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.
Status of the claims
Applicant’s amendments filed 6/4/2026 is acknowledged and entered. In the amendments, claims 3-5, 7-20 and 22 are cancelled and new claims 23-39 are added. Thus, claims 1, 21 and 23-39 are pending and claim 1 is withdrawn as being directed to non-elected invention. See the office action of 01/05/2026 for the withdrawal of claims 1, 3-5 and 7-20 as being directed to non-elected invention. Therefore, claims 21 and 23-39 are examined on merits in this office action.
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.
Claim 21 and 23-39 is 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.
Claim 21 recites “imager strands hybridized to the barcodes” in step (c). The comprising term in line 2 of the claim allows the steps in any order and thus it is unclear hybridization of imager strand is carrier out with the antibody-barcode conjugates bound to the targets” after what step, step (a) or step (b) because hybridization of the imager strands after step (a) will replace (remove) the blocker strands or the removing of step (b) can be carried out after step (c) as they are not recited as carried out sequentially. Claims 23-39 are rejected based on the claims dependent on the rejected claim 21.
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.
Claim 21 and dependent claims 23-39 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.
Amended claim 21 is directed to a method for detecting two or more targets in a biological sample, comprising: a) contacting a sample with two or more antibody-barcode conjugates, each comprising an antibody capable of binding to a different target and a distinct barcode comprising single-stranded nucleic acid; and a blocker strand hybridized to each distinct barcode; (b) removing the blocker strands from the single-stranded nucleic acid barcode; and (c) detecting the two or more antibody-barcode conjugates bound to the targets using imager strands hybridized to the barcodes.
The length and composition of the blocker strand has not been clearly disclosed in the specification and the independent claim 21 does not recite the property (e.g. cleavage sites and types of cleavage sites including photocleavable sites, enzymatic cleavable sites) of the blocker strands when the newly dependent claims recite different types of cleavages. As claimed in the amended claim, the blocker strands can be anywhere on the barcode strands and can be of any size and can be on any position on the barcode strands.
However, throughout the specification, the only clear description teaches that the blocker strand hybridizes to the barcode over the entire length or hybridizes to the barcode over its entire length and further comprises a 5” or 3” overhang. Moreover, specification teaches that a blocker strand that fully blocked the barcode enhance reducing single as compared to blocker strand that partially blocked the barcode. However, throughout the specification, there is no clear description or clear disclosure of how much or what percentage of blockage is considered partial blockage and what length of the barcode sequence are needed to be considered as partial blockage to have desired reduction of background single. Note that the term “reduced signal” has also not been defined as to what percentage of background signal would be considered as reduced single so that the length of the blocker stand is determined. No such clear description or guidance could be found in the specification.
MPEP § 2163 further states that, for a claimed genus (here, all sizes of blocker nucleic acid sequences and at all position on the barcode), the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus:
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Emphasis added.
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, 23, 28, 38 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (US 2018/0371532).
Chen discloses a method of detecting at least one target in a sample comprises (a) providing at least one target-recognizing antibody bound to a docking strand oligonucleotide; (b) providing a blocker strand that hybridizes to the docking strand over a first region, but not over its full length or the full length of the docking strand; (c) providing an imager strand oligonucleotide that hybridizes to the docking strand oligonucleotide at least in the region of the docking strand that does not hybridize to the blocker strand, wherein the imager strand is labeled with a detectable label; (d) allowing the imager strand to hybridize to the docking strand, displacing the blocker strand; (e) determining whether the target-recognizing antibody has bound to the targe (para [0007])
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. As disclosed in the above figure, the blocker strand is removed and then complete hybridization of the imager strand.
Chen teaches that docking strands are defined as oligonucleotides (e.g. single-stranded DNA) which are attached to targets recognition molecules (e.g. antibody) (para [0020], [0026]) and thus is considered as barcode as it is distinct from a target of interest (see the definition of barcode in the specification, para [0069]). Therefore, Chen discloses at least one target recognizing antibody conjugated to a barcode comprising single-stranded nucleic acid wherein the barcode and a blocker strand hybridized to the barcode. Chen teaches that the imager strand is a single stranded oligonucleotide capable of hybridizing to the docking strand and is labeled with a label such as fluorophore or nanoparticle (paragraph [0008], [0021]) and as described above, imager strand hybridize to the docking strand, displacing the blocker strand and detecting the antibody-barcode conjugate using the detectable label of the imager strand (para [0009]). Displace the blocker strand with the imager strand reads on the step (b) of removing the blocker stands from the single stranded nucleic acid barcode of claim 21.
Chen did not specifically disclose contacting sample with two or more antibody-barcode conjugates having distinct barcodes, but however, Chen teaches at least one target recognizing antibody conjugated to a barcode and “at least” one or more. Moreover, Chen teaches different Docking Strands (of different sequences) to different target-recognizing molecules (e.g., antibodies) (para [0024]) and thus detecting two or more targets utilizing two or more antibody-barcode conjugate, each comprising an antibody capable of binding to different target and a distinct barcode comprising single-stranded nucleic acid is obvious for multiplexing and within the purview of one of ordinary skilled in the art.
In regards to claim 23, as described above, Chen discloses blocker strand comprising single-stranded nucleic acids.
In regards to claim 28, as described above, Chen discloses dissociation of blocker strand from docking strand (barcode) by hybridization of imager strand.
In regards to claim 38, Chen teaches blocker strand hybridizes to the docking strand over the full length of the docking strand (claim 1, the alternative embodiment).
In regards to claim 39, Chen teaches blocker strand is bound to the docking strand such that a toehold domain that is complementary to the imager strand remains unhybridized (para [0033]). Therefore, various length of blocker strand including blocker strand having toehold overhangs would be obvious to one of ordinary skilled in the art.
Response to argument
Applicant's arguments filed 06/04/2026 have been fully considered and are persuasive to overcome the rejections under 35 USC 102 and 35 USC 103 in view of the amendments but the argument is rendered moot in view of the new grounds of rejections as described in this office action that are necessitated by Applicant’s amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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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.
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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