DETAILED ACTION
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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-9, 11-18, 20, 23-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 11 recite a functional characteristic of the labile tag: "operatively coupled.” The scope of the labile tag is unclear because the claims recite no structural limitations for the labile tag, but recites a functional limitation " operatively coupled.” This functional limitation does not set forth well-defined boundaries of the invention because they only state a problem solved or a result achieved. There is no clear-cut indication of the scope of the subject matter covered by the claim. The skilled artisan would not know which structures are encompassed by the claim because the specification does not provide any examples as to what are a “labile tag operatively coupled”. The use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim” and thus be indefinite. For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. See Federal Register /Vol. 76, No. 27 /Wednesday, February 9, 2011 /Notices, page 7165, first column.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5-9, 11-18, 20, 23-24 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The “labile tag” in claims 1 and 11 is defined functionally but lack a clear-cut indication of the scope of the subject matter embraced by the claim, as set forth above. Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. Unlimited functional claim limitations that extend to all means or methods of resolving a problem may not be adequately supported by the written description. In this case, the specification does not provide the particular structures that accomplish the functions recited in the claim. Therefore, the skilled artisan would not be apprised that the inventors had possession of the full scope of the claimed invention at the time the application was filed.
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, 5-9, 11-18, 20, 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12091706. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim similar composition and method of analyzing a sample comprising said composition.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 5-9, 11-18, 20, 23-24 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Schwartz et al. US 2012/0258881 (hereinafter "Schwartz").
As to claim 1 and 11, Schwartz discloses a composition comprising:
a plurality of analyte detection agents, each analyte detection agent comprising a labile tag operatively (para [0022]; "In certain embodiments, the conjugate may be formed with a covalent linkage. The covalent linkage may be selected from ... a disulfide"; para
[0056]; “a conjugate between an oligonucleotide and a cysteine-containing engineered protein, formed by reacting a cysteine-containing engineered protein with a thiol-reactive"). Schwartz discloses a labile tag coupled to the analyte detection agent (claim 1: "1. A method for assaying a target of a sample, comprising: i) providing to the sample: 1) a molecular probe, comprising a binding moiety conjugated to a first oligonucleotide sequence; and 2) a detectable component, comprising a signal generating moiety conjugated to a second oligonucleotide sequence that is complementary to the first oligonucleotide sequence of the molecular probe; ii) binding the target in the sample with the binding moiety of the molecular probe; iii) hybridizing the oligonucleotide sequence of the molecular probe with the second oligonucleotide sequence of the detectable component; and iv) detecting a signal generated from the hybridized detectable component using one or more of the following systems: microscopy, imaging, high content screening (HCS), mass cytometry"),
Further Schwartz discloses each labile tag comprising a signal that is different from each other labile tag and each analyte detection agent targeting a different analyte (para [0093]; "FIG. 54: is a schematic representation of the process of preassembly using pairs of complementary oligonucleotides in which a plurality of molecular probes and a plurality of detectable components are hybridized, i.e., preassembled, to form a plurality of preassembled molecular probe-detectable component hybrids, prior to contacting with a sample comprising one or more molecular targets. The preassembly process may be completed by individual preassembly, followed by pooling, then contacting with the sample, or alternatively, may be completed by pooling the plurality of
molecular probes and plurality of detectable components, preassembling by hybridization, and then contacting the pooled preassembled hybrids with the sample"; see sheet 56 fig 54);
Schwartz discloses wherein each labile tag is removable (para [0022]; "In certain embodiments, the conjugate may be formed with a covalent linkage. The covalent linkage may be selected from ... a disulfide"; para [0056]; "a conjugate between an
oligonucleotide and a cysteine-containing engineered protein, formed by reacting a cysteine-containing engineered protein with a thiol-reactive") or quenchable without destroying a sample to which the plurality of analyte detection agents is applied (para [0288]; “quenching of fluorescence"; para [0218]; "the intensity of the signal generated can be tuned over a range extending from the limit of self-quenching to the intensity of a single signal generating moiety").
As to claims 11 and 12, Schwartz discloses a method for detecting one or more biological targets of a sample in a detection assay, comprising: providing a molecular probe, comprising a binding moiety and an oligonucleotide sequence, to a sample comprising one or more biological targets; binding the one or more biological targets with the binding moiety; providing a detectable component to the sample, wherein the detectable component comprises a signal generating moiety conjugated to an oligonucleotide sequence complementary to the oligonucleotide sequence of the molecular probe; hybridizing the oligonucleotide sequence of the target-bound molecular probe to the detectable component; and detecting a signal generated from the hybridized detectable component.(abstract). Multiplexed assays are increasingly common in flow cytometry, where as many as sixteen different analytes may be detected simultaneously or substantially simultaneously. This creates a need for antibodies labeled in a wide range of colors (i.e., at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or more).).[0292].
As to claim 2, Schwartz further discloses that at least one labile tag comprises a fluorophore (para [0184]; “For example, a signal generating moiety may be a fluorophore. Fluorescence generally refers to the physical process in which light is emitted from the compound after a short interval following absorption of radiation").
As to claim 3, Schwartz further discloses that at least one of the plurality of analyte detection agents comprises an oligonucleotide (para [0093); "FIG. 54: is a schematic representation of the process of preassembly using pairs of complementary oligonucleotides in which a plurality of molecular probes and a plurality of detectable components are hybridized, i.e., preassembled, to form a plurality of
preassembled molecular probe-detectable component hybrids, prior to contacting with a sample comprising one or more molecular targets", see sheet 56 fig 54).
As to claim 5, Schwartz further discloses that the oligonucleotide comprises a fluorescent label (para (0184]).
As to claim 6, Schwartz further discloses at least one labile tag is removable with a beta-mercaptoethanol (para [0022]; "In certain embodiments, the conjugate may be formed with a covalent linkage. The covalent linkage may be selected from ... a disulfide"; para [0056]; “a conjugate between an oligonucleotide and a cysteine-containing engineered protein, formed by reacting a cysteine-containing
engineered protein with a thiol-reactive").
As to claim 7, Schwartz further discloses at least one labile tag is quenchable (para [0288]; "quenching of fluorescence"; para [0218]; “the intensity of the signal generated can be tuned over a range extending from the limit of self-quenching to the intensity of a single signal generating moiety").
As to claim 8, Schwartz further discloses that at least one of the analyte detection agents further comprises a linker (para [0020]; "In certain aspects, the modified biomolecules, for example, the modified antibodies, modified proteins, or modified peptides may be prepared by attaching at least one moiety comprising a reactive linker capable of conjugating to a modified oligonucleotide. This at least one moiety
may be attached by a covalent bond. The modified biomolecules may further comprise a molecular tag. Furthermore, the at least one moiety may comprise a spacer group, for example, a polymerized ethylene oxide, such as PEG or PEO").
As to claim 9, Schwartz further discloses that at least one of the plurality of analyte detection agents comprises a cross-linker (para [0156]; “antibody-biotin conjugate, wherein the biotin is further bound to a Streptavidin-oligonucleotide conjugate").
As to claim 13, Schwartz further discloses comprising placing the sample on a planar surface (see for example [0088] FIG. 49: is a schematic representing steps in an antibody-oligonucleotide directed ELISA or planar array protocol wherein (A) an oligonucleotide is immobilized (e.g., on a 96-well plate or planar array surface)).
As to claim 14, Schwartz further discloses an automated system may be able to perform a series of preassembly steps, to create a panel of multiplexed sets that perform a defined or adaptive sequence of tests to characterize a sample; the sample can be placed on a planar surface; a plurality of molecular probes, such as 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 25 or more, 100 or more, 1,000 or more, or 10,000 or more molecular probes, may be placed into individual containers or wells that may then be addressed individually by a robotic [0225].
As to claim 15, Schwartz further discloses and detecting a signal generated from the hybridized detectable component (abstract, [0162]).
As to claim 16, Schwartz discloses removing the signal by treating the sample with a cleavable reagents that targets a label linkage on the tag (para [0022]; "In certain embodiments, the conjugate may be formed with a covalent linkage. The covalent linkage may be selected from ... a disulfide"; para [0056]; "a conjugate between an oligonucleotide and a cysteine-containing engineered protein, formed by reacting a cysteine-containing engineered protein with a thiol-reactive").
As to claim 17, Schwartz further discloses at least one labile tag is quenchable (para [0288]; "quenching of fluorescence"; para [0218]; “the intensity of the signal generated can be tuned over a range extending from the limit of self-quenching to the intensity of a single signal generating moiety").
As per claim 18, Schwartz discloses comprising adding a cross-linking agent to the planar surface ((para [0156]; “antibody-biotin conjugate, wherein the biotin is further bound to a Streptavidin-oligonucleotide conjugate"; para [1219]; A method of bead crosslinking or agglutination, comprising: i) hybridizing a plurality of antibody-oligonucleotide conjugates with a plurality of bead-complementary oligonucleotide conjugates to form a plurality of hybridized antibody-bead conjugates; ii) introducing the plurality of hybridized antibody-bead conjugates to a sample comprising one or more targets; iii) binding at least one target of the one or more targets with at least one hybridized antibody-bead conjugate of the plurality of hybridized antibody-bead conjugates; iv) forming a crosslinking or agglutination of the at least one target-bound hybridized antibody-bead conjugate; and v) analyzing the agglutination to detect, measure, and/or quantify the presence or amount of the at least one target by at least one of the following: a) visual inspection; and b) decreased absorption).
As to claim 20, Schwartz discloses detecting at least 15 different signals form 15 different analytes ((abstract); a method for detecting one or more biological targets of a sample in a detection assay, comprising: providing a molecular probe, comprising a binding moiety and an oligonucleotide sequence, to a sample comprising one or more biological targets; binding the one or more biological targets with the binding moiety; providing a detectable component to the sample, wherein the detectable component comprises a signal generating moiety conjugated to an oligonucleotide sequence complementary to the oligonucleotide sequence of the molecular probe; hydridizing the oligonucleotide sequence of the target-bound molecular probe to the detectable component; and detecting a signal generated from the hydridized detectable component).( para [0292]; Multiplexed assays are increasingly common in flow cytometry, where as many as sixteen different analytes may be detected simultaneously or substantially simultaneously. This creates a need for antibodies labeled in a wide range of colors (i.e., at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or more)).
As to claim 23 Schwartz discloses application of an electric field to remove the signal (para [0150]; The term "signal generating moiety" may refer to a molecule which may be detected directly or indirectly so as to reveal the presence of a target in the sample…for example…a electrochemiluminescent label).
As to claim 24 Schwartz discloses removing the labile tags using a specific restriction enzyme (para [0150]; The term "signal generating moiety" may refer to a molecule which may be detected directly or indirectly so as to reveal the presence of a target in the sample…for example… an enzyme; an enzyme that catalyzes a color change in a substrate; an enzyme substrate; an antibody; an antibody fragment; an antigen; or combinations or derivatives thereof).
Schwartz does not specifically disclose “allows for further analysis of the sample with a second plurality of analyte detection agents”. However, based on the multiplex method disclosure of Schwartz, as already indicated in para [0093], sheet 56 fig 54, and in para [0264], and para [0292], for example, it would have been obvious that the plurality of detection agents disclosed by Schwartz could have been split into a first and second plurality of different detection agents, and used in a sequential manner.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEZIA RILEY/Primary Examiner, Art Unit 1681 28 September 2026
