscopic quantities of chemical and biological compounds (col 1, lines 15-26). Ismagilov teaches that biological particles or molecules such as cells and virions can be sorted according to whether they contain or produce a particular protein, by using an optical detector to examine each cell or virion for an optical indication of the presence or amount of that protein, wherein a chemical itself can be detectable, for example by a characteristic fluorescence, or it can be labeled or associated with a tag that produces a detectable signal when, for example, a desired protein is present, or is present in at least a threshold amount (col 31, lines 35-44).
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 the benefits of microfluidic as exemplified by Ismagilov, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the method of isolating one or more genetic elements encoding a gene product having a desired activity including compartmentalizing genetic elements into microcapsules; and sorting the genetic elements having the desired activity as disclosed by Griffiths to include the microfluidic systems including conducting reactions within a channel of a substrate as taught by Ismagilov with a reasonable expectation of success in producing a high-throughput, high speed, low reagent consumption process for the efficient isolation, detection, amplification, and/or quantification of reaction products associated with chemical and/or biological reactions.
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.
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Claims 16-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-17 of U.S. Patent No. 9448172, which teaches a method comprising: introducing an aqueous fluid comprising a target enzyme and an aqueous fluid comprising small molecule compounds; encapsulating in a water-in-fluorocarbon oil microcapsules; introducing a fluorogenic substrate; conducting an enzyme catalyzed reaction to produce a product; producing a second product; and optically detecting a second product (claim 1). The small molecule compounds are attached to a microbead (claim 3). The microcapsules comprise a cell (claim 11).
Claims 1-10 of U.S. Patent No. 9839890, which teaches a method comprising: attaching first primary compounds to microbeads; attaching second primary compounds to microbeads; forming first water-in-fluorocarbon oil microcapsules; forming second water-in-fluorocarbon oil microcapsules; merging microcapsules; releasing in the microcapsules primary compounds from microbeads; forming secondary compounds; fusing microcapsules containing a target enzyme; and determining subsets of primary compounds that modulate the activity of the target enzyme (claim 1). Wherein the microcapsules further comprise a cell (claim 6). The target enzyme is associated with the cell (claim 7). Where the compounds comprise a fluorogenic substrate for the target enzyme (claim 10).
Claims 1-15 of U.S. Patent No. 10371699, which teaches a method comprising: proving an aqueous fluid comprising a repertoire of compounds; compartmentalizing the repertoire of compounds in microcapsules, which comprises a target cell; conducting a reaction; detecting a product of the reaction to identify a microcapsule containing the compound (claim 1). Fusing microcapsules (claim 3). Wherein the repertoire of compounds are attached to microbeads (claim 4). Each of the repertoire of compounds comprises a detectable tag (claim 13).
Claims 1-7 of U.S. Patent No. 106395598, which teaches a method comprising: providing a droplet generator to form a plurality of aqueous microcapsules comprising a genetic element and a cell; incubating the plurality of microcapsules to cause the genetic element to interact with a molecule associated with the cell; conducting an enzymatic reaction; and analyzing the genetic elements identified based on detection of a selectable change (claim 1). Where the genetic element is attached to a bead (claim 5).
Claims 1-7 of U.S. Patent No. 10705078, which teaches a method comprising: proving an aqueous fluid comprising a repertoire of compounds; compartmentalizing the compounds into microcapsules comprising a target cell; and determining an effect of the compounds on the target cell using a cell-based assay system, depending on the identity of the compound (claim 1). Where the compounds are attached to microbeads (claim 3). The microbeads comprise a detectable tag (claim 5). Releasing compounds from the microbeads (claim 6).
Claims 1-7 of U.S. Patent No. 11821109, which teaches a method comprising: compartmentalizing targets and microbeads linked to compounds in a plurality of aqueous microcapsules, wherein microbeads are coated with a single-type of compound; performing a reaction in each microcapsule; pooling the aqueous microcapsules into a common compartment; and selecting or identifying the compounds that bind the target (claim 1). Each compound comprises a tag (claim 7).
Although the claims at issue are not identical, they are not patentably distinct from each other because the pending claims of US Patents 9448172, 9839890, 10371699, 106395598, 10705078 and 11821109 encompass forming a plurality of microcapsules comprising a microbead comprising compounds and a cell; performing a reaction; pooling the microcapsules; and identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction.
Claims 16-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 116-125 of copending Application No. 16/921,789, which teaches a method comprising: providing an aqueous fluid comprising a repertoire of compounds; compartmentalizing the fluid into microcapsules; sorting the microcapsules according to activity of compound; determining the effect of one or more compounds on a target cell (claim 116). The microcapsules comprise the target cells (claim 118). The compounds are attached to microbeads (claim 119). The microbeads comprise a detectable tag (claim 121).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims of US Application 16/921,789 encompasses forming a plurality of microcapsules comprising a microbead comprising compounds and a cell; performing a reaction; pooling the microcapsules; and identifying the microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 16-32 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684