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 .
Priority
This application is a 371 of PCT/US2020/048666 (08/30/2020)
PCT/US2020/048666 has PRO 62/894,683 (08/30/2019).
Status
Applicant states the following:
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However, the current pending claims appear to be 21, and 34-45.
Rejections not reiterated are withdrawn.
Election/Restrictions
Applicant's election without traverse of Group III, claim 21, in the reply filed on 11/4/2025 is acknowledged. Groups I and II, claims 1-19, are withdrawn.
Information Disclosure
An IDS was not filed in this application. Applicant is reminded of the duty of disclosure as per 37 CFR 1.56 and detailed in MPEP § 2000.
New Claim Rejections - 35 USC § 112
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.
Claims 21, 34-45 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
Applicant amended claim 21 to add new language of “adapted to be covalently attached to the surface” and “covalently” while stating support for the added claim limitation is found:
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First, the specification as filed does not have paragraph number as used by Applicant, so the PGPUB numbering is presumed. Second, none of the cited locations provide support for the new claim term covalently attached. In addition, based on the original disclosure one of skill in the art would not recognize that Applicant possessed such a scope of adapted to be covalently attached.
As per MPEP 2163 II A: With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04 ("If applicant amends the claims and points out where and/or how the originally filed disclosure supports the amendment(s), and the examiner finds that the disclosure does not reasonably convey that the inventor had possession of the subject matter of the amendment at the time of the filing of the application, the examiner has the initial burden of presenting evidence or reasoning to explain why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims."). The inquiry into whether the description requirement is met is a question of fact that must be determined on a case-by-case basis. AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1297, 111 USPQ2d 1780, 1788 (Fed. Cir. 2014) ("Whether a patent claim is supported by an adequate written description is a question of fact."); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) ("Precisely how close [to the claimed invention] the description must come to comply with Sec. 112 must be left to case-by-case development."); In re Wertheim, 541 F.2d at 262, 191 USPQ at 96 (inquiry is primarily factual and depends on the nature of the invention and the amount of knowledge imparted to those skilled in the art by the disclosure).
The examiner could not locate support for such a new limitation, nor does there appear to be a written description of the limitation in the application as filed. See Hyatt v. Dudas, 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that "[MPEP] § 2163.04 (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection."). There is no literal support for the added limitation and one of skill in the art would not recognize that Applicant possessed the claim scope. Thus, claim 21 and those that depend therefrom are rejected.
New Claim Rejections - 35 USC § 103
Claim 21, 34-45 are rejected under 35 U.S.C. 103 as being unpatentable over Trau et al. (US7338768) in view of Rogers et al. (US20060286488), Auer et al. (WO2009000775), and Pelaz et al. (ACS Nano 2017, 11, 2313−2381).
Regarding Claim 21, Trau teaches a system for preparing a combinatorial library with fluorescent encoding in a combinatorial synthesis (This invention relates generally to carrier-reporter bead assemblies and their use in relation to oligomer libraries which may be formed by
a combinatorial split-process-recombine procedure, Col. 1, Lns. 13-15), the system comprising:
a) providing a set of labelling beads comprised of a plurality of labeling bead types, each labelling bead type being adapted to attach to the surface of a carrier bead or be captured in the bulk of a carrier bead, each labelling bead type having unique fluorescent label which is optically resolvable from the unique fluorescent label of other labelling bead type when attached to the surface of a carrier bead or captured in the bulk of a carrier bead; wherein: the unique fluorescent label on each labelling bead type comprises one, two or more fluorescence emission bands and one, two or more fluorescence excitation bands, each fluorescence emission band being distinguishable by one, two or more of: (i) the representative wavelength of emission, (ii) the intensity of emission, (iii) the characteristic wavelength of the excitation band exciting the
emission, and (iv) the efficiency of excitation in this excitation band exciting the emission; and the unique fluorescent label on each labelling bead type is spectrally distinct from the unique fluorescent label on the other labelling bead types in the set of labelling beads, such that the plurality of labelling bead types, in combination, are each uniquely labelled (“Generally, for a split-process-recombine procedure with m steps and n processes, a set of mxn batches of reporter beads is sufficient to uniquely tag the entire process. In the above example, we showed how 16 unique tags could be produced from a combination of 4 fluorescent dyes. This number can be vastly increased by a number of simple schemes: (I) Increase the number of fluorescent dyes, with distinct fluorescent signals, incorporated inside the reporter particle .... (Ill) The concentration of fluorescent dye within each reporter bead can be varied. Different concentrations will give rise to different emission intensities (e.g., two different dye concentrations within the reporter beads will double the number of possible tags)”, Col. 14, Ln. 65 - Col. 15, Ln. 42; “Carrier-reporter bead assemblies”, Title; claim 1);
b) providing a plurality of carrier beads (“According to one aspect of the invention, there is provided an assembly of a carrier having one or more reporter beads non-covalently attached thereto. … According to yet another aspect of the invention, there is provided a method for forming a synthetic oligomer library comprising a plurality of molecules comprising a multiplicity of different chemical groups, said method including the steps of: ... (i) attaching a respective chemical group to a carrier in each of a plurality of reaction vessels”, Col. 4, Lns. 20-39);
c) providing a set of molecular building blocks for a combinatorial synthesis, the combinatorial synthesis having a plurality of steps, and each step of the combinatorial synthesis having a molecular building block, each building block being the same or different (“(ii) attaching a reporter bead to the carrier in non-covalent manner in each reaction vessel wherein each reporter bead has a marker associated therewith”, Col. 4, Lns. 40-42);
d) performing a sequence of steps of the combinatorial synthesis on a group of carrier beads, the sequence of steps comprising adding a new molecular building block to a group of carrier beads at each step of the combinatorial synthesis to form the combinatorial library, each group of carrier beads in the library having a unique synthetic compound (“(iii) combining the carriers from each reaction vessel resulting from steps (i) and (ii) into a recombination vessel; (iv) splitting the carriers from the recombination vessel into the plurality of reaction vessels wherein steps (i) and (ii) are repeated; and (v) repeating steps (iii) and (iv) until the library of molecules is formed wherein each molecule will have a unique signal associated therewith which signal is dependent on different combinations of markers to facilitate direct identification of the sequence of chemical groups comprising said molecule”, Col. 4, Lns. 43-54);
e) matching each molecular building block bound to the group carrier beads in a given sequence step of the combinatorial synthesis with a labelling bead type, thereby forming a population of different carrier bead groups, each carrier bead group having a unique synthetic molecule and corresponding unique fluorescent label encoded on the carrier bead, the unique fluorescent label being produced by the plurality of different labelling bead types, each with unique fluorescent labels, attached to the surface of the carrier beads in consecutive steps of the combinatorial synthesis (“Carriers tagged with red and blue reporters correspond to the peptide sequence Arginine-Glycine-carrier; carriers tagged with green and blue correspond to the sequence Arginine-Alanine-carrier; carriers tagged with green and yellow/red correspond to the sequence Lysine-Alanine-carrier and carriers tagged with red and yellow/red reporters correspond to the peptide sequence Lysine-Glycine-carrier”, Col. 19, Ln. 65 - Col. 20, Ln. 4);
f) identifying the labelling bead types attached to each carrier bead by an optical interrogation technique, wherein the unique fluorescent label on at least one labelling bead type is identifiable with an optical interrogation technique, and wherein the carrier beads are optically interrogated and the diameter of the smallest optically resolved region is smaller than the diameter of the carrier beads (“The invention in another aspect also includes a process of decoding molecules which are encoded by the process of the invention which includes the step of analysis of the reporter beads as described hereinafter so as to determine the unique sequence of the chemical groups which comprise each of the molecules”, Col. 7, Lns. 17-22).
Regarding amended claim 21 with the new language of “each labelling bead type being adapted to be covalently attached to the surface” and “when covalently attached”, Trau teaches that the prior art describes covalent bonding as a means of attachment of beads and provides and example with covalent attachments (col. 10, Example 10: “Once reporter bead attachment to carriers has been induced through manipulation of colloidal forces, the robustness of attachment may be strengthened through the formation of Supplementary covalent bonds between Surface groups of the two colloids. For example, a peptide bond”; claims 1, 11: “a carrier particle having a plurality of distinguishable colloidal reporter particles … wherein each colloidal reported particle … is suitable for covalent attachment of at least one chemical group”, “wherein a chemical group is covalently attached to said carrier particle.”).
Regarding claim 21’s new language of “wherein the optical interrogation technique is confocal fluorescence spectroscopy or confocal fluorescence imaging” Trau does not specifically teach the techniques.
Although Trau teaches identifying the beads by fluorescence optical microscopy (Col. 10, lines 52-54), Trau does not explicitly disclose optically interrogation with three-dimensional (3D) resolution.
Rogers teaches using a 3D resolution optical interrogation technique to measure the diameter of beads ([0006]: “The present invention provides methods, devices and device components for fabricating 3D structures and patterns of 3D structures”; [0110]: “The series of images collected with a confocal microscope reveals the full 3D shape of this polymer nanostructure”; [0112]: “For the structures in FIGS. 7A-L, the finest features (i.e. post diameters, line widths; see red arrow) have dimensions of ~100 nm; and in certain cases features as small as 50 nm may be achieved”).
Auer teaches screening labeling of beads using covalently attached probes with confocal fluorescence spectroscopy (p. 17, 27).
Pelaz reviews bead detection techniques including use of QDs (quantum dots) with fluorescent confocal imaging (Fig. 10).
One of ordinary skill in the art would have considered in constructing Trau’s particles such that the resulting particles would be adapted to be covalently attached in the same manner as in the instant claims to improve detection through the combined use of reporter beads with carrier beads. One of ordinary skill in the art would have been further motivated by Auer and Pelaz’s successful detections using covalently attached beads and QDs which were well-known in the art.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Trau with the teaching of Rogers for the purpose of using 3D-resolution techniques such as confocal microscopy to determine the 3D properties of beads such as their diameter to assess their suitability for use as carrier beads of labeled beads.
Regarding claim 34, as with claim 21, one of ordinary skill in the art following the combined teaching of Trau in view of the secondary references would have considered improving detection by combining beads with unique labels for detection in the same manner as in the instant claims.
Regarding claims 35-37, Trau in view of the secondary references teach the same well-known techniques.
Regarding claim 38, Trau teaches the label/tag are distinguishable by differential absorption/emission of light.
Regarding claims 39, Pelaz teaches the use of QDs which was a well-known technique for detection that one of ordinary skill in the art would have used.
Regarding claims 40-41, 44-45, one of ordinary skill in the art would have considered optimization of the size and shapes of the beads as was routine in the art. MPEP 2144.04 IV.
Regarding claims 42-43, Trau teaches distinguishing tags on beads by their optical properties (“the identifier tag is described in very broad terms, such as any recognizable feature, which includes a microscopically distinguishable shape, size, colour or optical density; a differential absorbance or emission of light;”).
The level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that Trau teaches beads are coagulated or non-covalently attached on the carrier while the instant claims are to bead covalently attached to carrier beads.
This argument is not persuasive because Trau does teach covalent attachment of beads (col. 10, Example 10: “Once reporter bead attachment to carriers has been induced through manipulation of colloidal forces, the robustness of attachment may be strengthened through the formation of Supplementary covalent bonds between Surface groups of the two colloids. For example, a peptide bond”; claims 1, 11: “a carrier particle having a plurality of distinguishable colloidal reporter particles … wherein each colloidal reported particle … is suitable for covalent attachment of at least one chemical group”, “wherein a chemical group is covalently attached to said carrier particle.”), which one of ordinary skill in the art would have considered in constructing Trau’s particles such that the resulting particles would be adapted to be covalently attached in the same manner as in the instant claims. Furthermore, Auer and Pelaz both teach covalent attachments of equivalent reporter particles demonstrating that such a configuration was well-known. In addition, one of ordinary skill in the art would have reasonably considered utilizing covalent bonds for attachment as an alternative to Trau’s non-covalent attachment because Trau teaches both and because such means of attachment were well-known in the art and would have been routine for one of ordinary skill in the art to implement to achieve the same result.
Applicant argues that Trau does not disclose a mathematical estimate of the depth of the encoding; the diversity of the labelling beads and that quantum dots and confocal fluorescence imaging/spectroscopy “did not exist at the time Trau’s application was filed”; and thus the skilled artisan could not reasonably envision the claimed invention.
This argument is not persuasive because 1) the instant claims do not specifically require “a mathematical estimate” as alleged; 2) the time of Trau’s application filing is not the legal standard for consideration – 35 USC 103’s relevant inquiry is before the effective filing date of the instant application; 3) quantum dots and confocal fluorescence imaging/spectroscopy did exists before the effective filing date of the instant application and one of ordinary skill in the art would have considered their use as evidenced by Auer and Pelaz.
Applicant argues that Rogers is unrelated to Trau and thus would not reasonably lead one of ordinary skill in the art to the present invention.
This argument is not persuasive because one of ordinary skill in the art would have considered Rogers as it teaches imaging of nanoscale beads which is precisely related to Trau’s nanoparticle beads.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joseph McKane can be reached at 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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