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
Status of the Claims
Claims 1, 7-11, 13-15, 21, 24, 26, 30, 36-37 and 43-47 are pending and the subject of this NON-FINAL Office Action. This is the first action on the merits.
Claim Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1, 7-11, 13-15, 21, 24, 26, 30, 36-37 and 43-47 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 pre-AIA the applicant regards as the invention.
The independent claims require “the first detectable moiety has a FWHM of less than about 200nm,” however, FWHM is never defined. It is unclear what this is.
The independent claims require “conventional dye,” which is a vague and subjective phrase. The specification fails to clearly define “conventional.” Nor would a skilled artisan understand the metes and bounds of “conventional dyes.” Thus, the phrase is indefinite.
Claim 10 recites “anti-specifies” and “anti-species” antibodies. These terms are unknown in the art, nor defined in the specification. It is unclear what these are.
Claim 36 recites “the site in which the detectable moiety is conjugated to another moiety of a detectable conjugate,” which includes multiple antecedent basis issues. First, “the site” lacks antecedent basis. It is unclear which site this is. Second, “the detectable moiety” lacks antecedent basis because there are two. Finally “another moiety” lacks antecedent basis.
Further as to claim 36, it is unclear what is a “detectable conjugate.” A conjugate is generally understood in the biological arts as a connection (either temporary or permanent) between two things (label conjugated or connected to an antibody). Thus, claim 36 reads “the site in which the detectable moiety is conjugated to another moiety of a detectable [connection].” It is unclear how a connection is detectable.
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 –
(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.
Claims 1, 11, 14, 21, 26, 37 and 46 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by YANG (US20170314056).
As to claims 1, 11, 14, 21, 26, 37 and 46, YANG teaches a method of visualizing one or more targets within a biological specimen disposed on a substrate, comprising: (a) labeling a first biomarker with a first detectable moiety, wherein the first detectable moiety has a FWHM of less than about 200nm and an absorbance maximum (Amax) of either less than about 430nm or greater than about 670nm (ir-783/mhi-148 heptamethine cyanine dyes; Fig. 38, para. 0075); and (b) staining the biological specimen disposed on the substrate with at least one conventional dye having one or more peak absorbance wavelengths between about 400nm and about 700nm, wherein the peak absorbance wavelength of the first detectable moiety and the one or more peak absorbance wavelengths of the one or more conventional dyes are separated by at least 20nm (DAPI; id.)
Claims 1, 7-8 11, 13-15, 21, 24, 37, 43 and 47 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by CHOU (US20180246089).
As to claims 1, 7, 11, 13-15, 21, 24, 37, 43 and 47, CHOU teaches a method of visualizing one or more targets within a biological specimen disposed on a substrate, comprising: (a) labeling a first biomarker with a first detectable moiety, wherein the first detectable moiety has a FWHM of less than about 200nm and an absorbance maximum (Amax) of either less than about 430nm or greater than about 670nm (coumarin derivative dyes on primary or secondary antibodies, or nucleic acid probes; paras. 0004, 0202 & 1013-1014, claim 61); and (b) staining the biological specimen disposed on the substrate with at least one conventional dye having one or more peak absorbance wavelengths between about 400nm and about 700nm, wherein the peak absorbance wavelength of the first detectable moiety and the one or more peak absorbance wavelengths of the one or more conventional dyes are separated by at least 20nm (“After immunohistochemical staining of the antigen, the tissue sample may be stained with another dye, e.g., hematoxylin, Hoechst stain and DAPI, to provide contrast and/or identify other features”; para. 0203).
As to claims 8 and 44, another dye option is Fluorescein Isothiocyanate, or FITC (para. 1014).
Claims 1, 7-8 11, 13-15, 21, 24, 37, 43 and 47 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by TSENG (US 20100291584).
As to claims 1, 7, 11, 13-15, 21, 24, 37, 43 and 47, TSENG teaches a method of visualizing one or more targets within a biological specimen disposed on a substrate, comprising: (a) labeling a first biomarker with a first detectable moiety, wherein the first detectable moiety has a FWHM of less than about 200nm and an absorbance maximum (Amax) of either less than about 430nm or greater than about 670nm (cell mixture in the microchip was treated with an antibody cocktail containing Cy7-labeled anti-EFGR, Cy5-labeled anti-pAKT, TRITC-labeled anti-PTEN, and FITC-labeled-pS6, yielding a multi-color stain (DAPI[460], anti-EGFR (Cy7) [760], anti-PTEN (TRITC)[550nm], anti-pAKT (Cy5) [650nm] and anti-pS6 (FITC)[495nm]); para. 0312); and (b) staining the biological specimen disposed on the substrate with at least one conventional dye having one or more peak absorbance wavelengths between about 400nm and about 700nm, wherein the peak absorbance wavelength of the first detectable moiety and the one or more peak absorbance wavelengths of the one or more conventional dyes are separated by at least 20nm (id.)
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.
Claim(s) 8 and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over YANG, CHOU or TSENG, in view of Wikipedia, Staining, available at https://web.archive.org/web/20201105231918/https://en.wikipedia.org/wiki/Staining, 11/05/2020.
The prior art as a whole demonstrates that it would have been obvious to a skilled artisan at the time of filing to substitute familiar cell stains based on the specific application with a reasonable expectation of success.
As explained above, YANG, CHOU and TSENG teach cell stains such as DAPI and H&E. They do not explicitly teach any of the dyes in claims 8 and 44.
However, these were known cell stains chosen based on their particular application. For example, Wikipedia teaches Sudan Black for lipids, Congo red for amyloid, and numerous others correlated to their specific use (see below; “Common biological stains”). A skilled artisan would have been motivated to substitute cell stain dyes in YANG, CHOU and TSENG based on the specific application as explained in Wikipedia.
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In sum, it was obvious to substitute the familiar cell stain dyes of Wikipedia for other cell stain dyes to achieve particular stained cell components with a reasonable expectation of success.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over YANG, CHOU or TSENG, in view of BIENIARZ (US 20170254813).
The prior art as a whole demonstrates that it would have been obvious to a skilled artisan at the time of filing to substitute familiar antibody labeling scheme of claims 9-10 based on the specific application with a reasonable expectation of success.
As explained above, YANG, CHOU and TSENG teach antibody labeling. They do not explicitly teach the click chemistry and tyramide or quinone methide chemistry in claims 9-10.
However, these were known antibody chemistries chosen based on their particular application. For example, BIENIARZ teaches fluorescent-labeled antibodies with “Tyramide Signal Amplification: An enzyme-mediated detection method that utilizes the catalytic activity of a peroxidase (such as horseradish peroxidase) to generate high-density labeling of a target molecule (such as a protein or nucleic acid sequence) in situ” (para. 0144).
TSA typically involves three basic steps: (1) binding of a specific binding member (e.g., an antibody) to the target followed by secondary detection of the specific binding member with a second peroxidase-labeled specific binding member; (2) activation of multiple copies of a labeled tyramide derivative (e.g., a hapten-labeled tyramide) by the peroxidase; and (3) covalent coupling of the resulting highly reactive tyramide radicals to residues (e.g., the phenol moiety of protein tyrosine residues) proximal to the peroxidase-target interaction site, resulting in deposition of haptens proximally (diffusion and reactivity mediated) to the target. In some examples of TSA, more or fewer steps are involved; for example, the TSA method can be repeated sequentially to increase signal. Methods of performing TSA and commercial kits and reagents for performing TSA are available (see, e.g., VENTANA Amplification Kit, Cat. No. 760-080, AmpMap Detection Kit with TSA™, Cat. No. 760-121, Ventana Medical Systems, Tucson, Ariz.; Invitrogen; kit No. T-20911, Invitrogen Corp, Carlsbad, Calif.). In some embodiments, TSA is a component of the provided PTDM. Other enzyme-catalyzed, hapten or signaling linked reactive species can be alternatively used as they may become available. Suitable conditions for TSA as well as reagents and kits for use for tyramide signal amplification are known to a person of ordinary skill in the art (see, e.g., Bobrow et al., J. Immuno. Meth., 125:279-285, 1989)
(id.) BIENIARZ further teaches to use click chemistry (paras. 0170ff, Example 4). A skilled artisan would have been motivated to apply this known antibody labeling scheme to achieve greater signal amplification.
In sum, it was obvious to substitute the familiar antibody labeling scheme of BIENIARZ for other antibody labeling to achieve greater signal amplification with a reasonable expectation of success.
Prior Art
The following prior art also teaches combination of dyes that meet the claims: US 20180273758 (para. 0033); US 20190204330; US 20180155275; IPRP in PCT/EP2021/073738.
Conclusion
No claims are allowed.
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/AARON A PRIEST/Primary Examiner, Art Unit 1681