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 amendments filed 13/3/2025 is acknowledged. In the amendment., new claims 23-25 have been added. New claims 23 and 24, being directed to a method of detection, if presented earlier before the restriction requirement of 05/06/2025, would have been included in Group II invention and thus are withdrawn from consideration as being directed to non-elected invention. Claim 25, being directed elected Group I, is being considered in Group I invention. Therefore, claims 13-22 and 25 are examined on merits in this office action.
Claim Objections
Claim 13 is objected to because the phrase “synthetic biologically molecule” is incorrect. The proper recitation should be “synthetic biological molecule”. Accordingly, correction of the terminology is warranted.
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 13-22 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 13 recites “random copolymer comprising: from 0.5 to 20 mol% of repeating units having a pendant group, which is negatively charged group selected from the group consisting of phophonate, sulfonate and carboxylate; ……………..from 0 to 5 mol% of repeating units having a pendant group, which is a reactive group able to chemically react with a corresponding reactive function of a natural or synthetic biologically molecule”. Since the reactive group able to chemically react with the corresponding reactive function of a natural or synthetic biological molecule, has not been clearly defined in the claim, it is unclear how is the negatively charged carboxylate group recited for “negatively charged group” different from the “reactive group able to chemically react with the corresponding reactive function” ? “Reactive group able to chemically react with corresponding reactive function” reads on carboxylate group as carboxylate group is able to chemically react with corresponding reactive amine function of a natural or synthetic biologically molecule. Thus, as claimed, both the negatively charged group and the reactive group can be the same unit having the pendant group and, in that situation, the different recited mol% would not be as recited in the claim. Moreover, since the corresponding reactive function of the natural or synthetic biologically molecules has not been clearly defined in the claim, the nature of the reactive group is vague and indefinite.
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 of this title, 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 13-16, 19-22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (WO2017/015150A1) in view of Baggerman et al (Langmuir 2019).
Claim 13 is directed to a luminescent polymeric nanoparticle comprising at least one luminescent dye and at least one random copolymer comprising: 1) repeating units having a negatively charged group selected from phosphonate, sulfonate and carboxylate, 2) repeating units having a zwitterionic pendant group, 3) repeating units having a reactive group, and 4) repeating units having a hydrophobic group, wherein each of the repeating groups are of different mol%.
In regards to claims 13, 20 and 25, Zhu discloses a composite (claims 1, 18) comprising a core comprising quantum dots which fall under the definition luminescent dye, and a zwitterionic polymeric coating. The core is a luminescent nanoparticle (claims 5-14). The zwitterionic polymer of Zhu is further defined in claim 4
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which comprises:
-repeating units having a pendant group, which is a negatively charged group chosen from sultanate and carboxylate,
-repeating units having a pendant group, which is a zwitterionic group,
-repeating units having a pendant group, which is a hydrophobic group, and
-repeating units having pendant group, which is a reactive group (carboxylic group is also considered a reactive group).
Zhu also teaches that the zwitterionic polymeric coating facilitate solubility and bioconjugation.
The nanoparticles of claims 13, 20 and 25 differ from Zhu’s nanoparticles in that it comprises a reactive group able to chemically react with corresponding reactive function of a natural of synthetic biological molecule and differ in a selection of a range of mol% of monomers.
Baggerman teaches coating of particles including colloidal gold particle (i.e. luminescent particle) with random co-polymer having reactive group and zwitterionic group to provide antifouling surfaces suitable for bioconjugation (Abstract). Throughout the reference, Baggerman discloses various monomeric units having reactive groups such as azide, alkyne and NHS groups, zwitterionic group, carboxylate group, and sulfonate group (
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) for providing various random co-polymers.
As for example, Baggerman discloses copolymer with zwitterionic group, reactive group and hydrophobic group as disclosed below:
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(Fig.6) conjugated to biological molecules. Baggerman teaches that the ratio of the monomers (various percentages) can be optimized for optimization of antifouling property and biomolecule loading (page 1077, last paragraph of 1st col.).
Therefore, given the teaching of Baggerman of various monomeric groups having various reactive groups, zwitterionic groups, sulfonate group and hydrophobic group for providing zwitterionic co-polymeric compositions for coating particles including luminogenic particles, as for example, gold particles with antifouling property and activated reactive group useful for bioconjugation and optimization with the various monomeric composition, it would be obvious to one of ordinary skilled in the art to easily envisage providing Zhu with the polymeric composition of Beggerman with the expectation of expanding the arsenal of polymeric composition of Zhu for providing reactive surface for bioconjugation with antifouling property with a reasonable expectation of success. Since Baggerman teaches that the ratio of the monomers (various percentages) can be optimized for optimization of antifouling property and biomolecule loading and since Zhu teaches that the molar ratio of the functional groups of the zwitterionic polymer coating (e.g. carboxybetaine groups, sulfobetaine groups, pH responsive groups and thiol containing groups) can be modified to provide desired reactivity of the polymeric coating and the core (page 11, lines 6-9), different mole% of monomer units as claimed would be obvious to one of ordinary skilled in the art depending on desired reactivity and desired nanoparticle sizes and antifouling property absent showing of unexpected advantages with a particular mole percentage composition. Moreover, as evidenced from the claimed wide range of mole% of the various repeat units (0.5 to 20 mol%, 3-30 mol% and 0-5 mol%, note that reactive group can be absent with the 0-5 mol%), a particular mol% composition has not been described as critical to the practice of the invention. Moreover, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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 Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In regards to claim 14, Baggerman teaches methacrylate and methacrylamide based polymer.
In regards to claim 15, as disclosed above in the zwitterion polymer structure of Zhu, the polymer comprises aminocarboxylates and aminosulfates and Baggerman discloses aminosulfates, aminocarbonates and aminophosphates monomers for co-polymeric composition.
In regards to claim16, Baggermen teaches methacrylate and methacrylamide monomers having pendant group for providing polymeric composition having zwitterionic group, sulfonate group, carboxylate group and reactive group and combination of Zhu and Baggerman, as described above provides obviousness of the pendant groups. Moreover, as described above, different mole percentages are obvious in view of Zhu and Baggerman absent showing of unexpected advantages with a particular mole parcentage.
In regards to claims 19, Zhu teaches various particle sizes including 1-10nm, 50-60nm and 60nm (page 15, lines 1-3; page 36, lines 3-5), which is within the range and also overlaps with the claimed ranges and thus are obvious in view of the disclosed ranges. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of “50 to 100 Angstroms” considered prima facie obvious in view of prior art reference teaching that “for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms].” The court stated that “by stating that suitable protection’ is provided if the protective layer is about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.”).
In regards to claim 21, as described above, Zhu teaches natural or synthetic biologically interesting molecule, which is covalently bound to said polymeric chain. Zhu teaches biomolecules selected from chlorotoxin (which is a toxin), avidin (which is a peptide (claims 29-30) and Baggerman discloses biomolecules such as antibody, biotin and concanavalin A conjugated to the polymer (Figs. 4, 5 & 6).
In regards to claim 22, the recitation “for use as a contrast agent, diagnostic agent or a medical imaging agent” is considered as an intended process utilizing the luminescent particle of claim 20, which claim 20 has been shown as obvious in view of the disclosure of Zhu. An intended use that merely states the purpose of the claimed subject matter, without adding additional structure to it, is generally not treated as limiting the scope of the claim. See Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003); Rowe v. Dror, 112 F.3d 473,478 (Fed. Cir. 1997). Moreover, Shu discloses the luminescent nanoparticle for use as an imaging agent (claims 44-45).
In regards to claim 25, as described above, Baggerman discloses various reactive groups including NHS-ester, azide and alkyne as disclosed above.
Claims 13-22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (WO2017/015150A1) in view of Baggerman et al (Langmuir 2019) as described for claims 13-16, 19-22 and 25 above, and further in view of Lequeux et al (EP 2672269A1).
Zhu has been described above that provides the luminescent polymer nanoparticle obvious in view of the disclosures. Zhu however, does not teach the polymeric nanoparticles comprising a fluorescent dye.
Lequeux is directed to nanocomposite comprising pendant groups having zwitterionic group, functional group and fluorescent dyes (Fig. 14 and scheme 3)
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. Lequeux teaches synthesis of the polymer utilizing acrylamide-based monomer to provide acrylamide-based polymer (paragraph [0126] and [0142]). Lequeux teaches that quantum dots with the synthesized polymeric composition provides versatility and provides stability (paragraphs [[0142] – [0146], [0149]). Lequeux teaches that increased colloidal and intracellular stability of coated quantum dots with the polymer makes the polymer a remarkable ligand for long-term live-cell imaging experiments based on fluorescent nanocrystals (para [0149]).
Therefore, from the description in mind of Lequeux, one of ordinary skilled in the art can easily envisage monomer with fluorescent dyes for the polymer coated particles of Zhu in view of Baggerman with the expectation of providing various fluorescent particle useful for detection with a reasonable expectation of success. Lequeux teaches linking dyes (e.g. fluorescein) to the polymeric composition for coating quantum dots and thus various commonly utilized dyes such as rhodamine or cyanine would be obvious to one of ordinary skilled in the art.
Response to argument
Applicant's arguments and amendments filed 12/03/2025 have been fully considered and are persuasive to overcome the rejection under 35 USC 112 (b) but however, Applicant’s arguments have been 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.
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678