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 .
Election/Restriction
Restriction Requirement
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1-7, drawn to a method of inducing expression of aquaporin-4 comprising providing a bioconjugate comprising a quantum dot bound to human erythropoietin; and contacting human astrocytes with the bioconjugate, thereby inducing expression of aquaporin-4 by the human astrocytes, classified in CPC A61k 49/0067.
II. Claims 8-14, drawn to a composition comprising a bioconjugate comprising a quantum dot bound to human erythropoietin, classified in CPC A61K 33/242.
III. Claims 15-21, drawn to a method comprising providing a quantum dot; and forming a bioconjugate by depositing erythropoietin onto the surface of the quantum dot, classified in CPC A61K 47/64.
The inventions are independent or distinct, each from the other because:
Inventions III and II are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make another and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP § 806.05(f)). In the instant case, the product as claimed can be made by another and materially different process; for example, utilizing a His-tag on the erythropoietin for binding a quantum dot.
Inventions II and I are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, the process for using the product as claimed can be practiced with another materially different product; for example, hyperosmolar conditions such as mannitol can induce aquaporin-4 expression.
Inventions I and III are unrelated. Inventions are unrelated if it can be shown that they are not disclosed as capable of use together and they have different designs, modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the different inventions have different effects.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries); and
(d) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Election of Species
This application contains claims directed to the following patentably distinct species:
Types of quantum dots: If Group I is elected, pick between claims 2 or 3; if Group II is elected, pick between claims 9 or 10; and if Group III is elected, pick between claims 16 or 17
The species are independent or distinct because the different compounds are structurally and likely functionally distinct and further capable of separate utility. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, claims 1, 8 and 15 are generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter; and
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries).
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
During a telephone conversation with Joseph Grunkemeyer on 2/3/26 a provisional election was made without traverse to prosecute the invention of Group II, claims 8-14; and of quantum dot species from claim 9 (not claim 10). Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-7, 10 and 15-21 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Examiner’s note: upon a full search of the elected invention, the Examiner hereby withdraws the election of species as both the species in claim 9 and 10 were found in the same search.
Claims 8-14 are currently under examination.
Claim Objections
Claim9 is objected to because of the following informalities: the claim recites “…an outer zinc sulfide shell in contact the inner cadmium sulfide shell”. The Examiner suggests amending to read: “…an outer zinc sulfide shell in contact with the inner cadmium sulfide shell”.
Appropriate correction is required.
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 –
(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.
Claim 8 is rejected 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).
Yoo is directed to erythropoietin (EPO)-derived peptide MK-X [Title and Abstract].
With regards to instant claim 8, Yoo teaches EPO-conjugated quantum dots (QDs) [p. 9, 1st ¶ in 1st col. and p. 12, last ¶ in 1st col.].
Therefore, by teaching all the limitations of claim 8, Yoo anticipates the instant invention as claimed.
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.
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 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2013/0045499; published: 2/21/13), in view of Clausen et al. (US 2017/0369905; published: 12/28/17).
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 14.
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 8-14 are rejected under 35 U.S.C. 103 as being unpatentable over Medintz et al. (US 2013/0045499; published: 2/21/13), in view of Clausen et al. (US 2017/0369905; published: 12/28/17) and Fatima et al. (J. Funct. Biomater. 2021, 12, 75; in IDS dated 6/20/25).
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].
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 14.
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.
Conclusion
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