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 .
Detailed Action
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 25-44 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Tsai et al. (US 2005/0019303) in view of Mugabe et al. (Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy, BJUI International, 2008, vol. 103, pp. 978-986 of record), Nag et al. (Pharmaceutics, 2013, 5, 542-569 of record) and Solaro et al. (Targeted Delivery of Protein Drug by Nanocarriers, Materials, 2010, vol. 3, pp. 1928-1980 of record) and further in view of Zale et al. (USP 8,206,747).
Tsai is directed to biodegradable copolymers and polymeric micelle composition comprising the same wherein the micelle possess a hydrophobic core suitable for carrying and delivering hydrophobic drugs (such as paclitaxel - see Example 7) and an outer hydrophilic shell that enables good drug delivery and suitability for use in pharmaceutical applications (see [0015], [0016] and [0039]). Methods of administering the particles are envisaged (see [0049]). The structure of the polymer to formulate the core-shell micelle is a copolymer having the generic formula CSn wherein C is the core block comprising a bioresorbable hydrophobic polyester segment and S is a shell block comprising a hydrophilic polyethylene glycol (PEG) segment covalently linked to the core segment (see claim 1). The hydrophobic polyester segment includes polymers and copolymers synthesized from monomers selected from of lactic and glycolic acid (see claim 8). The hydrophilic PEG segment is to have a molecular weight ranging from 200-10000 g/mol (see claim 6).
Tsai fails to teach the hyperbranched polyglycerol shell.
Mugabe et al. teaches mucoadhesive nanoparticle formulations of paclitaxel comprising unimolecular micelles of 7.2 nm based on hydrophobically derivatized hyperbranched polyglycerols (i.e. PEI-C18-HPG, Fig. 1B) that are dendritic molecules with a hydrophobic core (i.e. hydrophobically modified polyethyleneimine) and hydrophilic shell (i.e. hyperbranched polyglycerol) connected by covalent bonds; wherein the PEI-C18-HPG unimolecular micelles encapsulates the hydrophobic drug molecules inside the core, while the hydrophilic shell keeps the system soluble in water; wherein the surface of PEI-C18-HPG system contains numerous hydroxyl groups (reads on functional groups) that are mucoadhesive in addition to the alkyl chains that can interact with mucin through hydrophobic interactions (Abstract, p. 979, left col., 2nd para., central col., 1st para.; right col., 2nd para.; p. 981, right col., 1st para.; p. 984, central col.; Fig. 1B; Table 1). Mugabe et al. further teaches that polyglycerols are structurally similar to polyethylene glycol (PEG) and polysaccharides and have been shown to be highly biocompatible (p. 979, central col., 1st para.). Mugabe et al. teaches that the outer surface functional groups of the polymers can be easily derivatized with suitable moieties for multivalent interactions to achieve targeted drug delivery (p. 979, left col., 2nd para.). Fig. 1B of Mugabe et al. With regard to the limitation of carrier’, Mugabe et al. teaches 10 mM phosphate buffer (pH = 7.4) as carrier for forming pharmaceutical formulation of paclitaxel loaded PEI-C18-HPG nanoparticles at about 2 wt. % (p. 980, left col., 2nd para.; right col., 1st para.) and the aqueous PBS formulations are suitable for intravesical administration (a type of parenteral administration). Water carrier as taught by Mugabe et al. is a conventional pharmaceutically acceptable carrier for pharmaceutical formulations and aqueous formulation is suitable for topical, topical and parenteral administration.
In further support that hyperbranched polyglycerols are obvious over PEG, Nag is relied upon. Nag is directed to surface engineering of liposomes for achieving stealth behavior. It’s taught that polyethylene glycol (PEG) is widely used as a coating material for delaying the elimination process by the body by endowing them with a stealth functionality but that hyperbranched polyglycerol offers several advantages over PEG such as that they are thermally and oxidatively more stables while maintaining the same level of resistance against protein absorption (see page 549).
Solaro et al. teaches that until now, polyethylene glycol (PEG) is still the most widely used coating material for achieving prolonged circulation in the blood stream, however, successful alternative to PEG for achieving prolonged blood stream circulation has been found and it include polyglycerol (p. 1932, 4th para.).
Thus, taking Mugabe and Nag together, it would have been an obvious modification to the core-shell particle of Tsai to use a hyperbranched polyglycerol as a shell layer, taught by both Mugabe and Nag, in place of PEG with a reasonable expectation for success in rendering the resulting particle with a stealth functionality thereby providing prolonged circulations in blood. See MPEP 2143(I)(B).
The references also do not teach use of tumor targeting agents.
Zale et al. teaches nanoparticle carriers modified with targeting ligand GL2 on the surface as tumor targeted drug delivery carrier, PLA-PEG-GL2 via an amide linker to the PEG chain (claims 9 and 10, Example 24). Zale et al. further teaches that the targeting ligand and nanoparticle conjugate may be prepared using amine modified heterobifunctional polyethylene glycol (NH2-PEG-COOH) (col. 20, line 42-53). The amine modified heterobifunctional polyethylene glycol (NH2-PEG-COOH) taught by Zale et al.. Zale et al. teaches that an increased ligand density may increase target binding (cell binding/target uptake), making the nanoparticle “target specific” (col. 5, line 55-60). Zale et al. further teaches that the surface density of the targeting moiety can be controlled by the ratio of the two or more polymers, i.e. nanoparticle have a density of GL2 targeting moiety at about 219 GL2 per particle (col. 23, line 15-20, 48-56; p. 27, line 13-45; Example 23).
Therefore, based on the guidance provided by Zale et al., it would have been obvious to one of ordinary skill in the art to have utilized a targeting ligand into the hyperbranched polyglycerol of Mugabe et al. for tumor targeted delivery of the drug motivated by the teachings of Zale et al. It would have been further obvious to one of ordinary skill to have controlled the density of the surface targeting functional groups in order to make the nanoparticle tumor targeting specific by following the guidance on controlling ligand density taught by Zale et al.
The references discussed above do not expressly teach that the hydrophobic core is polylactic acid and the surface reactive functional groups as required by instant claims.
Zale et al. teaches nanoparticles of about 60 nm to about 120 nm comprising polylactic acid/polyethylene glycol block copolymer (PLA-PEG) or polylactic acid-g-polyglycolic acid copolymer/polyethylene glycol block copolymer (PLGA-PEG) as carrier for therapeutic agents (e.g. docetaxel) (col. 2, line 1-67; col. 3, line 32-67; col. 5, line 46-67; col. 9, line 1-38; col. 23, line 48-56; Figs. 1-2, 16, 17; Example 6; Table 1). In light of Zale et al., PLGA is an functional equivalent to PLA as nanoparticle carrier for delivery of hydrophobic cancer drug docetaxel as both are biocompatible and biodegradable polyester polymer (Zale et al., col. 8, line 17-67; Examples 18 and 19). Zale et al. further teaches that the addition of PLA in addition to the PLGA-PEG copolymer was found to significantly increase drug load (col. 47, line 10-19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to replace the PLGA hydrophobic core of Mugabe et al. and Solaro et al. with the PLA biodegradable and biocompatible hydrophobic nanoparticle material as taught by Zale et al. because the PLA taught by Zale et al. is a functional equivalent to PLGA as nanoparticle carrier polymer for hydrophobic anti-cancer drug docetaxel with predictable results to produce PLA-PHG encapsulated DTX that are known to be capable of releasing the drug at the desired location to impart anti-cancer effects and are known to show increased drug loading capacity with the addition of PLA polymer (Zale et al., col. 47, line 10-19; Examples 18-19). All the references discussed above teach use of chemotherapeutic agents, such as paclitaxel and docetaxel for targeted site-specific delivery.
Nonstatutory double patenting rejection
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.
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Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,660,828.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof.
The patented claims recite particles comprising (a) a core comprising one or more hydrophobic polymers; and (b) a shell comprising hyperbranched polyglycerol comprising a plurality of surface hydroxyl groups, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymers of the core, wherein a plurality of the surface hydroxyl groups are functionalized with one or more surface reactive functional groups selected from the group consisting of aldehydes, amines, O-substituted oximes, and combinations thereof; and/or targeting moieties are bound to the surface reactive functional groups, wherein the surface reactive functional groups and the targeting moieties render the shell of the particles bioadhesive, and one or more agents selected from the group consisting of therapeutic agents, diagnostic agents, prophylactic agents, nutraceutical agents, and combinations thereof are encapsulated within the particle, associated with the surface of the particle, or a combination thereof. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 12-26 of U.S. Patent No. 10,272,019.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite particles comprising a hydrophobic polymer core and a shell comprising hyperbranched polyglycerol covalently bound to the hydrophobic polymer; wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups or functional groups having tissue targeting moieties bound thereto, wherein the reactive functional groups and the tissue targeting moieties adhere to tissue, cells, or proteins, and one or more agents protecting the skin from ultraviolet light, therapeutic agents, diagnostic agents, prophylactic agents, and combinations thereof encapsulated within the particles, associated with the surface of the particles, or combinations thereof. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of USP 11,364,182.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite particles comprising (a) a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups selected from the group consisting of aldehydes, amines, oximes, O-substituted oximes, isocyanates, isothiocyanates, acyl azides, NHS esters, sulfonyl chlorides, glyoxals, epoxides, oxiranes, carbonates, aryl halides, imidoesters, carbodiimides, anhydrides, fluoropheny] esters, and combinations thereof in an effective amount on the surface of the particles to adhere the particles to tissue. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups selected from the group consisting of aldehydes and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of USP 10,758,459.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite a method of adhering particles to a tissue, the method comprising administering particles comprising: a hydrophobic polymer core and a shell comprising hyperbranched polyglycerol covalently bound to the hydrophobic polymer of the hydrophobic polymer core; wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups, or functional groups having tissue targeting moieties bound thereto, or a combination thereof, wherein the one or more reactive functional groups are bound to the hyperbranched polyglycerol through its vicinal hydroxyl moieties or through a chemical transformation of its vicinal hydroxyl moieties; wherein the one or more reactive functional groups and the functional groups having tissue targeting moieties bound thereto adhere to tissue, cells, or proteins; and one or more agents selected from agents protecting the skin from ultraviolet light, therapeutic agents, diagnostic agents, prophylactic agents, and combinations thereof; wherein the one or more agents are encapsulated within the particles, associated with the surface of the particles, or a combination thereof. Dependent claim 18 recites wherein the particles release different therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof, wherein the therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof are encapsulated within the particles, attached to the surface of the particles, or a combination thereof. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups selected from the group consisting of aldehydes and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of USP11,896,686.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite particles comprising (a) a core comprising one or more hydrophobic or more hydrophobic materials; and (b) a shell comprising hyperbranched polyglycerol, wherein the one or more hydrophobic or more hydrophobic materials is a polymer, wherein the polymer is biodegradable, wherein the biodegradable polymer is an aliphatic polyester, wherein the aliphatic polyester is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and copolymers thereof, wherein the aliphatic polyester is polylactic acid, wherein the hyperbranched polyglycerol is covalently bound to the one or more hydrophobic materials, wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups that adhere to tissue, cells, and/or proteins, wherein the one or more reactive functional groups are selected from the group consisting of aldehydes, amines, O-substituted oximes, and combinations thereof and the particles, further comprising one or more therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups selected from the group consisting of aldehydes and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of USP 11,826,438.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite particles comprising a plurality of amphiphilic polymers comprising a hydrophobic polymer covalently bound to a hyperbranched polyglycerol, wherein the hydrophobic polymer is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and poly(lactic-co-glycolic acid), wherein the hyperbranched polyglycerol has hydroxyl groups converted to aldehydes, wherein the particles comprise a core comprising the hydrophobic polymer covalently bound to the hyperbranched polyglycerol and the hyperbranched polyglycerol forming a shell around the hydrophobic polymer core, and wherein the particles comprise: one or more topoisomerase inhibitors. The patented particles read on the instant particles reciting a core comprising one or more hydrophobic polymers, and (b) a shell comprising hyperbranched polyglycerol having surface exposed functional reactive groups selected from the group consisting of aldehydes and actives as a drug.
Claims 25-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-43 of USP 12,233,140.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims recite a formulation comprising nanoparticles, wherein the nanoparticles comprise: a core comprising a hydrophobic polymer; a shell comprising hyperbranched polyglycerol; and an active agent, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic polymer, wherein the active agent is encapsulated within and/or attached to the surface of the nanoparticles, wherein the nanoparticles are present in an effective amount to treat a brain tumor in a subject in need thereof. The patented claims recite particles comprising: (a) a core comprising one or more polymers; (b) a shell comprising hyperbranched polyglycerol; and (c) one or more nucleic acids, one or more peptides, or a combination thereof; wherein the one or more polymers are more hydrophobic than the hyperbranched polyglycerol; wherein the hyperbranched polyglycerol is covalently bound to the one or more polymers; wherein the hyperbranched polyglycerol at the surface of the particles comprises hydroxyl groups converted to one or more reactive functional groups selected from the group consisting of aldehydes, amines, oximes, and O-substituted oximes; and optionally wherein the particles are modified by attachment of polyethylene glycol to the surface of the particles. The patented claims reciting particles read on the instant claims.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SNIGDHA MAEWALL whose telephone number is (571)272-6197. The examiner can normally be reached Monday thru Friday; 8:30 AM to 5PM.
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/SNIGDHA MAEWALL/Primary Examiner, Art Unit 1612
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