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
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.
Response to Election/Restrictions
Applicant’s election without traverse of Group II (claim 21) is acknowledged. Claim 22 was intended to include in Group II but was inadvertently omitted from the election/restriction requirement sent on 06/13/2025. Therefore, claim 22 is included in the elected Group II, thus Group II includes claims 21 and 22.
Therefore, claims 1, 3-5 and 7-20 are withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Applicants preserve their right to file a divisional on the non-elected subject matter.
Claims 21 and 22 are examined on merits in this office action.
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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 22 is rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Nadeau et al (US 2015/0152473).
Nadeau teaches a method of detection of two targets in a biological sample utilizing two analyte specific binding entities (proximity pair) such as antibodies that binds to two different epitopes on the same analyte or different analytes in close proximity (para [0007]). Nadeau teaches that each analyte specific binding entity (e.g. antibody) is conjugated to a single-stranded nucleic acid (an oligonucleotide moiety; i.e. a barcode) (para [0007]) wherein the single-stranded nucleic acid (barcode) when in close proximity, partially hybridize to each other, thus each barcode is distinct (having different sequence) (Figs. 1G, 1J). Nadeau teaches providing one or more hybridization blocker oligonucleotides (hybridization blocker) which hybridizes with the oligonucleotide moieties of the proximity member (para [0008]). Nadeau teaches a detection of two or more targets in a biological sample, comprising:
a) contacting the sample with first and second proximity member (i.e. antibody) having the oligonucleotide moieties (i.e. barcodes) in a reacting mixture, wherein the oligonucleotide moieties (i.e. the barcodes) are hybridized to the hybridization blocker (i.e. a barcode precursor comprising a double-stranded nucleic region comprising a distinct barcode hybridized to a segment of a blocker strand); b) dissociating the hybridization blocker from the barcode oligonucleotides (i.e. removing the blocker strands from the barcode precursors to form single-stranded barcodes); and c) allowing amplicon to form between the analyte-bound proximity pair (para [0008]) and detecting the antibody-barcode conjugates bound to the target by detecting amplicon dependent amplification product using the barcode (para [0095] and claims 1, 20 and 24). Therefore, the reference is deemed to anticipate the cited claim.
Claim Rejections - 35 USC § 103
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.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Giedt et al (Nature communications 2018).
In regards to claims 21 and 22, Giedt teaches detection of two or more targets by contacting the sample with two or more antibody-barcode conjugates wherein each antibody-barcode conjugate comprises an antibody capable of binding to different target (see Fig.2: mAb-DNA conjugates against EGFR and pS6) and a barcode wherein the barcode is hybridized with a blocker strand (
PNG
media_image1.png
153
240
media_image1.png
Greyscale
, mAb-DNA-Fl: Fig. 1). Giedt teaches detecting the antibody-barcode conjugates (mAb-DNA-Fl) bound to the target and removing the blocker strand having the fluorophores by washing in deionized water (page 2, lines 27-34 of 2nd col.).
Giedt does not disclose that the barcode of each antibody-barcode conjugate is distinct, but however, Giedt teaches that mAb–DNA-Fl conjugates containing different fluorochromes for each mAb in each imaging cycle (page 2, lines 27-34 of 2nd col.) wherein the blocker strand comprises complementary oligo with two linked fluorochromes (Fig.1;
PNG
media_image2.png
58
163
media_image2.png
Greyscale
). Therefore, from the description in mind, one of ordinary skilled in the art can easily envisage distinct barcode for each antibody-DNA-Fl conjugates with various complementary oligo with various fluorochromes with a reasonable expectation of success.
Claims 21 and 22 is rejected under 35 U.S.C. 103 as being unpatentable over Nadeau et al (US 2015/0152473) as described above for claim 22 and further in view of Xlaochum et al (WO 2011/022820A1).
Nadeau has been cited above anticipating claim 22. Nadeau teaches a method of detection of two targets in a biological sample utilizing two analyte specific binding entities (proximity pair) such as antibodies that binds to two different epitopes on the same analyte or different analytes in close proximity (para [0007]). Nadeau teaches that each analyte specific binding entity (e.g. antibody) is conjugated to a single-stranded nucleic acid (an oligonucleotide moiety; i.e. a barcode) (para [0007]) wherein the single-stranded nucleic acid (barcode) when in close proximity, partially hybridize to each other, thus each barcode is distinct (having different sequence) (Figs. 1G, 1J). Nadeau teaches providing one or more hybridization blocker oligonucleotides (hybridization blocker) which hybridizes with the oligonucleotide moieties of the proximity member (para [0008]). Nadeau teaches a detection of two or more targets in a biological sample, comprising:
a) contacting the sample with first and second proximity member (i.e. antibody) having the oligonucleotide moieties (i.e. barcodes) in a reacting mixture, wherein the oligonucleotide moieties (i.e. the barcodes) are hybridized to the hybridization blocker; b) dissociating the hybridization blocker from the barcode oligonucleotides; and c) allowing amplicon to form between the analyte-bound proximity pair (para [0008]) and detecting the antibody-barcode conjugates bound to the target by detecting amplicon dependent amplification product using the barcode (para [0095] and claims 1, 20 and 24).
Nadeau discloses blocker strand hybridized to barcode but does not specifically mention that the blocker strand hybridizes to the barcode over the entire length or the blocker strand hybridizes to the barcode over the entire length and further comprises a 5’ or 3’ toehold overhang. However, Nadeau discloses blocker blocking various regions of the barcode and also having 5’ or 3’ overhang (Fig. 4EE, Fig. 4G, 4I 11A) to reduce non-specific interactions and improve sensitivity (para [0008] & [0108]).
Xlaochum teaches proximity assay utilizing first targeting molecule having an first oligonucloetide having a free end and a second targeting molecule having a second oligonucleotide having a free end, wherein the first oligonucleotide is complementary to the second oligonucleotide, wherein upon binding of the targeting molecule to the target molecule, the free end of the oligonucleotide hybridizes at or near the free end of the oligonucleotides (abstract). Xlaochum teaches utilizing blocking oligonucleotides to block the free end of the first and second oligonucleotides to improve background signal. Xlaochum teaches that the blocking agent may comprise a blocking oligonucleotide that may hybridize in whole or in part to the portion of the oligonucleotide of the first probe that is complementary to that of the second probe. In another embodiment, the blocking agent may comprise a blocking oligonucleotide that may hybridize in whole or in part to the portion of the oligonucleotide of the second probe that is complementary to that of the first probe. In a further embodiment, the blocking agent may comprise a blocking oligonucleotide that may hybridize in whole or in part to the portion of the oligonucleotide of the first probe that is complementary to that of the second probe; and a blocking oligonucleotide that may hybridize in whole or in part to the portion of the oligonucleotide of the second probe that is complementary to that of the first probe. Xlaochum teaches that a blocking oligonucleotide may be of any composition and length that is suitable for use in reducing and/or preventing background hybridization of the probes. A skilled person would appreciate that the blocking agent may reversibly block the hybridization of the probes. A blocking agent of the invention is not permanently attached to a probe (i.e. by cross-linking or covalent bond), and thus blocking of a probe may be reversed. For example, a blocking agent may be a blocking oligonucleotide that hybridizes to a probe. The blocking oligonucleotide may dissociate from the probe due to conditions, such as, elevated temperatures and/or through random motion (i.e. association/disassociation) of molecules (pages 22-23).
Therefore, given the teaching of Xlaochum that blocking oligonucleotide improves background signals and that a blocking oligonucleotide that may hybridize in whole or in part to the portion of the oligonucleotide of the first probe that is complementary to that of the second probe and given the fact that Nadeau provides the basic concept of providing blocker strand for hybridizing to barcode for reducing non-specific interaction and improving sensitivity, one of ordinary skilled in the art can easily envisage different variations of blockers hybridizing to various regions of the barcode including blocking the entire region of barcode for optimization depending on the detection process of the barcode because discovering the optimum or workable ranges involves only routine skill in the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHAFIQUL HAQ whose telephone number is (571)272-6103. The examiner can normally be reached on Mon-Fri 8-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached on 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678