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 .
Status of Claims
A new claim set was filed on 7/14/26 with the following:
Amended claims
1-2, 8 and 15-16
Newly canceled claims
7, 14 and 21
Newly added claims
Previously canceled claims
Previously withdrawn claims
1-6 and 15-20
Claims under instant examination
8-13
Oath/Declaration
Declaration filed under 37 C.F.R. 1.132 on 7/14/26 has been fully considered but is not found persuasive to overcome the obviousness conclusion of this case (See Response to Arguments for details).
Withdrawn Claim Objections/Rejections
All rejections pertaining to claims 7, 14 and 21 are moot because the claims were cancelled in view of the amendments filed on 7/14/26.
The objections to claim 9 for minor informalities are hereby withdrawn in view of the claim amendments filed on 7/14/26.
The rejections of:
claims 8 under 35 U.S.C. 102(a)(1) as being anticipated by Yoo et al. (Cell Death Dis., 8(8), 8/17/17; in IDS dated 6/20/25)
is hereby withdrawn in view of the claim amendments filed on 7/14/26.
Maintained and Modified Claim Rejections - 35 USC § 103
Applicant' s claim amendments have necessitated the following modified grounds of rejection.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 8 and 10-13 remain rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2013/0045499; published: 2/21/13; of record), in view of Clausen et al. (US 2017/0369905; published: 12/28/17; of record).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Medintz is directed to compact multifunctional ligand to enhance colloidal stability of nanoparticles (e.g., quantum dots) [Title and Abstract].
With regards to instant claims 8 and 10-13, Medintz teaches stable conjugation between quantum dots (QDs) and His-tagged proteins, wherein the QDs are coated with compact ligands (CLs) [0050-0054]. The compact ligand is CL4:
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[See claims and Figures]. Medintz teaches that the QD is a metallic nanoparticle (e.g., Ag, Au, Cu, Pd, Pt) [0015] and specifically, gold nanoparticles [0061].
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Although Medintz teaches a His-tagged protein conjugated to the QD, Medintz does not teach wherein the His-tagged protein is a His-tagged erythropoeitin, as required by instant claims 8 and 13. However, this deficiency is cured by Clausen.
Clausen teaches that the polypeptide erythropoietin (EPO) is a protein involved in hemostasis, including a coagulation factor [0060]. Furthermore, Clausen teaches a His-tagged recombinant human EPO [0500 and 0509].
Medintz does not teach wherein the quantum dot specifically has from 2 to 40 molecules of the human erythropoietin deposited thereon, as required by instant claim 8.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Medintz and Clausen are both directed to the use of biologically active proteins. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the invention was effectively filed, to modify the His-tagged protein conjugated to QDs of Medintz by substituting the His-tagged protein of Medintz with the His-tagged human EPO taught by Clausen to achieve the predictable result of obtaining a composition suitable for providing biological activity when administered to patient. One of ordinary skill in the art would have been motivated to do so because Clausen teach that it is advantageous for hemostasis [0060].
The amount of molecules of the human erythropoietin deposited on the QD is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount protein on the QD in order to best achieve the desired results as such would provide advantageous biological effect. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where 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, 105 USPQ 233 (CCPA 1955). In the instant case, Medintz teaches that conjugation of His-tagged biomolecules onto QD surfaces commonly increases the fluorescence intensity or quantum yield of the QDs; this enhancement is ascribed to better passivation of surface trap states on the QD surface. The Examiner considers it prima facie obvious to optimize the amounts of any biologically active agent to achieve their known biological effect, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amounts of molecules of the human erythropoietin deposited on the QD would impact the fluorescence intensity or quantum yield of the QDs and therefore be an optimizable variable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claims 8-13 remain rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2013/0045499; published: 2/21/13; of record), in view of Clausen et al. (US 2017/0369905; published: 12/28/17; of record) and Fatima et al. (J. Funct. Biomater. 2021, 12, 75; in IDS dated 6/20/25; of record).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Medintz is directed to compact multifunctional ligand to enhance colloidal stability of nanoparticles (e.g., quantum dots) [Title and Abstract].
With regards to instant claims 8 and 10-13, Medintz teaches stable conjugation between quantum dots (QDs) and His-tagged proteins, wherein the QDs are coated with compact ligands (CLs) [0050-0054]. The compact ligand is CL4:
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310
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[See claims and Figures]. Medintz teaches that the QD is a metallic nanoparticle (e.g., Ag, Au, Cu, Pd, Pt) [0015] and specifically, gold nanoparticles [0061].
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Although Medintz teaches a His-tagged protein conjugated to the QD, Medintz does not teach wherein the His-tagged protein is a His-tagged erythropoeitin, as required by instant claims 8 and 13. However, this deficiency is cured by Clausen.
Clausen teaches that the polypeptide erythropoietin (EPO) is a protein involved in hemostasis, including a coagulation factor [0060]. Furthermore, Clausen teaches a His-tagged recombinant human EPO [0500 and 0509].
Although Medintz teaches a His-tagged protein conjugated to the QD, Medintz does not teach wherein the QD comprises a cadmium selenide core; an inner cadmium sulfide shell in contact with the cadmium selenide core; and an outer zinc shell in contact with the inner cadmium sulfide shell, as required by instant claim 9. However, this deficiency is cured by Fatima.
Fatima is directed to quantum dots used to treat cancer [Title]. Fatima teaches a QD comprises a CdSe core, followed by a CdS shell and followed by a ZnS shell [Fig. 2].
Medintz does not teach wherein the quantum dot specifically has from 2 to 40 molecules of the human erythropoietin deposited thereon, as required by instant claim 8.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Medintz and Clausen are both directed to the use of biologically active proteins. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the invention was effectively filed, to modify the His-tagged protein conjugated to QDs of Medintz by substituting the His-tagged protein of Medintz with the His-tagged human EPO taught by Clausen to achieve the predictable result of obtaining a composition suitable for providing biological activity when administered to patient. One of ordinary skill in the art would have been motivated to do so because Clausen teach that it is advantageous for hemostasis [0060].
Based on the teachings of Medintz and Fatima, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (the QD of Medintz with the CdSe/CdS/ZnS QD of Fatima for the purpose of providing a QD that biologically active proteins can be conjugated to) (See MPEP 2144.06-II).
The amount of molecules of the human erythropoietin deposited on the QD is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount protein on the QD in order to best achieve the desired results as such would provide advantageous biological effect. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where 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, 105 USPQ 233 (CCPA 1955). In the instant case, Medintz teaches that conjugation of His-tagged biomolecules onto QD surfaces commonly increases the fluorescence intensity or quantum yield of the QDs; this enhancement is ascribed to better passivation of surface trap states on the QD surface. The Examiner considers it prima facie obvious to optimize the amounts of any biologically active agent to achieve their known biological effect, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amounts of molecules of the human erythropoietin deposited on the QD would impact the fluorescence intensity or quantum yield of the QDs and therefore be an optimizable variable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Response to Arguments
Applicants’ arguments have been fully considered, but are not found persuasive.
Applicants argue that the Declaration dated 7/14/26 provides evidence of unexpected results [Remarks: p. 6]. The Declaration describes unexpected results found when the human erythropoietin is deposited on the quantum dot in a multivalent fashion20, 50 and 100 nM EPO-QD which correlated to 2, 5 and 10 copies/QD per the description in the specification [0013]. It resulted in a 1.8-fold increase in activity (aquaporin expression).
This is not found persuasive. In response to Applicants’ argument of unexpected results, the Examiner responds with the following statements:
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range (see MPEP § 716.02(d)). In the description of Fig. 4B (i.e., the figure referred to in the Declaration dated 7/14/26), Applicants merely indicate that the data is based on free EPO and a QD bound to EPO at 20, 50, or 100 nM (corresponding to 2, 5 or 10 copies/QD). Applicants do not describe what materials make up the quantum dot (see for example, limitations in instant dependent claims 9-10). Based on the data presented, one does not know if any materials/ingredients would produce the same/similar results. The instant independent claim 8 is broad and includes any known materials to make up the quantum dot. Furthermore, Fig. 4B shows data for 2, 5 and 10 copies/QD, but the instant independent claim 8 has a range that also includes up to 40 molecules of the human erythropoietin per quantum dot. It is noted that the data presented in Fig. 4B does not show a linear relationship with effect and EPO amount and therefore, one of ordinary skill in the art could not predict the effect of, for example, 40 molecules of EPO on a QD.
Conclusion
THIS ACTION IS MADE FINAL. 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 GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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/GENEVIEVE S ALLEY/ Primary Examiner, Art Unit 1617
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