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 1-20 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.
Claim 1 is vague and indefinite because it is missing a purpose that goes beyond mere detection of analytes. However, according to the description the purpose
appears to be the reduction of photodamage. Other essential features are also
missing from the claims. In claim 1 the source of photons, the nature of
interaction with the complex and their readout is missing. The relation of the
signal to the other elements is undefined. Furthermore, essential elements for achieving single molecule readout are missing. The macromolecules also lack the properties required for their specific interaction. For example, it is unclear how the analytes of interest are specifically and in an individualized form bound to the array sites (Claims 1 and 20). The step of coupling photodamage inhibitor moieties to the complex in claim 1 appears to take place after the detection. It is thus unclear when the complex is labelled, and it is also unclear how specific labelling of the complex is achieved.
Claims 14-16 are vague and indefinite because it is unclear what exactly is an avidity component.
Claim 18 is vague and indefinite because it is unclear what exactly is the fluidic medium and how the detection is performed with said fluidic medium.
Note that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. Also see In re Van Geuns, 988 F.2d 1181,26 USPQ2d 1057 (Fed. Cir. 1993). Also see, In re Zetz, 13 USPQ2d 1320,1322. “An essential purpose of patent examination is to fashion claims that are precise, clear, correct and unambiguous.”
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 1-20 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The description provides mere lists of possible assay configurations, while the examples only provide known photo inhibitors and their chemistry and generic coupling reactions instead of the claimed method. In order to achieve the desired reduction of photodamage for a selected analyte the skilled person would have to embark on a research mission without any teaching in the application of how to achieve it for the particular analyte and assay configuration, which amounts to an undue burden. Furthermore, it is known that excess of photo protective agents can interfere with small volume assays (EP 2252625: §20). Also, in the case where the photodamage inhibitors are enzymatic systems (see specification §183) it is highly likely that a site with 100 or more photodamage inhibitors (claim 20) will not result in an
improved detection of the single molecule due to sterical reasons.
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) 1-9, 11-20 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 Eid WO 2007/064905.
Eid discloses a composition, comprising: a first reactant, a second reactant, and
a photodamage mitigating agent, wherein interaction of the first reactant with the second reactant under excitation illumination generating a signal causes photodamage to the first reactant in the absence of the photodamage mitigating agent (claims 1, 24, §7-11); Eid discloses the first reactant being immobilized on a surface of an array zero mode waveguide (claims 6-8); Eid provides devices that comprise a substrate having an observation region, a first reactant immobilized within the observation region, a second reactant disposed within the observation region, wherein interaction between the first and second reactants under excitation illumination causes photodamage to the first reactant, and a photodamage mitigating agent disposed within the observation region (§9); Eid discloses photodamage mitigating agents (see claims 14-24); Eid discloses arrays (claim 54, $54, Fig.4-6); Eid discloses single molecule analyses in assays of nucleic acids, enzymes, antibodies (§5, 31); Eid discloses photodamage mitigation agents provided as reaction mixture component or immobilized on the place of the reaction ($47-48); Eid teaches a substrate may comprise any of a variety of formats, from planar substrates, e.g., glass slides or planar surfaces within a larger structure, e.g., a multi-well plates such as 96 well, 384 well and 1536 well plates (this is viewed as claim 20 step c) wherein the fraction of sites contains an average of at least 100 photodamage inhibitor moieties per site) or regularly spaced micro- or nano-porous substrates, or such substrates may comprise more irregular porous materials, such as membranes, aerogels, fibrous mats, or the like, or they may comprise particulate substrates, e.g., beads, spheres, metal or semiconductor nanoparticles, or the like. In addition, for purposes of discussion herein, whether a particular reagent is confined by virtue of structural barriers to its free movement, or is chemically tethered or immobilized to a surface of a substrate, it will be described as being "confined" ([0042], [0051]; [0070]-[0071]). Eid teaches there are from 1 to 3 molecules of the first reactant immobilized within the first area (viewed as a plurality); Eid teaches the first reactant comprises an enzyme, and the second reactant comprises a fluorescent or fluorogenic substrate for the enzyme (inherently comprising an affinity agent) (see claims).
Eid discloses photodamage mitigating agents may generally be provided as a component of the reaction mixture, either through addition as an additive, either liquid or solid, or through predisposition and/or immobilization of the photodamage mitigating agents within the region where the reaction is taking place. By way of example, in cases where the reaction of interest is confined to a particular region or location, it may be desirable to immobilize or otherwise localize the photodamage mitigating agents within or proximal to that region. Likewise, where photodamage mitigating agent comprises cooperatively functioning components, e.g., dual enzyme systems, it may again be desirable to localize such components relative to each other, as well as to the reaction of interest [0047]; Eid discloses a device, comprising: a substrate having an observation region; a first reactant immobilized within the observation region; a second reactant disposed within the observation region, wherein interaction between the first and second reactants under excitation illumination causes photodamage to the first reactant; and photodamage mitigating agent disposed within the observation region (claim 33). (this is viewed to be inclusive of claims 11-16).
The embodiments set forth in claims 17-19 are merely some of the several straightforward possibilities which the skilled person would select, in accordance with circumstances, without requiring any inventive skill in order to solve the problem posed. One of ordinary skill in the art would have been motivated to modify the primary references in the manner of the claims to achieve the expected benefits, optimizations and/or expanded applications as this is well known practice in the art. MPEP states wherein the “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Alter, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Routine optimization is not considered inventive, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, an ordinary practitioner would have recognized that the method could be adjusted to maximize the desired results.
Claim(s) 1-20 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 Kong et al. (EP 2252625).
Kong et al. teaches compounds, compositions, methods, devices and systems for limiting the effects of photodamage during illuminated reactions, particularly reactions that employ fluorescent or fluorogenic reactants. The term "photodamage" refers generally to any direct or indirect impact of illumination on one or more reagents in a reaction which results in a negative impact upon that reaction. The term "illuminated reactions" as used herein refers to reactions which are exposed to an optical energy source. Typically, such illumination is provided in order to observe the generation and/or consumption of reactants or products that possess a particular optical characteristic
indicative of their presence, such as a shift in the absorbance spectrum and/or emission spectrum of the reaction mixture or its components. Kong et al. provides methods and compositions for nucleic acid analysis in which a nucleoside polyphosphate is linked to a fluorescent dye, and wherein the compound further includes, integrated into its structure, a photoprotective agent. As used herein, the term "photoprotective agent" is used interchangeably with the term "photodamage mitigating agent" and generally refers to any agent that can prevent and/or mitigate damages caused by illumination. In certain exemplary aspects, the dye is linked to the nucleoside polyphosphate by a linker, where the linker itself comprises a photoprotective agent (overview).
Kong et al. discloses photoprotective agents; attachment to a device (claims 1-5, §33-36); single molecule analyses using zero mode waveguide arrays (§3-6, 84-86, 89); single molecule analyses including enzyme analyses, hybridization assays (e.g., antibody assays), nucleic acid hybridization assays subjected to prolonged illumination from relatively concentrated light sources (§22). King et al. teaches the photoprotective agents may be incorporated into compounds in a variety of different ways; a conjugate of the invention is a linear molecule which comprises a dye, a nucleoside polyphosphate, and a photoprotective agent. For example, the photoprotective agent may be incorporated into a linker that connects a dye molecule to a nucleoside polyphosphate. In a further non-limiting example, the linear conjugates can comprise a dye, a photoprotective agent, and a nucleoside polyphosphate in any order (i.e., dye-agent-nucleoside, agent-dye-nucleoside, dye-nucleoside-agent, etc.) (§ 29-30) (this is viewed to be inclusive of claims 11-19). Kong et al. teaches conjugates comprising branched structure (§44). Kong et al. teaches conjugates can be formed using methods known in the art. In a preferred embodiment, linkers are derived from molecules which comprise a reactive functional group on each terminus, and these reactive functional
groups can react with complementary reactive functional groups on the dye and/or the nucleotide (pages 8-9). Kong et al. teaches in preferred aspects, however, such limited quantity reagents or reactants refer to reactants that are immobilized, or otherwise confined within a given area, so as to provide limited quantity of reagents in that given area, and in certain cases, provide small numbers of molecules of such reagents within that given area, e.g., from 1 to 1000 individual molecules [0087] (this is viewed to be inclusive of claim 20).
The embodiments set forth in claims 17-19 are merely some of the several straightforward possibilities which the skilled person would select, in accordance with circumstances, without requiring any inventive skill in order to solve the problem posed. One of ordinary skill in the art would have been motivated to modify the primary references in the manner of the claims to achieve the expected benefits, optimizations and/or expanded applications as this is well known practice in the art. MPEP states wherein the “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Alter, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Routine optimization is not considered inventive, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, an ordinary practitioner would have recognized that the method could be adjusted to maximize the desired results.
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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/JEZIA RILEY/Primary Examiner, Art Unit 1681 26 September 2026
