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 the Claims
Claims 1-16 are pending and currently under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statement (IDS) filed on 09/24/2024 and 01/08/2025 are attached to the instant Office action. The submission 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 1-16 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 phrase “comprising or consisting of”. This language renders the claim indefinite because it is unclear whether the claim is closed or open, as comprising could include ‘more’ while ‘consisting of’ cannot, therefore the alternative language causes uncertainty.
Claim 5 recites the phrase “a N/P ratio”. This language renders the claim indefinite because it is wholly unclear what a N/P ratio is and Applicants have not given a definition in the instant specification.
Claims 6 and 14 recites the phrase “further comprising at least one additive”. This language renders the claim indefinite because claims 6 and 14 depend from claim 1 which recites “comprising or consisting of”, therefore claim 6 is broader than the closed “consisting of” language which does not include an additive when the alternative is selected.
Claims 8 and 9 recites the phrase “at least one additive”. This language renders the claim indefinite because claims 8 and 9 depend from claim 1 which recites “comprising or consisting of”, therefore claims 8 and 9 are broader than the closed “consisting of” language which does not include an additive when the alternative is selected.
Claims depending from rejected claims have also been rejected because they incorporate
all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness
concerns outlined above.
Claim Interpretation
The Examiner is interpretating the claims to read on “a polynucleotide delivery particle comprising”, for which the prior art cited meets the comprising language as instantly claimed.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 1-8, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Fahmy et al. (US20180200336A1, Published 07/19/2018) as evidenced by Held et al. (The Column, Published 12-07-2015, Volume 11, Issue 22).
Applicant’s invention
The Applicants claims are drawn to a polynucleotide delivery particle, comprising a) at least one poly(lactic-co-glycolide); b) at least one cationic surfactant; and c) at least one polynucleotide; wherein the poly(lactic-co-glycolide) has a weight average molecular weight Mw of 1000 to 9500 g/mol measured via gel permeation chromatography using polystyrene standards and chloroform.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1, 3, and 15, Fahmy teaches a nanolipogel comprising
a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell;
wherein the polymeric matrix core has at least one host molecule dispersed therein or covalently bound thereto, wherein the host molecule is reversibly associated with a first active agent; and wherein the nanolipogel includes at least one additional active agent provided in the polymeric matrix core or in or on the lipid shell; for controlled release of said first active agent and said at least one additional active agent from the nanolipogel (claim 17). Fahmy also teaches the polymeric matrix is formed from an aliphatic polyester, wherein the polyester is poly(lactide-co-glycolide) (PLGA) (paragraph [0053]). Fahmy also teaches nanolipogels include a liposomal shell composed of one or more concentric lipid monolayers or lipid bilayers such as suitable cationic lipids (i.e., cationic surfactant) including N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) (i.e., 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride) (paragraph [0098]). Fahmy further teach the disclosed compositions can be for cell transfection of polynucleotides (paragraph [0142]), wherein the particular polynucleotide delivered by the nanolipogel can be selected by one of skill in the art depending on the condition or disease to be treated (paragraph [0143]). Fahmy continues to teach that “Molecular weight” as used herein, generally refers to the relative average chain length of the bulk polymer; wherein In practice, molecular weight can be estimated or characterized using various methods including gel permeation chromatography (GPC) or capillary viscometry (paragraph [0033]). Fahmy also teaches the polymeric matrix may be formed from polymers having a variety of molecular weights, so as to form nanolipogels having properties, including drug release rates, optimal for specific applications. Generally, the polymers which make up the polymeric matrix possess average molecular weights of about 500 Da and 50 kDa (i.e., 500g/mol to 50,000g/mol) (paragraph [0051]). As evidenced by Held et al., polystyrenes (PS) are the most commonly used reference standards in gel permeation chromatography/size-exclusion chromatography (GPC/SEC) for nearly all organic GPC/SEC separations including high temperature GPC (abstract).
Regarding claim 2, Fahmy teaches capillary viscometry provides estimates of molecular weight as the inherent viscosity determined from a dilute polymer solution using a particular set of concentration, temperature, and solvent conditions (paragraph [0033]).
Regarding claim 4, Fahmy teaches the particular polynucleotide delivered by the nanolipogel can be selected by one of skill in the art depending on the condition or disease to be treated (paragraph [0143]).
Regarding claim 5, Fahmy teaches the disclosed compositions can be used in a method of delivering active agents to cells in vivo. In some in vivo approaches, the compositions are administered to a subject in a therapeutically effective amount (paragraph [0135]). Fahmy also teaches release rates are modulated by varying the polymer to lipid ratio from 0.05 to 5.0 (paragraph [0112]).
Regarding claims 6 and 14, Fahmy teaches in preferred embodiments, the lipid shell is formed from a combination of more than one lipid, wherein the lipids can be neutral, anionic or cationic lipids at physiologic pH (paragraph [0096]). Fahmy also teaches Such compositions can include diluents sterile water, buffered saline of various buffer content (e.g., Tris-HCl, acetate, phosphate) and solubilizing agents (e.g., TWEEN® 20, TWEEN® 80 also referred to as polysorbate 20 or 80) (i.e., additives) (paragraph [0124]).
Regarding claim 7, Fahmy teaches FIGS. 1C-1G show nanolipogel characterization. Mean diameter and polydispersity index are representative of 2 lots of each nanolipogel type (n=10 measurements per sample) (paragraph [0018]). Fahmy also teaches dynamic light scattering analysis revealed a mean diameter of 120 nm and polydispersity index of 0.2 (paragraph [0205]).
Regarding claim 8, Fahmy teaches nanolipogels have an out shell which encapsulates components so that they are not exposed until desired (paragraph [0037]).
Regarding claims 11 and 13, Fahmy teaches the nanolipogels can be applied topically. Topical administration can include application to the oral (sublingual, buccal) mucosa (paragraph [0126]).
Regarding claims 12 and 16, Fahmy teaches Pharmaceutical compositions can be for administration by parenteral (intramuscular, intraperitoneal, intravenous (IV) or subcutaneous injection) (paragraph [0118]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Fahmy does not disclose a single embodiment or example where every limitation recited in the instant claims is taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art because
Fahmy teaches all of the claimed elements. It would have been prima facie obvious at the time
of filing to have a polynucleotide delivery particle, comprising a) at least one poly(lactic-co-glycolide); b) at least one cationic surfactant; and c) at least one polynucleotide;
wherein the poly(lactic-co-glycolide) has a weight average molecular weight Mw of 1000 to 9500 g/mol measured via gel permeation chromatography using polystyrene standards and chloroform because Fahmy teaches these elements as components of their invention.
With regards to claim 2, wherein the at least one poly(lactic-co-glycolide) has an inherent viscosity of 0.05 to 0.25 dl/g measured via viscometry, it would have been prima facie obvious to one of ordinary skill in the art to optimize the inherent viscosity of the poly(lactic-co-glycolide). Fahmy teaches capillary viscometry provides estimates of molecular weight as the inherent viscosity determined from a dilute polymer solution using a particular set of concentration, temperature, and solvent conditions (paragraph [0033]). Therefore, it would have been obvious to optimize the inherent viscosity of the poly(lactic-co-glycolide) by routine experimentation using the teaching of Fahmy as a starting point to achieve the desired results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
With regards to claim 4, it would have been prima facie obvious to one of ordinary skill in the art to have a single or double-stranded polynucleotide as Fahmy’s polynucleotide. One would have understood in view of Fahmy that the particular polynucleotide delivered by the nanolipogel can be selected by one of skill in the art depending on the condition or disease to be treated (paragraph [0143]). Therefore, it would have been obvious to one of ordinary skill in the art to have a single stranded or multi-stranded polynucleotide because Fahmy teaches that depending on the condition or disease to be treated, the particular polynucleotide (i.e., single-stranded or multi-stranded) can be selected.
With regards to claim 5, wherein a N/P ratio of the at least one cationic surfactant to the at least one polynucleotide ranges from 1:1 to 50:1; and/or ii) a molar ratio of the at least one poly(lactic-co-glycolide) to the at least one polynucleotide ranges from 1:1 to 200:1, it would have been prima facie obvious to one of ordinary skill in the art to optimize the molar ratios. Fahmy teaches the disclosed compositions can be used in a method of delivering active agents to cells in vivo. In some in vivo approaches, the compositions are administered to a subject in a therapeutically effective amount (paragraph [0135]). Fahmy also teaches release rates are modulated by varying the polymer to lipid ratio from 0.05 to 5.0 (paragraph [012]). Therefore, it would have been obvious to optimize the molar ratios by routine experimentation using the teaching of Fahmy as a starting point to achieve the desired results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Fahmy et al. (US20180200336A1, Published 07/19/2018) in view of Elzoghby et al. (Biomaterials., Published 2020 Dec; 263:120355) as evidenced by Held et al. (The Column, Published 12-07-2015, Volume 11, Issue 22).
Applicant’s invention
Fahmy renders obvious all the limitations of claim 1. Applicants claim 9 further adds the limitations wherein the outer coating layer comprises a human lactoferrin protein or a fragment thereof or the at least one additive absorbed to the surface of the polynucleotide delivery particle is a human lactoferrin protein or a fragment thereof.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 9, Fahmy teaches nanolipogels have an out shell which encapsulates components so that they are not exposed until desired (paragraph [0037]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Fahmy does not teach wherein the outer coating layer comprises a human lactoferrin protein or a fragment thereof or the at least one additive absorbed to the surface of the polynucleotide delivery particle is a human lactoferrin protein or a fragment thereof. However this deficiency is cured by Elzoghby.
In the analogous art of nanomedicine, Elzoghby teaches lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier (abstract). Elzoghby also teaches Lf possesses a wide array of different functions including anticancer activity, anti-inflammatory, a potential role in bone health preservation and cognitive function improvement in patients with Alzheimer's disease (Pharmacological activities of lactoferrin section). Incorporation of bLf into liposomes was found to improve its anti-inflammatory action following its oral or intra-articular administration by improving its resistance to gastric digestion and hence increasing its intestinal absorption. Moreover, liposomal Lf showed higher cytotoxicity against cancer cells by increasing its intracellular accumulation and protecting from lysosomal or proteasomal degradation (4.3 Liposomes section).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have the outer coating layer comprises a human lactoferrin protein or a fragment thereof in Fahmy’s nanolipogel comprising a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell. Fahmy teaches nanolipogels have an out shell which encapsulates components so that they are not exposed until desired (paragraph [0037]), wherein active agents can be dispersed within the hydrogel matrix, associated with one or more host molecules, dispersed within the liposomal shell, covalently attached to the liposomal shell, and combinations thereof (paragraph [0039]). The artisan of ordinary skill would have been motivated to have a human lactoferrin protein on the outer coating layer because Elzoghby teaches lactoferrin (Lf) possesses a wide array of different functions including anticancer activity, anti-inflammatory, a potential role in bone health preservation and cognitive function improvement in patients with Alzheimer's disease (Pharmacological activities of lactoferrin section). Incorporation of bLf into liposomes was found to improve its anti-inflammatory action following its oral or intra-articular administration by improving its resistance to gastric digestion and hence increasing its intestinal absorption. Moreover, liposomal Lf showed higher cytotoxicity against cancer cells by increasing its intracellular accumulation and protecting from lysosomal or proteasomal degradation (4.3 Liposomes section). The skilled artisan would have had a reasonable expectation of success because Fahmy teaches active agents can be dispersed within the hydrogel matrix, associated with one or more host molecules, dispersed within the liposomal shell, covalently attached to the liposomal shell, and combinations thereof, wherein the active agents can include anti-inflamatories, anti-cancer agents, etc. (paragraph [0086]) and Elzoghby teaches lactoferrin (Lf) possesses a wide array of different functions including anticancer activity, anti-inflammatory, wherein incorporation of bLf into liposomes was found to improve its anti-inflammatory action following its oral or intra-articular administration by improving its resistance to gastric digestion and hence increasing its intestinal absorption.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Fahmy et al. (US20180200336A1, Published 07/19/2018) in view of Mukherjee et al. (Int J Nanomedicine. Published 2019;14:1937-1952 )as evidenced by Held et al. (The Column, Published 12-07-2015, Volume 11, Issue 22).
Applicant’s invention
Fahmy renders obvious all the limitations of claim 1. Applicants claim 10 further adds the limitations of a method of forming the polynucleotide delivery particle according to claim 1, wherein the polynucleotide delivery particle is formed by a nanoprecipitation or a nanoemulsion method.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 10, Fahmy teaches a nanolipogel comprising a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell; wherein the polymeric matrix core has at least one host molecule dispersed therein or covalently bound thereto, wherein the host molecule is reversibly associated with a first active agent; and wherein the nanolipogel includes at least one additional active agent provided in the polymeric matrix core or in or on the lipid shell; for controlled release of said first active agent and said at least one additional active agent from the nanolipogel (claim 17).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Fahmy does not teach a method of forming the polynucleotide delivery particle according to claim 1, wherein the polynucleotide delivery particle is formed by a nanoprecipitation or a nanoemulsion method. However this deficiency is cured by Mukherjee et al.
In the analogous art of lipid–polymer hybrid nanoparticles, Mukherjee teaches Lipid–polymer hybrid nanoparticles (LPHNPs) are next-generation core–shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer (abstract). Mukherjee also teaches the limitation of the two-step method is that preparing polymeric NPs and lipid vesicles separately makes the process inefficient in terms of energy and time spent. The commonly available and more efficient alternative is a one-step method. Preformed lipid vesicles and polymeric NPs are not prerequisites for the one-step method. The method solely requires mixing of lipid and polymer solutions that subsequently tend to self-assemble to form LPHNPs. The most common processes are nanoprecipitation and/or ESE, both of which are often implemented for the production of nonhybrid polymeric NPs (One-Step method section). Mukherjee also teaches that one-step method is preferred over the two-step method due to its simplicity. Subcategorically, within the realm of one-step method, despite higher content loading in the ESE method, nanoprecipitation is favored as it can produce sub-100 nm sized particles. Nanoprecipitation, thus, has advanced to large-scale production by a continuous high-throughput microfluidic process. (Future possibilities section).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use the method of nanoprecipitation to form Fahmy’s nanolipogel comprising a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell. Fahmy teaches a nanolipogel comprising a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell (claim 17). The artisan of ordinary skill would have been motivated to use the method of nanoprecipitation because Mukherjee also teaches the limitation of the two-step method is that preparing polymeric NPs and lipid vesicles separately makes the process inefficient in terms of energy and time spent. The commonly available and more efficient alternative is a one-step method. Preformed lipid vesicles and polymeric NPs are not prerequisites for the one-step method. The method solely requires mixing of lipid and polymer solutions that subsequently tend to self-assemble to form LPHNPs. The most common processes are nanoprecipitation and/or ESE, both of which are often implemented for the production of nonhybrid polymeric NPs (One-Step method section). Mukherjee also teaches that one-step method is preferred over the two-step method due to its simplicity. Subcategorically, within the realm of one-step method, despite higher content loading in the ESE method, nanoprecipitation is favored as it can produce sub-100 nm sized particles. Nanoprecipitation, thus, has advanced to large-scale production by a continuous high-throughput microfluidic process. (Future possibilities section). The skilled artisan would have had a reasonable expectation of success because Fahmy teaches a nanolipogel comprising a polymeric matrix core formed of one or more polymers or copolymers and a lipid shell (claim 17) and Mukherjee teaches Lipid–polymer hybrid nanoparticles (LPHNPs) are next-generation core–shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer (abstract).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
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