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 Application
Claims 1-12 and 15 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Drawings
The drawings are objected to because Figure 5 axes are blurry and difficult to read. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
Claim 1 recites the terms “plurality” and “nanostructures” which both mean two or more. For the purposes of examination, the examiner interprets the plurality of globular nanostructures as globular nanostructures and any prior art reading on more than one globular nanostructure reads on this claim.
Claim 1 recites “anchoring layer” in line 16. The examiner notes that the specification shows the anchoring layer is a layer that is around the central layer and may or may not have an additional layer attached to it (specification, Figure 2) and that the anchoring layer is capable of reacting with a coating layer (pg 22, lines 24-27). Therefore, for the purposes of examination, the examiner interprets any prior art with an anchoring layer which covers the central part and could be used to anchor a coating layer, reads on this limitation.
Claim Rejections - 35 USC § 112(b)
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, 3, 8-9, and 12 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 recites the limitation "the group" in line 8 and line 10 and line 20 and line 22. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether the groups are the same group or different groups in each case. The examiner recommends amending to “a group” in each case.
Claim 3 recites the limitation "the group" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear which group the “the” refers to whether in claim 3 or a group in claim 1. The examiner recommends amending the “the” to “a”.
Claim 8 recites the limitation "the steps" in line 2. There is insufficient antecedent basis for this limitation in the claim. The use of the word, “the” implies antecedent basis to something earlier. None of the earlier claims have steps in them. It is unclear to what “the steps” refers. The examiner recommends amending removing “the” from “the steps”.
Claim 8 recites the limitation "the group" on pg 4, lines 8 and 10 and on pg 5, lines 5 and 12. There is insufficient antecedent basis for this limitation in the claim. It is unclear which group the “the” refers, whether in claim 8 or a group in claim 3 or claim 1. The examiner recommends amending the “the” to “a”.
Claim 9 recites the limitation "the group" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear which group the “the” refers, whether a group in claim 9 or claim 8 or claim 3 or claim 1. The examiner recommends amending the “the” to “a”.
Claim 12 recites the limitation "the treatment " in line 1-2. There is insufficient antecedent basis for this limitation in the claim. The word “the” implies an earlier treatment, but it is unclear from the earlier claims or from claim 12 to what “the treatment” refers. The examiner recommends amending the “the” to “a”.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 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.
Claim(s) 1-12 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Axelsson, O; et al. US 2017/0106105 A1 (as cited in the IDS filed on 09/06/2024) and Yokozawa, T.; et al. Chain-Growth Polycondensation: Living Polymerization Nature in Polycondensation and Approach to Condensation Polymer Architecture., Polymer Journal, 2004, 36, 2, 65-83 and Rantala, J. US 7,833,820 B2.
Axelsson, O.; et al. (hereafter referred to as Axelsson) is drawn to globular nanostructures comprising a central and peripheral part where the central part is a crosslinked polymeric framework containing chelating groups, and where the peripheral part comprises a polymer attached to the central part (title; abstract). Axelsson teaches that systemic radiotherapy offers many solutions to surgical shortcomings and external radiotherapy and that beta emitters and alpha emitters are both used in systemic radiotherapy (pg 1, para [0003]-[0005]) and that advances in nanotechnology have led to development of novel nanocarriers designed for cancer detection and screening, in vivo molecular and cellular imaging, and delivery of therapeutics (pg 1, para [0006], lines 1-6). Axelsson teaches that globular, bioinert, chelating, polymeric nanostructures may have applications in radiotherapy (pg 1, para [0008], lines 1-3) and that globular nanostructures may have some advantage as a theranostic for diagnosing cancer, delivering tumor-targeted therapy, and monitoring therapy response (pg 2, para [0019], lines 1-15). Axelsson teaches globular nanostructures with a hydrodynamic diameter of 8-100 nm with a central part of 6-90 nm and a peripheral part of the difference between the total and central diameters (pg 2, para [0020], lines 1-6). Axelsson teaches the central part is a crosslinked polymeric framework (pg 2, para [0022], lines 1-4) and contains a chelating part which can be an ester, a phosphonate, or a sulfonate (pg 2, para [0024], lines 3-5) and where the peripheral portion comprises a synthetic polymer attached to the central crosslinked polymer (pg 2, para [0025], lines 1-4). Axelsson teaches the peripheral polymer covers the central part to protect it from interactions with the biological systems (pg 7, par a[0097], lines 1-3) and may be a linear polymer containing PEG (pg 7, para [0098), lines 1-2) and branched polymers (pg 7, para [0100], lines 1-6), and crosslinked polymers (pg 7, para [0101], lines 1-6). Axelsson teaches polymeric framework with a network structure can be achieved with multifunctional monomers such as bis(trimethoxysilyl)methane or bis(trimethoxysilyl)ethane (pg 7, para [0110], lines 1-8 and 17-18) and that trialkoxyorganosilanes are particularly advantageous (pg 8, para [0118], lines 1-10) and that the choice of alkoxy group can be used to control molecular size during production (pg 8, para [0132], lines 1-9). Axelsson teaches the peripheral polymers comprise a multitude of PEG residues covalently attached to the outer parts of the central polymer framework (pg 9, para [0145], lines 1-3) and may be selected from polymeric materials that are hydrophilic, bioinert, and electrically neutral or zwitterionic and may be linear, branched, or crosslinked (pg 11, para [0172], lines 1-9) and can have the structure of a copolymer with PEG as the outer block and can be directly linked to the central polymer framework or there can be a linking polymer (pg 11, para [0173], lines 1-6) where the linking polymer can be a carboxysilyl polymers (pg 11, para [0174]). Axelsson teaches methods of preparing (pg 17, para [0330], lines 1-10), radiolabeling (pg 19, para [0354], lines 1-14), and characterization (pg 21, para [0380], lines 1-12).
As to claim 1, Axelsson teaches a plurality of globular nanostructures (pg 3, para [0029], lines 1-5; pg 3, para [0033], lines 1-3) wherein each nanostructure comprises a central part (abstract; pg 2, para [0020], lines 1-6) where the central part comprises a polymer framework of monomer residues according to Formula (II) (pg 8, par [0130]) wherein R1 and R2 are independently selected from the group consisting of negative charge and H (pg 8, para [0126]) and where prior art recitation of R3, R4, R5, R6, R7, and R8 are equivalent in position to the instant claim 1 “R3” and where they are independently selected from the group consisting of a negative charge, H, and a bond to the polymeric framework (pg 8, para [0130], lines 1-7). This teaches a range of bonding to the polymeric framework from 0-6. The claimed range of “at least 3” overlaps or lies inside the prior art range of 0-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And, Axelsson teaches m is 1-5 (pg 8, para [0130], lines 3 and 7) and wherein the central part has an average hydrodynamic diameter of 6-90 nm (pg 24, para [0401], lines 3-4). The claimed range of 10-90nm lies inside the prior art range of 6-90 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP 2144.05(I).
Axelsson teaches an anchoring layer (pg 24, para [0401], lines 1-3) of a formula A where A is defined as -OSi(OR11)2-(CH2)o-, where prior art recitation of R11, which is equivalent to the instant claimed “R”, are covalent bonds to the central part (pg 26, para [0457], lines 1-3) and where the prior art “o”, which is equivalent to “n”, is 2-5 (pg 26, para [0457], line 3). Axelsson teaches “-“ represents a covalent bond (pg 26, para [0457], line 1-2). And wherein the anchoring layer has an estimated thickness (pg 24, para [0401], lines 1-6) and a thickness of 1-2.5 nm (pg 25, para [0413], lines 1-4). Since the prior art range is an estimated range, the prior art range is about 1-2.5 nm, therefore, it overlaps with the claimed range of 1-5 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Axelsson does not teach dispersity.
Axelsson does not explicity teach formula (I).
Yokozawa, T.; et al. (hereafter referred to as Yokozawa) is drawn to chain-growth polycondensation polymerizations with a variety of polymers (title; abstract). Yokozawa teaches polymerization can be classified into two categories, chain polymerization and step polymerization (pg 65, col 1, para 1, lines 1-2) and that chain polymerization typically results in narrow molecular weight distributions and low dispersity over the whole conversion range (pg 65, col 1, para 1, lines 5-12) and step growth polymerization is difficult to control the molecular weight of the polymer and typically possesses a broad molecular weight distribution and that the dispersity increases up to 2.0 in the final stage of polymerization (pg 65, col 1, para 2, lines 1-11; pg 65, col 2, para 1, line 1). Yokozawa teaches low polydispersities are around 1.2-1.3 (pg 67, col 1, para 2, lines 13-18). Yokozawa teaches homopolymers with dispersities around 1.1 (pg 68, Figure 1) and diblock copolymers with dispersities from 1.1-1.3 (pg 69, Table 1). Yokozawa teaches step growth polymerization with typical dispersities between 1.4-2.1 (pg 80, Table 2; pg 80, col 2, para 1, lines 10-22).
Regarding dispersity, Yokozawa teaches dispersity of 1.4-2.1 (pg 80, Table 2; pg 80, col 2, para 1, lines 10-22).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Axelsson to include dispersity as taught by Yokozawa because there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to a person of ordinary skill in the art, to modify the reference or to combine reference teachings and the modification would have yielded the predictable outcome of a dispersity for the step-growth polymerization crosslinked globular nanostructure as taught by Axelsson.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a dispersity with the globular nanostructure because the prior art of Axelsson disclosed crosslinked polymer system known to have dispersities (pg 6, para [0089], line 5). Additional prior art of Yokozawa suggested dispersity ranges for condensation polymerization to have similar dispersities because of the overlap that both Axelsson and Yokozawa teach condensation polymerization systems.
The skilled artisan would have been motivated to have a dispersity value because it is a routine characterization as taught by Axelsson (pg 6, para [0089], line 1-8). Therefore, it would have been prima facie obvious to combine the teachings of Axelsson with Yokozawa.
The combined teachings of Axelsson and Yokozawa do not explicitly teach the monomer residue according to formula (I).
Rantala, J. (hereafter referred to as Rantala) is drawn to a method of producing disilane monomer which can be polymerized and combined with nanoparticles to provide polymer compositions (title; abstract). Rantala teaches functionalized disilane precursors are applicable for use as dielectrices (col 1, lines 11-15). Rantala teaches organic polymers can be divided into two different groups with respect to behavior of their dielectric constant, nonpolar and polar polymers (col 1, lines 53-67). Rantala teaches siloxane polymers (col 2, lines 55-59), organo-functionalized molecules (col 2, lines 63-65), poly(organo siloxane)s (col 2, lines 64-67), thin films (col 3, lines 1-4), and dielectric layers (col 3, lines 5-6). Rantala teaches a monomer (R1)xSi-R3-Si(R2)y, where R1 is hydrolyzable, R2 is a functional group, R3 is a bridging hydrocarbyl group, and x and y are 1-3 (col 3, lines 30-37) and that the monomer can be homopolymerized or copolymerized with nanoparticles (col 3, lines 38-41) where the polymer is made by condensation polymerization (col 3, lines 60-65) and can undergo crosslinking (col 4, lines 27-31) which enables high chemical resistance (col 4, lines 32-34). Rantala teaches that the crosslinking group of the monomer (col 5, lines 32-39) can be an organic containing silicon group or a reactive cleaving group, or another group (col 5, lines 42-46) and the group between the Si can be alkyl (col 5, lines 53-57) and the hydrolyzable group can be alkoxy or another group (col 6, lines 55-59). Rantala teaches a method of producing the polymer composition (col 8, lines 37-46). Rantala teaches the polymer can be attached to a nanoparticle (col 9, lines 18-24).
Regarding the monomer residue according to formula (I), Rantala teaches the monomer residue according to formula (I) (col 3, lines 38-41; col 5, lines 31-57) where R is selected from the group consisting of covalent bonds (col 5, lines 41-48) where the R groups can be hydrolysable groups which includes alkoxy groups, which can be hydrolyzed to crosslinking (col 5, lines 23-28). The prior art range of R groups which can consist of covalent bonds to a monomer residue of the anchoring layer is 1-6 (col 5, lines 42-46). The claimed range of at least 2 overlaps with the prior art range of 1-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And Rantala teaches n is 1-12 (col 6, lines 7). The claimed range of 1-2 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Axelsson to include monomer according to Formula (I) as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the a modified anchoring layer of Axelsson with the monomer residue of Rantala.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the anchoring layer of Axelsson with the monomer of Rantala because the prior art of Axelsson disclosed the anchoring layer is a polymer with silyl groups (Axelsson, pg 26, para [0455], lines 1-7; pg 26, para [0457], lines 1-3) known to attach to the nanostructure (Axelsson, pg 26, para [0457], lines 2-3) and known to protect the nanostructure from interactions with the biological systems and to be bioinert so that the nanostructure is not degraded (Axelsson, pg 7, para [0097], lines 1-5; pg 11, para [0171], lines 1-6). Additional prior art of Rantala suggested a disilane monomer polymerized and crosslinked covering a nanostructure to have similar property of protecting the nanostructure from degradation (col 4, lines 32-34) because of the overlap of silyl groups covalently bound to the nanostructure with a density to prevent degradation of the nanostructure.
The skilled artisan would have been motivated to modify the silyl groups covering the nanostructure of Axelsson with the disilyl groups taught by Rantala because the silyl groups taught by Rantala can be crosslinked with each other and can form therefore form a stronger protection against degradation of the nanostructure. Therefore, it would have been prima facie obvious to combine the teachings of Axelsson with Rantala.
As to claim 2, Axelsson teaches the anchoring layer has a thickness of 1-2.5 nm. The claimed range of 1.1-2.5 lies inside the prior art range of 1-2.5 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 3, Axelsson teaches 2 R are selected from the group comprising a covalent bond to a monomer residue of the central part (pg 26, para [0457], lines 1-3).
As to claim 4, Rantala teaches n is 1-12 (col 6, lines 7). The claimed value of 1 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Additionally, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. See MPEP 2144.09(I). And, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See 2144.09(II).
As to claim 5, Axelsson teaches m is 1-5 (pg 8, para [0129]). The claimed value of 3 lies inside the prior art range of 1-5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. See MPEP 2144.09(I). And, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See 2144.09(II).
As to claim 6, Axelsson teaches a plurality of globular nanostructures wherein the structures comprise a coating (pg 26, para [0455], lines 1-7).
As to claim 7, Axelsson teaches the coating comprises polyethylene glycol (pg 26, para [0455], lines 3-4).
As to claim 8, Axelsson teaches a method for producing a plurality of globular nanostructures (pg 11, para [0191], lines 1-15) comprising the steps of providing a mixture or precursor nanostructures (pg 11, para [0191], lines 12-13) where the size has an average hydrodynamic diameter of 6-90 nm (pg 24, para [0401], lines 3-4). The claimed range of 10-90nm lies inside the prior art range of 6-90 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP 2144.05(I). And Axelsson teaches where the central polymer framework is a bisphosphonate monomer according to Formula (II) ((pg 8, par [0130]) wherein R1 and R2 are independently selected from the group consisting of negative charge and H (pg 8, para [0126]) and where prior art recitation of R3, R4, R5, R6, R7, and R8 are equivalent in position to the instant claim 1 “R3” and where they are independently selected from the group consisting of a negative charge, H, and a bond to the polymeric framework (pg 8, para [0130], lines 1-7). This teaches a range of bonding to the polymeric framework from 0-6. The claimed range of “at least 3” lies overlaps or lies inside the prior art range of 0-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And, Axelsson teaches m is 1-5 (pg 8, para [0130], lines 3 and 7). Axelsson teaches a monosilyl monomer (pg 24, para [0401], liens 1-3) wherein “-“ is a covalent bond (pg 26, para [0457], line 1-2).
Axelsson teaches placing the plurality of nanostructures and the monomer in a mixture of water and water miscible organic solvent (pg 12, para [0193], lines 1-7).
Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature lies inside the claimed temperature range of 20-150oC. 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. See MPEP 2144.05(II)(A). And Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 1-24 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Axelsson does not explicitly teach formula (III).
Axelsson does not teach the ratio of monomers to nanostructure.
Regarding the monomer residue according to formula (III), Rantala teaches the monomer residue according to formula (III) (col 3, lines 38-41; col 5, lines 31-57) where R is selected from the group consisting of covalent bonds (col 5, lines 41-48) where the R groups can be hydrolysable groups which includes alkoxy groups (col 3, lines 30-34; col 5, lines 23-28) and wherein n is 1-12 (col 6, lines 7). The claimed range of n is 1-2 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Axelsson to include monomer according to Formula (I) as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the a modified anchoring layer of Axelsson with the monomer residue of Rantala.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the monomer of Axelsson with the monomer of Rantala because the prior art of Axelsson disclosed the anchoring layer is a polymer with silyl groups (Axelsson, pg 26, para [0455], lines 1-7; pg 26, para [0457], lines 1-3) known to attach to the nanostructure (Axelsson, pg 26, para [0457], lines 2-3) and known to protect the nanostructure from interactions with the biological systems and to be bioinert so that the nanostructure is not degraded (Axelsson, pg 7, para [0097], lines 1-5; pg 11, para [0171], lines 1-6). Additional prior art of Rantala suggested a disilane monomer polymerized and crosslinked covering a nanostructure to have similar property of protecting the nanostructure from degradation (col 4, lines 32-34) because of the overlap of silyl groups covalently bound to the nanostructure with a density to prevent degradation of the nanostructure.
The skilled artisan would have been motivated to modify the silyl groups covering the nanostructure of Axelsson with the disilyl groups taught by Rantala because the silyl groups taught by Rantala can be crosslinked with each other and can form therefore form a stronger protection against degradation of the nanostructure. Therefore, it would have been prima facie obvious to combine the teachings of Axelsson with Rantala.
Regarding the ratio of monomers to nanostructure, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:20 overlaps with the prior art range of 1: 0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Axelsson to include the ratio of a monomer to nanostructure as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a layer of monomer according to Rantala around the polymer framework of Axelsson.
A person of ordinary skill in the art would have had a reasonable expectation of success in using the ratio of monomer to nanostructure because the prior art of Axelsson disclosed nanoparticles known to have an average diameter of 6-90 nm (Axelsson, pg 2, para [0020], lines 1-6) that are covered with enough silyl monomers to protect against degradation (Axelsson, pg 7, para [0097], lines 1-5; pg 11, para [0171], lines 1-6). Additional prior art of Rantala suggested covering nanostructures of a size of 0.5-20 nm (Rantala, col 11, lines 40-45) to have similar capability of being covered by silyl monomers to protect against degradation (Rantala, col 4, lines 32-34) because of the overlap of covalently binding silyl monomer outer layer to a central nanostructure.
The skilled artisan would have been motivated to use the ratio of Rantala with monomer of Rantala and polymer framework of Axelsson because this ratio has been shown to protect the central part from degradation.
As to claim 9, Rantala teaches a monomer according to Formula (III) of claim 8 where R1, R2, R3, R4, R5, and R6 of the instant claim is equivalent to R1 and R2 -of Rantala (col 5, lines 32-48) and where R1 is alkoxy (col 5, line 49) and R2 is alkoxy (col 3, lines 30-34; col 6, line 55-59) and where the alkyl of the alkoxy is methyl or ethyl (col 6, lines 55-56) and where n is 1-12 (col 5, lines 47-48; col 5, lines 53-54; col 6, lines 6-7). The claimed range of 1 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 10, Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature overlaps the claimed temperature range of 80-150oC. 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. See MPEP 2144.05(II)(A). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And, Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 2-6 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Axelsson does not teach the ratio of monomer to precursor nanostructures.
Regarding the ratio of monomer to precursor nanostructures, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:7 overlaps with the prior art range of 1:0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Axelsson to include the ratio of a monomer to nanostructure as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a layer of monomer according to Rantala around the polymer framework of Axelsson.
A person of ordinary skill in the art would have had a reasonable expectation of success in using the ratio of monomer to nanostructure because the prior art of Axelsson disclosed nanoparticles known to have an average diameter of 6-90 nm (Axelsson, pg 2, para [0020], lines 1-6) that are covered with enough silyl monomers to protect against degradation (Axelsson, pg 7, para [0097], lines 1-5; pg 11, para [0171], lines 1-6). Additional prior art of Rantala suggested covering nanostructures of a size of 0.5-20 nm (Rantala, col 11, lines 40-45) to have similar capability of being covered by silyl monomers to protect against degradation (Rantala, col 4, lines 32-34) because of the overlap of covalently binding silyl monomer outer layer to a central nanostructure.
The skilled artisan would have been motivated to use the ratio of Rantala with monomer of Rantala and polymer framework of Axelsson because this ratio has been shown to protect the central part from degradation.
As to claim 11, Axelsson teaches a pharmaceutical composition comprising a plurality of globular nanostructures (pg 3, para [0029], lines 1-9; pg 27, para [0496], lines 1-5; pg 28, para [0516], lines 1-4).
As to claim 12, Axelsson teaches a pharmaceutical composition for use in the treatment of cancer wherein the pharmaceutical composition comprises a radionuclide (pg 3, para [0027], lines 1-6; pg 3, para [0029], lines 1-9; pg 28, lines 1-4).
As to claim 15, Axelsson teaches a pharmaceutical composition as a carrier of a radioactive isotope (pg 3, para [0027], lines 1-6; pg 3, para [0029], lines 1-9; pg 13, para [0226], lines 1-2; pg 28, lines 1-4).
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 6-8, and 11-14 of U.S. Patent No. 9,040,637 in view of Axelsson, O; et al. US 2017/0106105 A1 (as cited in the IDS filed on 09/06/2024) and Yokozawa, T.; et al. Chain-Growth Polycondensation: Living Polymerization Nature in Polycondensation and Approach to Condensation Polymer Architecture., Polymer Journal, 2004, 36, 2, 65-83 and Rantala, J. US 7,833,820 B2. The teachings of Axelsson, Yokozawa, and Rantala as applied in the rejection above are incorporated in this rejection.
Instant claims are drawn to a plurality of globular nanostructures comprising a central part comprising a polymer from monomers of Formula (II), wherein R1 and R2 are independently negatively charge and H, R3 is independently selected from negative charge, H, a covalent bond to the polymeric framework, and wherein at least 3 R3 are bonds to polymeric framework an m is 1-5 and it has a size of 10-90 nm; and an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bond to a monomer residue of the central part and a covalent bond to a Formula (I) residue wherein n is 1-2 and the thickness is 1-5 nm; and the nanostructures further comprise hydrophilic groups, comprising polyethylene glycol; and a method of producing these globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20 and a temperature of 20-150oC for 1-24 hr; and a pharmaceutical composition of the globular nanostructures comprising a radioactive isotope.
The conflicting claims of U.S. Patent No. 9,040,637 (hereafter referred to as '637) are drawn to a polymeric nanostructure comprising monomers of Formula (II), wherein R1 and R2 are independently selected from the group consisting of a negative charge and H and at least R3 (noted as R3 and R4 in the conflicting claims of '637) can be attached to the polymer framework and is the rest of Formula (II) and has a size 3-20 nm; and the conflicting claims of '637 teach an hydrophilic outer part comprising polyethylene glycol; and a pharmaceutical composition.
The conflicting claims of '637 do not teach an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bonds to a monomer residue or the central part and a covalent bond to a Formula (I) residue wherein N is 1-2 and the thickness is 1-5 nm.
The conflicting claims of '637 do not teach the molar ratio of monomer to nanostructure of 1:0.5 to 1:20.
The conflicting claims of '637 do not teach the temperature of 20-150oC for 1-24 hr.
The conflicting claims of '637 do not teach a pharmaceutical composition of globular nanostructures comprising a radioactive isotope.
Regarding Formula (I), Rantala teaches the monomer residue according to formula (I) (col 3, lines 38-41; col 5, lines 31-57) where R is selected from the group consisting of covalent bonds (col 5, lines 41-48) where the R groups can be hydrolysable groups which includes alkoxy groups, which can be hydrolyzed to crosslinking (col 5, lines 23-28). The prior art range of R groups which can consist of covalent bonds to a monomer residue of the anchoring layer is 1-6 (col 5, lines 42-46). The claimed range of at least 2 overlaps with the prior art range of 1-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And Rantala teaches n is 1-12 (col 6, lines 7). The claimed range of 1-2 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of conflicting claims ’637 to include a monomer according to Formula (I) as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the a modified polymeric framework of conflicting claims ‘637 with the monomer residue of Rantala.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the framework of conflicting claims ‘637 with the monomer of Rantala because the prior art of conflicting claims of ‘637 disclosed a polymeric framework with a coating layer known to attach to the nanostructure and known to protect the nanostructure from interactions with the biological systems and to be bioinert so that the nanostructure is not degraded. Additional prior art of Rantala suggested a disilane monomer polymerized and crosslinked covering a nanostructure to have similar property of protecting the nanostructure from degradation (Rantala, col 4, lines 32-34) because of the overlap of silyl groups covalently bound to the nanostructure with a density to prevent degradation of the nanostructure.
The skilled artisan would have been motivated to modify the silyl groups covering the nanostructure of conflicting claims o ’637 with the disilyl groups taught by Rantala because the silyl groups taught by Rantala can be crosslinked with each other and can form therefore form a stronger protection against degradation of the nanostructure. Therefore, it would have been prima facie obvious to combine the teachings of conflicting claims of ‘637 with Rantala.
Regarding the molar ratio, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:7 overlaps with the prior art range of 1: 0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the reaction temperature of 20-150oC with a reaction time of 1-24 hr, Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature lies inside the claimed temperature range of 20-150oC. 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. See MPEP 2144.05(II)(A). And, Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 2-6 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the conflicting claims and Rantala to include reaction temperature and reaction time as taught by Axelsson because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method with a reaction temperature of 20-150oC and a reaction time of 1-24 hrs.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the method because the prior art of Rantala disclosed polymerization temperatures known to be in a similar range of 20-200oC. Additional prior art of Axelsson suggested polymerization under similar temperatures and suggested a reaction time for the temperatures to have similar result of producing a polymer because of the overlap of the type of polymerization performed.
The skilled artisan would have been motivated to use this reaction temperature for this length of time because the Axelsson demonstrates that the polymerization similar to Rantala can be done in this time frame.
Regarding a pharmaceutical composition of globular nanostructures comprising a radioactive isotope, Axelsson teaches a pharmaceutical composition as a carrier of a radioactive isotope (pg 3, para [0027], lines 1-6; pg 3, para [0029], lines 1-9; pg 13, para [0226], lines 1-2; pg 28, lines 1-4).
Claims 1-12 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-8 of U.S. Patent No. 9,999,693 in view of Axelsson, O; et al. US 2017/0106105 A1 (as cited in the IDS filed on 09/06/2024) and Yokozawa, T.; et al. Chain-Growth Polycondensation: Living Polymerization Nature in Polycondensation and Approach to Condensation Polymer Architecture., Polymer Journal, 2004, 36, 2, 65-83 and Rantala, J. US 7,833,820 B2. The teachings of Axelsson, Yokozawa, and Rantala as applied in the rejection above are incorporated in this rejection.
Instant claims are drawn to a plurality of globular nanostructures comprising a central part comprising a polymer from monomers of Formula (II), wherein R1 and R2 are independently negatively charge and H, R3 is independently selected from negative charge, H, a covalent bond to the polymeric framework, and wherein at least 3 R3 are bonds to polymeric framework an m is 1-5 and it has a size of 10-90 nm; and an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bond to a monomer residue of the central part and a covalent bond to a Formula (I) residue wherein n is 1-2 and the thickness is 1-5 nm; and the nanostructures further comprise hydrophilic groups, comprising polyethylene glycol; and a method of producing these globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20 and a temperature of 20-150oC for 1-24 hr; and a pharmaceutical composition of the globular nanostructures comprising a radioactive isotope.
The conflicting claims of U.S. Patent No. 9,999,693 (hereafter referred to as '693) are drawn to globular nanostructure comprising monomers according to Formula (II) wherein R1 and R2 are independently selected from negative charge, H, and some are bound to the polymer framework and where the equivalent of m is 2-5; and the central part has a size of 8-100 nm; and an outer layer which comprises a hydrophilic polymer which comprises polyethylene glycol; and wherein the nanostructure comprises radionuclides.
The conflicting claims of '693 do not teach an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bonds to a monomer residue or the central part and a covalent bond to a Formula (I) residue wherein n is 1-2 and the thickness is 1-5 nm.
The conflicting claims of '693 do not explicitly teach the size of the outer layer.
The conflicting claims of '693 do not teach a method of producing the globular nanostructures.
The conflicting claims of '693 do not teach the molar ratio of monomer to nanostructure of 1:0.5 to 1:20.
The conflicting claims of '693 do not teach the temperature of 20-150oC for 1-24 hr.
The conflicting claims of '693 do not teach a pharmaceutical composition of globular nanostructures.
Regarding Formula (I), Rantala teaches the monomer residue according to formula (I) (col 3, lines 38-41; col 5, lines 31-57) where R is selected from the group consisting of covalent bonds (col 5, lines 41-48) where the R groups can be hydrolysable groups which includes alkoxy groups, which can be hydrolyzed to crosslinking (col 5, lines 23-28). The prior art range of R groups which can consist of covalent bonds to a monomer residue of the anchoring layer is 1-6 (col 5, lines 42-46). The claimed range of at least 2 overlaps with the prior art range of 1-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And Rantala teaches n is 1-12 (col 6, lines 7). The claimed range of 1-2 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of conflicting claims ’693 to include a monomer according to Formula (I) as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the a modified polymeric framework of conflicting claims ‘693 with the monomer residue of Rantala.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the framework of conflicting claims ‘693 with the monomer of Rantala because the prior art of conflicting claims of ‘693 disclosed a polymeric framework with a coating layer known to attach to the nanostructure and known to protect the nanostructure from interactions with the biological systems and to be bioinert so that the nanostructure is not degraded. Additional prior art of Rantala suggested a disilane monomer polymerized and crosslinked covering a nanostructure to have similar property of protecting the nanostructure from degradation (Rantala, col 4, lines 32-34) because of the overlap of silyl groups covalently bound to the nanostructure with a density to prevent degradation of the nanostructure.
The skilled artisan would have been motivated to modify the silyl groups covering the nanostructure of conflicting claims o ’693 with the disilyl groups taught by Rantala because the silyl groups taught by Rantala can be crosslinked with each other and can form therefore form a stronger protection against degradation of the nanostructure. Therefore, it would have been prima facie obvious to combine the teachings of conflicting claims of ‘693 with Rantala.
Regarding the molar ratio, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:7 overlaps with the prior art range of 1: 0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the reaction temperature of 20-150oC with a reaction time of 1-24 hr, Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature lies inside the claimed temperature range of 20-150oC. 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. See MPEP 2144.05(II)(A). And, Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 2-6 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the conflicting claims and Rantala to include reaction temperature and reaction time as taught by Axelsson because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method with a reaction temperature of 20-150oC and a reaction time of 1-24 hrs.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the method because the prior art of Rantala disclosed polymerization temperatures known to be in a similar range of 20-200oC. Additional prior art of Axelsson suggested polymerization under similar temperatures and suggested a reaction time for the temperatures to have similar result of producing a polymer because of the overlap of the type of polymerization performed.
The skilled artisan would have been motivated to use this reaction temperature for this length of time because the Axelsson demonstrates that the polymerization similar to Rantala can be done in this time frame.
Regarding a method of producing the globular nanostructures, Axelsson teaches a method for producing a plurality of globular nanostructures (pg 11, para [0191], lines 1-15) comprising the steps of providing a mixture or precursor nanostructures (pg 11, para [0191], lines 12-13) where the size has an average hydrodynamic diameter of 6-90 nm (pg 24, para [0401], lines 3-4). The claimed range of 10-90nm lies inside the prior art range of 6-90 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP 2144.05(I). And, Axelsson teaches placing the plurality of nanostructures and the monomer in a mixture of water and water miscible organic solvent (pg 12, para [0193], lines 1-7).
Regarding the size of the outer layer, Axelsson teaches the anchoring layer has a thickness of 1-2.5 nm. The claimed range of 1.1-2.5 lies inside the prior art range of 1-2.5 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding a pharmaceutical composition of globular nanostructures, Axelsson teaches a pharmaceutical composition comprising a plurality of globular nanostructures (pg 3, para [0029], lines 1-9; pg 27, para [0496], lines 1-5; pg 28, para [0516], lines 1-4).
Claims 1-12 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 12-14, and 17 of copending Application No. 18/841,621 in view of Axelsson, O; et al. US 2017/0106105 A1 (as cited in the IDS filed on 09/06/2024) and Yokozawa, T.; et al. Chain-Growth Polycondensation: Living Polymerization Nature in Polycondensation and Approach to Condensation Polymer Architecture., Polymer Journal, 2004, 36, 2, 65-83 and Rantala, J. US 7,833,820 B2. The teachings of Axelsson, Yokozawa, and Rantala as applied in the rejection above are incorporated in this rejection.
Instant claims are drawn to a plurality of globular nanostructures comprising a central part comprising a polymer from monomers of Formula (II), wherein R1 and R2 are independently negatively charge and H, R3 is independently selected from negative charge, H, a covalent bond to the polymeric framework, and wherein at least 3 R3 are bonds to polymeric framework an m is 1-5 and it has a size of 10-90 nm; and an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bond to a monomer residue of the central part and a covalent bond to a Formula (I) residue wherein n is 1-2 and the thickness is 1-5 nm; and the nanostructures further comprise hydrophilic groups, comprising polyethylene glycol; and a method of producing these globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20 and a temperature of 20-150oC for 1-24 hr; and a pharmaceutical composition of the globular nanostructures comprising a radioactive isotope.
The conflicting claims of U.S. Application No. 18/841,621 (hereafter referred to as '621) is drawn to a plurality of globular nanostructures with a dispersity between 1 and 1.8 comprising monomers of Formula (II), wherein R1 and R2 are independently negatively charged and H and wherein at least 3 R3 are bonds to the polymeric framework; and n is 1-5; and has a size of 13-90 nm; an temperature of 110-160oC; and a pharmaceutical composition comprising a radioactive isotope.
The conflicting claims of '621 do not teach an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bonds to a monomer residue or the central part and a covalent bond to a Formula (I) residue wherein N is 1-2 and the thickness is 1-5 nm.
The conflicting claims of '621 do not teach a hydrophilic outer layer comprising polyethylene glycol
The conflicting claims of '621 do not teach the molar ratio of monomer to nanostructure of 1:0.5 to 1:20.
The conflicting claims of '621 do not explicitly teach a time of 1-24 hrs.
Regarding Formula (I), Rantala teaches the monomer residue according to formula (I) (col 3, lines 38-41; col 5, lines 31-57) where R is selected from the group consisting of covalent bonds (col 5, lines 41-48) where the R groups can be hydrolysable groups which includes alkoxy groups, which can be hydrolyzed to crosslinking (col 5, lines 23-28). The prior art range of R groups which can consist of covalent bonds to a monomer residue of the anchoring layer is 1-6 (col 5, lines 42-46). The claimed range of at least 2 overlaps with the prior art range of 1-6. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And Rantala teaches n is 1-12 (col 6, lines 7). The claimed range of 1-2 lies within the prior art range of 1-12. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of conflicting claims ’621 to include a monomer according to Formula (I) as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of the a modified polymeric framework of conflicting claims ‘621 with the monomer residue of Rantala.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the framework of conflicting claims ‘621 with the monomer of Rantala because the prior art of conflicting claims of ‘621 disclosed a polymeric framework with a coating layer known to attach to the nanostructure and known to protect the nanostructure from interactions with the biological systems and to be bioinert so that the nanostructure is not degraded. Additional prior art of Rantala suggested a disilane monomer polymerized and crosslinked covering a nanostructure to have similar property of protecting the nanostructure from degradation (Rantala, col 4, lines 32-34) because of the overlap of silyl groups covalently bound to the nanostructure with a density to prevent degradation of the nanostructure.
The skilled artisan would have been motivated to modify the silyl groups covering the nanostructure of conflicting claims o ’621 with the disilyl groups taught by Rantala because the silyl groups taught by Rantala can be crosslinked with each other and can form therefore form a stronger protection against degradation of the nanostructure. Therefore, it would have been prima facie obvious to combine the teachings of conflicting claims of ‘621 with Rantala.
Regarding the molar ratio of monomer to nanostructure of 1:0.5 to 1:20, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:7 overlaps with the prior art range of 1:0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the reaction time of 1-24 hr, Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature lies inside the claimed temperature range of 20-150oC. 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. See MPEP 2144.05(II)(A). And, Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 2-6 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the conflicting claims and Rantala to include reaction temperature and reaction time as taught by Axelsson because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method with a reaction temperature of 20-150oC and a reaction time of 1-24 hrs.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the method because the prior art of Rantala disclosed polymerization temperatures known to be in a similar range of 20-200oC. Additional prior art of Axelsson suggested polymerization under similar temperatures and suggested a reaction time for the temperatures to have similar result of producing a polymer because of the overlap of the type of polymerization performed.
The skilled artisan would have been motivated to use this reaction temperature for this length of time because the Axelsson demonstrates that the polymerization similar to Rantala can be done in this time frame.
Regarding hydrophilic outer layer comprising polyethylene glycol, Axelsson teaches a plurality of globular nanostructures wherein the structures comprise a coating (pg 26, para [0455], lines 1-7) and that coating comprises a hydrophilic polymer, polyethylene glycol (pg 26, para [0455], lines 3-4).
This is a provisional nonstatutory double patenting rejection.
Claims 1-12 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-10, 14, and 16 of copending Application No. 18/844,721 in view of Axelsson, O; et al. US 2017/0106105 A1 (as cited in the IDS filed on 09/06/2024) and Yokozawa, T.; et al. Chain-Growth Polycondensation: Living Polymerization Nature in Polycondensation and Approach to Condensation Polymer Architecture., Polymer Journal, 2004, 36, 2, 65-83 and Rantala, J. US 7,833,820 B2. The teachings of Axelsson, Yokozawa, and Rantala as applied in the rejection above are incorporated in this rejection.
Instant claims are drawn to a plurality of globular nanostructures comprising a central part comprising a polymer from monomers of Formula (II), wherein R1 and R2 are independently negatively charge and H, R3 is independently selected from negative charge, H, a covalent bond to the polymeric framework, and wherein at least 3 R3 are bonds to polymeric framework an m is 1-5 and it has a size of 10-90 nm; and an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or a covalent bond, wherein at least two R are independently covalent bond to a monomer residue of the central part and a covalent bond to a Formula (I) residue wherein n is 1-2 and the thickness is 1-5 nm; and the nanostructures further comprise hydrophilic groups, comprising polyethylene glycol; and a method of producing these globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20 and a temperature of 20-150oC for 1-24 hr; and a pharmaceutical composition of the globular nanostructures comprising a radioactive isotope.
The conflicting claims of U.S. Application No. 18/844,721 (hereafter referred to as '721) is drawn to plurality of globular nanostructures from Formula (II), wherein R1 and R2 are independently selected from the group consisting of a negative charge and H and a covalent bond; and m is 2-5; and has a size of 22-37 nm; and an outer layer comprising a polymer of Formula (I) monomers wherein R is independently selected from negative charge, H, or covalent bond, and wherein n is 1-2; and a coating layer comprising hydrophilic groups, comprising polyethylene glycol; and a pharmaceutical composition of the globular nanostructures comprising radionuclides.
The conflicting claims of '721 do not explicitly teach 3 R3 are bonds to polymeric framework.
The conflicting claims of '721 do not teach the anchoring layer is covalently bound to the polymeric framework.
The conflicting claims of '721 do not teach the thickness of the anchoring layer is 1-5 nm.
The conflicting claims of '721 do not teach a method of producing these globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20.
The conflicting claims of '721 do not teach a reaction temperature of 20-150oC for 1-24 hrs.
Regarding the bonds to the polymeric framework, , Axelsson teaches where the prior art recitation of R3, R4, R5, R6, R7, and R8 are equivalent in position to the instant claim 1 “R3” and where they are independently selected from the group consisting of a negative charge, H, and a bond to the polymeric framework (pg 8, para [0130], lines 1-7).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the conflicting claims of ‘721 to include explicit teachings of bonding to the polymeric framework as taught by Axelsson because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of bonds to the polymeric framework.
A person of ordinary skill in the art would have had a reasonable expectation of success in making bonds to the polymeric framework because the conflicting claims of ‘721 disclosed a central monomer known to have cross-linkable groups. Additional prior art of Axelsson suggested a central monomer to have similar structure and is known to be bound to the polymeric framework and due to the overlap of the structural similarities between the central part monomers of conflicting claims
‘721 and Axelsson, the monomers are expected to behave according to known chemistry in the art.
The skilled artisan would have been motivated to explicit bond to the polymeric framework because this creates more stable globular nanoparticles.
Regarding the anchoring layer is covalently bound to the polymeric framework, Axelsson teaches an anchoring layer (pg 24, para [0401], lines 1-3) of a formula A where A is defined as -OSi(OR11)2-(CH2)o-, where prior art recitation of R11, which is equivalent to the instant claimed “R”, are covalent bonds to the central part (pg 26, para [0457], lines 1-3).
Regarding the anchoring layer is 1-5 nm, ). And wherein the anchoring layer has an estimated thickness (pg 24, para [0401], lines 1-6) and a thickness of 1-2.5 nm (pg 25, para [0413], lines 1-4). Since the prior art range is an estimated range, the prior art range is about 1-2.5 nm and therefore, overlaps with the claimed range of 1-5 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the method of producing globular nanostructures at a mole ratio of monomer to nanostructure of 1:0.5 to 1:20, Rantala teaches a ratio of monomer according to formula (III) to nanostructure as 100:1 to 100:500 (col 29, lines 23-30). This is equivalent to 1:0.01 to 1:5. The claimed range of 1:0.5 to 1:7 overlaps with the prior art range of 1:0.01 to 1:5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the conflicting claims and Axelsson to include the ratio of a monomer to nanostructure as taught by Rantala because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a layer of monomer according to Rantala around the polymer framework of Axelsson.
A person of ordinary skill in the art would have had a reasonable expectation of success in using the ratio of monomer to nanostructure because the prior art of Axelsson disclosed nanoparticles known to have an average diameter of 6-90 nm (Axelsson, pg 2, para [0020], lines 1-6) that are covered with enough silyl monomers to protect against degradation (Axelsson, pg 7, para [0097], lines 1-5; pg 11, para [0171], lines 1-6). Additional prior art of Rantala suggested covering nanostructures of a size of 0.5-20 nm (Rantala, col 11, lines 40-45) to have similar capability of being covered by silyl monomers to protect against degradation (Rantala, col 4, lines 32-34) because of the overlap of covalently binding silyl monomer outer layer to a central nanostructure.
The skilled artisan would have been motivated to use the ratio of Rantala with monomer of Rantala and polymer framework of Axelsson because this ratio has been shown to protect the central part from degradation.
Regarding a reaction temperature of 20-150oC for a reaction time of 1-24 hrs, Axelsson teaches heating the mixture to a temperature from 40-130oC (pg 12, para [0196], lines 1-4). This temperature lies inside the claimed temperature range of 20-150oC. 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. See MPEP 2144.05(II)(A). And, Axelsson teaches a reaction time of 6-48 hrs (pg 12, para [0197], lines 1-6). The claimed range of 1-24 hrs overlaps with the prior art range of 6-48 hrs. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowed.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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