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/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 08/07/2026 is acknowledged.
Claims 16-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II, III and IV, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/07/2026.
Status of Claims
Claims 16-25 are withdrawn for being drawn to nonelected groups.
Claims 1-15 are pending and being examined on the merits herein.
Priority
The instant application 18857424, filed on 10/16/2024 is a 371 of PCT/US2023/018982, filed on 04/18/2023, which claims domestic benefit of 63/332,251, filed on 04/18/2022 and 63/332,565, filed on 04/19/2022.
Information Disclosure Statement
The information disclosure statement (IDS), filed on 01/16/2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
Examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 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 polymer includes recurring units of X1 is CH3” and “the polymer includes recurring units of X1 is H”. It’s unclear as currently written whether the limitations are referring to the polymer having -S-CHX1-CH2- units with a particular X1 is recurring, or the X1 just by itself is as the recurring unit. The written language expresses to mean the X1 is recurring, however, the structure in formula (I) as shown appears to represent that the units -S-CHX1-CH2- with a particular X1 is recurring. The written language fails to express a definite meaning.
Claims 2 and 5-6 each recites “recurring units of X1 is ...”. As discussed above, it is unclear whether the recurring unit is X1 itself or the unit -S-CHX1-CH2- with a particular X1.
Claims 3-4 and 7-15 are rejected accordingly because they directly or indirectly depend on claim 1, and they do not further clarify the issue addressed above in claim 1.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites “microparticle has a diameter of about 5 um to ...”. However, the microparticle diameter in claim 1, which claim 3 depends upon, is defined as “greater than 5 um”, i.e., not including the value of 5 um. Therefore, claim 3 rather broadens the diameter range to include 5 um from “greater than 5 um” in claim 1 microparticle diameter, and fails to further limit the subject matter.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-3, 5-8 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Rehor (Polypropylene sulfide nanoparticles as drug carriers, Dissertation, 2005, IDS of 01/16/2025, complete version uploaded, PTO-892) in view of Malakhov et al. (WO2009015286, 01/29/2009, PTO-892).
Rehor throughout the reference teaches polysulfides synthesized by a novel anionic ring opening polymerization in emulsion, and the polymerization facilitates the production of nanoparticles for drug delivery (e.g., Summary).
For Claims 1 and 2, Rehor teaches polymers resulting from standard emulsion polymerization comprising recurring units of formula (I) (copied below, Fig. 1, Pg. 34). The polymer products (in Fig. 1 as shown in box) comprise recurring unit n, corresponding to instantly claimed X1 is CH3, and recurring unit m containing CH2-CH2-S, corresponding to instantly claimed X1 is H:
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Rehor states that ethylene sulfide (S-CH2-CH2-S, Pg. 36, 2nd paragraph) is polymerized in 1:1 mixture with propylene sulfide (in which X1 is CH3) to achieve a statistical copolymerization (e.g., Pg. 36, 4th paragraph). Therefore, the recurring units of X1 is H or X1 is CH3 can be both at 50 mol% of the polymer, falling within the claimed ranges in instant claims 1 and 2.
Rehor characterizes the propylene and ethylene sulfide copolymerization products having particle size 178 nm or 114 nm (Table 4, Pg. 43).
For Claims 5 and 6, Rehor presents the number average degree of polymerization (corresponding to repeating times) of propylene and ethylene sulfide copolymerization products as 22 (statistical copolymerization) and 62.2 (block copolymerization) (Table 4, Pg. 43), falling within the repeating times of 25 to 2,000, and 5 to 1,000 times in instant claims 5 and 6, respectively.
For Claim 7, REHOR discloses the average degree of polymerization of the poly(ethylene sulfide)-co-poly(propylene sulfide block copolymer is 62 (Pg. 43, Table 4) with ethylene sulfide/ propylene sulfide molar ratio 1 (Pg. 36, 4th paragraph), considering MW of ethylene sulfide=60 and MW of propylene sulfide= 74, the number average molecular weight of the poly(ethylene sulfide)-co-poly(propylene sulfide) block copolymer is expected to be (60+74)*62/2= 4154 Da, corresponding to the polymer average molecular weight of about 1,000 Da to about 200,000 Da as recited in instant claim 7.
For Claim 8, Rehor discloses wherein the polymer is a random copolymer (Pg. 43, table 4, the poly(ethylene sulfide)-co-poly(propylene sulfide) copolymer was produced as a statistical or random copolymer, or block copolymer; Pg. 36, 4th paragraph; Pg. 43, Table 4). Rehor indicates that starting from a 1:1 ethylene sulfide/propylene sulfide ratio in the feed, the random and the blocky copolymers are obtained presenting 1.1:1 or a 1:1 ethylene sulfide/propylene sulfide ratio, respectively based on NMR analysis (Pg. 41, bottom paragraph).
For Claim 11, Rehor teaches loading drugs into the nanoparticles., e.g., iodinated oil, vitamin D (starting from Pg. 78, 1st paragraph), 5% Doxorubicin (Pg. 75, 3rd paragraph; Pg. 79, starting 1st paragraph).
For Claim 12, Rehor teaches the nanoparticle comprises a pharmaceutical drug, e.g., Doxorubicin is known as anticancer drug (Pg. 73, 2nd paragraph).
For Claim 15, Rehor teaches the nanoparticle can load with 5% w/w Doxorubicin (Pg. 75, 3rd paragraph).
Rehor does not teach the particles are microparticles with diameter greater than 5 um as recited in instant claim 1 or about 5 um to about 500 um in instant claim 3. Rehor does not teach crystallinity of the polymer great than or equal to 1% as measured as recited in instant claim 4. Rehor does not teach the biologically active agent comprising species as recited in instant claims 13 and 14, Rehor does not teach active agent amount at about 0.05% to about 2% by weight of the microparticle as recited in instant claim 15.
Malakhov throughout the reference teaches microspheres useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions (e.g., Abstract).
Malakhov teaches that producing protein and other macromolecular microparticles and small molecule microparticles with uniform-sized microparticle for delivery (Pg. 2, Lines 16-19). Malakhov indicates that polymers can include repeating units, e.g., 5, 10, 15, 20, hundreds, thousands, up to millions of repeating units, such as polyethylene, polypropylene, cellulose, agarose, polysaccharides, etc. (e.g., Pg. 20, Line 21- Pg. 21, Line 10) as a counterion (Pg. 36, lines 5 and 17-21). Microparticles can be formed as counterion of their own, or act as carriers of compound of interest (e.g., Pg. 37, Lines 13-17), while the counterion and the compound can be identical or different from one another (Claims 12-13), and the molecular weight of the compound can be 1000 to five billion Daltons (Claims 15-33).
Malakhov specifies that for optimal efficacy, the compound ideally should be prepared in the form of discrete microspheres, which are solid or semi-solid particles having a diameter of between 1.5 and 5.0 microns, and it is desirable for the microparticle to have as high a content of the compound as possible, in a form that maintains its activity for concentrated delivery and therapeutic efficacy (Pg. 1 Line 29 -Pg. 2, Line 2), while the microparticle size range (average length, width or diameter) of about or at 0.001 um to about at 500 microns that contain the compound of interest (e.g., Pg. 23, Lines 25-27), overlapping with diameter greater than 5 um as recited in instant claim 1, or about 5 um to about 500 um in instant claim 3.
Malakhov teaches that macromolecules having therapeutic function, nutraceutical function, cosmetic function, or a biological function such as nucleic acid, peptide, protein, hormone, cytokine, chemokine, can be compounds belonging to classes of compounds selected from among hormones, antibiotics, chemotherapeutic agents, anti-infective agents, anti-inflammatory agents, etc., carried by the microparticles (e.g., Pg. 20, Lines 1-20; ), macromolecules selected from polynucleotide, a nucleic acid selected from DNA, RNA and PNA (e.g., Claims 56-57; Claims 179-180), virus, virus particles, etc. (Claims 35-37) (corresponding to instant claims 12-13), wherein RNA can be selected from siRNA, tRNA, snRNA and ribozymes (e.g., Claim 58 and 181) (corresponding to instant claim 14).
Malakhov specifies that the amount of compound in the microparticles is from about or at 0.1% to about or at 99% or greater, w/w; about or at 0.2% to about or at 95% or greater, w/w; about or at 0.5% to about or at 90% or greater, w/w; about or at 1% to about or at 85% or greater, w/w (Claims 203-206), overlapping with active agent amount about 0.05% to about 2% in instant claim 15.
It would have been prima facie obvious for a person with ordinary skills in the art prior to filing date to incorporate Malakhov’s teaching of microparticle into the drug delivery carrier of Rehor to arrive at current invention. Because Rehor indicates that the nanoparticles unfortunately cannot be used to deliver peptides, proteins or DNA/RNA (Pg. 73, 2nd paragraph), and teaches that a large amount of research is devoted to alternative carrier types such as macromolecular drugs, with microparticles, especially for vaccine delivery and others (Pg. 3, 1st paragraph), while Malakhov demonstrates that microparticles capable of carrying or forming proper sized particles for achieving optimal efficacy of drug delivery, an artisan in the field would have motivated to increase the nanoparticle size in Rehor to make microparticles that would facilitate both macromolecular and small molecular drug delivery as taught by Malakhov. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D). Moreover, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
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 In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). For this instance, the microparticle diameter, the recurring unit molar amount, and active agent amount overlap with those taught by prior art. Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Rehor (Polypropylene sulfide nanoparticles as drug carriers, Dissertation, 2005, IDS of 01/16/2025, complete version uploaded, PTO-892) in view of Malakhov et al. (WO2009015286, 01/29/2009, PTO-892) as applied to claims 1-3, 5-8 and 11-15 above, further in view of Simon Weizmiller (X-ray diffraction analysis of polymers, ThermoFisher Scientific, 03/11/2021, PTO-892).
Combined teaching of Rehor and Malakhov teaches a microparticle comprising the poly ES/PS ( ethylene sulfide/propylene sulfide) with recurring units of formula (I) as in instant claim 1, and recurring units of X1 is CH3 and X1 is H can be in the molar ratio 1:1 in polymerization to achieve the random copolymer; microparticle diameter for optimal drug compound delivery can be greater than 5 um to up to 500 um, as discussed above and applied to claims 1-3, 5-8 and 11-15 in detail, and incorporated herein.
Malakhov further teaches that the quality of the microspheres is scored based on uniformity of the microspheres, the absence of glass-like crystalline forms and absence of aggregates, and the lyophilized powders are analyzed by light microscopy (e.g., Pg. 156, Lines 13-18), indicating that presence of exclusive crystalline particles (glass like crystals) as a score 0 as 100% absent of microspheres, while score 10 as total absent of crystalline particles, and score 5 as microspheres are dominant with scarce crystals; score 2 as scarce microspheres with highly dominant crystals (Table 13, Pg. 157). Malakhov presents that many different combinations used to produce microspheres of different compounds, with resulting microsphere quality scores ranging from 2-9 (e.g., Table 14, compound tobramycin, Pg. 157), 0-9 (e.g., Table 14, compound kanamycin, Pg. 158), 0-7 (siRNA table, Pg. 161-162), etc., implying the crystallinity in the microparticles can range from exclusive (total crystals) to almost absent (almost all microspheres) based on the quality scale in Table 13, which would overlap with the crystallinity greater than or equal to 1% as recited in instant claim 4.
Malakhov does not teach using X-ray diffractive spectroscopy to measure crystallinity.
Simon teaches that X-ray diffraction has become the go-to tool for identifying the crystallinity of polymer materials; the Thermo Scientific specific X-ray diffractometer, in particular, provides expedited data collection times compared to other options (4th paragraph, Pg. 1).
It is prima facie obvious for a person with ordinary skills in the art to incorporate X-ray diffraction measurement taught by Simon instead of using microscopy method in Malakhov to determine the crystallinity, because as Simon points out that this is the go-to-tool for expedited data collection compared to other options. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Rehor (Polypropylene sulfide nanoparticles as drug carriers, Dissertation, 2005, IDS of 01/16/2025, complete version uploaded, PTO-892) in view of Malakhov et al. (WO2009015286, 01/29/2009, PTO-892) as applied to claims 1-3, 5-8 and 11-15 above, further in view of Zepp et al. (US20120114677, 05/10/2012).
Combined teaching of Rehor and Malakhov teaches a microparticle comprising the poly ES/PS ( ethylene sulfide/propylene sulfide) with recurring units of formula (I) as in instant claim 1, and recurring units of X1 is CH3 and X1 is H can be in the molar ratio 1:1 in polymerization to achieve the random copolymer; microparticle diameter for optimal drug compound delivery can be greater than 5 um to up to 500 um, as discussed above and applied to claims 1-8 and 11-15 in detail, and incorporated herein.
Combined teaching of Rehor and Malakhov does not explicitly teach the polymer in the microparticle can further include recurring units of formula (III) with specifics as defined in instant claims 9 and 10.
Zepp throughout the reference directs to drug delivery nanocarriers comprising pharmaceutical materials, e.g., antigens (e.g., [0142-0148]) and teaches compounds and related composition and methods that can be used to raise an antibody response to nicotinic compounds (e.g., Abstract).
Zepp teaches that a compound comprising Formula I (copied below; Claim 1), wherein G and Q can be sulfur, R2, R3, R4 and R5 are independently H or an alkyl group (Claim 1); Zepp further specifies that R4 or R5 comprises H, substituted or unsubstituted C1-C18 alkene or alkane (Claims 5 and 6). When G and Q is sulfur, R2, R3 as H, would result in recurring unit of -S-CH2- (corresponding to X1 is H in instant claim 1); when R2, R3 as alkyl, would result in recurring unit of -S-alkyl-, including -S-CH3- (corresponding to X1 is CH3 in instant claim 1); when R4 or R5 is C1-C18 alkene or alkane, corresponding to instantly claimed recurring unit of formula (III) in instant claim 9, wherein R is -C1-2alkylene-R11 including -CH2-R11 or -CH2CH2-R11, and R11 as C1-4alkyl as instantly claimed (resulting in C2-6 carbon numbers), with overlapping carbon numbers of C1-18 alkyl group in prior art.
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It would have been prima facie obvious for a person with ordinary skills in the art to incorporate the teaching of Zepp to further include the additional recurring unit in the microparticle taught by Rehor and Malakhov, because Zepp shares the general nanoparticle building blocks for the same intended use of drug delivery, Zepp shows the flexibility of substituents that can be introduced into the particle polymerization, an artisan would be motivated to take the advantage of additional suitable building blocks for the microparticle in optimal drug delivery. It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Conclusion
Claims are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DONGXIU ZHANG SPIERING whose telephone number is (703)756-4796. The examiner can normally be reached 7:30am-5:00pm (Except for Fridays).
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/DX.Z./ Examiner, Art Unit 1616
/MONICA A SHIN/ Primary Examiner, Art Unit 1616
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