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 .
Applicant’s election without traverse of group I in the reply filed on 5/25/26 is acknowledged.
Claims 24-26 and 30-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/25/26.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-6, 10-15, 419, and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 1 requires for the alkyl chain to have a length sufficient to stabilize the nanoparticle in an aqueous solution for a time period of at least 1 hour, which does not impart any specific structural requirement to the alkyl chain.
The specification does not adequately describe the specific chain length required to have the function of stabilizing the nanoparticle in an aqueous solution for a time period of at least 1 hour.
Claim 10 requires the nanoparticle to comprise any biologically active agent. The specification does not adequately describe the structure required for the agent to be biologically active. Without further description of the structure required for the function, one would not be able to readily envision which agents are or are not biologically active.
Claim 20 requires for the plurality of nanoparticles to be “characterized by” a PDI ranging from 1 to 1.5. The specification does not adequately describe the structure required for the plurality of nanoparticles to be “characterized” by a PDI ranging from 1 to 1.5. It is unclear what specific structure is required in the composition claim for the nanoparticles to be “characterized” in the manner recited.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for each of the recited genuses that have the required functions. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4-6, 10-15, and 19 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Ko et al. (US 2010/0285111 A1).
Ko et al. teach nanoparticles comprising nucleic acids, wherein the nanoparticles comprise a covalent conjugate of a polycation such as polyetheylenimine and phospholipids. The final DNA-containing nanoparticle has a vesicular structure with a polyplex core surrounded by a mixed lipid/PEG-lipid monolayer envelope and offers simple preparation, high loading capacity, and in vivo stability. The nanoparticles have good in vivo stability and a prolonged blood circulation time and can effectively deliver a gene to a biological target such as a tumor (abstract)
Ko et al. teach: [0030] The cationic polymer can be any synthetic or natural polymer bearing at least two positive charges per molecule and having sufficient charge density and molecular size so as to bind to nucleic acid under physiological conditions (i.e., pH and salt conditions encountered within the body or within cells). Suitable cationic polymers include, for example, polyethylene imine, polyornithine, polyarginine, polylysine, polyallylamine, and aminodextran (amine group (instant claim 1) and PEI (instant claim 6).
Ko et al. teach: [0053] Twelve milligrams of the branched PEI (7 .mu.mole) were dissolved in 0.5 ml of chloroform and mixed with five milligrams of the oxidized PC (AzPC Ester, 7 .mu.mole) dissolved in 1 ml of chloroform. Assuming that bPEI has 1:2:1 molar ratio of primary:secondary:tertiary amines, the reaction mixture corresponds to an acid-to-primary amine molar ratio of 1:10, i.e. contains an excess reactive amines (instant claims 1 and 5).
Ko et al. teach: [0029] Micelle-like nanoparticles can have an average diameter in the range from about 10 nm to about 1000 nm. Preferably they have an average diameter in the range from about 10 nm to about 500 nm, more preferably from about 10 nm to about 200 nm, and even more preferably from about 40 nm to about 100 nm or about 50 nm to about 70 nm. The size of MNP is compatible with their ability to enter cells and transfer their nucleic acid content into the cytoplasm of the cell (instant claim 4).
Ko et al. teach: [0031] The hydrophobic portion of an amphipathic lipid can be conferred by the inclusion of non-polar groups including long chain saturated and unsaturated aliphatic hydrocarbon groups and such groups substituted by one or more aromatic, cycloaliphatic or heterocyclic group(s).
Ko et al. teach: [0015] FIGS. 2a-2b show an analysis of MNP formation. (FIG. 2a) Agarose gel electrophoresis of PLPEI/DNA complexes in comparison to PEI/DNA complexes at varying N/P ratios.
Ko et al. teach: [0037] The ratio of cationic polymer to nucleic acid molecules for packaging into nanoparticles of the invention should be adjusted to ensure that all of the nucleic acid is complexed. A gel electrophoretic method for achieving this is described in the examples below. Generally, a ratio of amine to phosphate (N/P) in the range of about 1 to 20 is appropriate. A ratio of about 10 is preferred. The amount of nucleic acid that can be loaded into an individual MNP can vary over a broad range. The nucleic acid content of the completed MNP can be up to 40% by weight, which is much higher than is possible with previously described nucleic acid-containing nanoparticles (instant claim 1).
Ko et al. teach: [0028] A micelle-like nanoparticle 10 according to the present invention contains a core complex encapsulated by a lipid monolayer (see FIG. 1). The core complex 20 contains one or more nucleic acid molecules 30 that are electrostatically bound to one or more molecules of a cationic polymer 40, such as PEI (instant claim 11).
Ko et al. teach: [0009] a novel micelle-like nanoparticle (MNP) loaded with nucleic acid, such as plasmid DNA or siRNA, and a novel approach to constructing the nanoparticle for gene delivery have been developed. A cationic polymer, such as polyethylenimine (PEI), is first conjugated to the distal end of a phospholipid alkyl or acyl chain, resulting in a phospholipid-polyethylenimine (PLPEI) conjugate. The PLPEI is then mixed with a nucleic acid, such as plasmid DNA, oligonucleotides (e.g., antisense oligonucleotides), RNA or a ribozyme, to form complexes having a size in the nanometer range with the structure of a PEI/nucleic acid (PEI/NA) core complex and a phospholipid monolayer envelope (non-covalently bound (instant claim 1). It is noted that a plasmid or an oligonucleotide would meet the instant limitation of “comprising” (open language) 60-500 nucleotides (instant claim 1); and comprises 100 to 350 nucleobases (instant claim 12). The phospholipid contains a hydrophobic domain, wherein the alkyl chain contains carbons (instant claim 1). Instant claim 1 requires for the alkyl chain to have a length sufficient to stabilize the nanoparticle in an aqueous solution for a time period of at least 1 hour, which does not impart any specific structural requirement to the alkyl chain.
Ko et al. teach: [0032] In certain embodiments, a nanoparticle according to the invention contains additional lipids that are not conjugated to a cationic polymer ("non-conjugated lipid" or "non-conjugated phospholipid"). These additional, non-conjugated lipids serve to stabilize and complete the encapsulating lipid monolayer, and also can serve as attachment points for stabilizing moieties (e.g., PEG) or targeting moieties. Non-conjugated lipids can be any of the amphipathic lipids described above, such as phospholipids, and also can include other lipids such as triglycerides and sterols (e.g., cholesterol) (instant claim 10).
Ko et al. recite: 11. The nanoparticle of claim 1, wherein the one or more nucleic acid molecules comprise an oligonucleotide, a DNA molecule, an RNA molecule, or any combination thereof (instant claims 13 and 14).
Ko et al. recite: 12. The nanoparticle of claim 11, wherein the one or more nucleic acid molecules comprise plasmid DNA, RNAi, siRNA, an antisense oligonucleotide, or a ribozyme (instant claim 15).
Ko et al. recite: 13. The nanoparticle of claim 11, wherein the one or more nucleic acid molecules comprise a therapeutic gene.
Ko et al. teach: The complex is formulated for injection [0006] (instant claim 20).
Ko et al. teach: [0043] The nanoparticles and non-viral vectors of the present invention can be administered either alone or as a pharmaceutical composition containing the nanoparticles together with a pharmaceutical carrier such as physiological saline or phosphate buffer, selected in accordance with the route of administration and standard pharmaceutical practice. The pharmaceutical carrier is generally added following particle formation. The concentration of particles in the pharmaceutical formulations can vary widely, i.e., from less than about 0.05%, or about 2.5%, to as much as 10 to 30% by weight.
Ko et al. teach: [0046] For in vitro applications, the delivery of nucleic acids by nanoparticles according to the present invention can be to any cell grown in culture, whether of plant or animal origin, vertebrate or invertebrate, and from any tissue. Contact between the cells and the nanoparticles, when carried out in vitro, takes place in a biologically compatible medium (nanoparticles (plural)) (instant claim 19).
Ko et al. teach: [0044] Pharmaceutical compositions of the present invention may be sterilized by conventional, well known sterilization techniques. Aqueous solutions can be packaged for use or filtered under aseptic conditions and lyophilized, the lyophilized preparation being combined with a sterile aqueous solution prior to administration. The compositions can contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, and calcium chloride. Additionally, the particle suspension may include lipid-protective agents which protect lipids against free-radical and lipid-peroxidative damage on storage. Lipophilic free-radical quenchers, such as alpha-tocopherol, can be used for example (instant claim 19).
Therefore, the claims are anticipated by Ko et al.
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, 2, 4-6, 10-15, 19, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ko et al. (US 2010/0285111 A1), as applied to claims 1, 4-6, 10-15, and 19 above, further in view of Zhu et al. (WO 2015/065773 A1) and Zweers et al. (Journal of Biomedical Materials Research Part B: Applied Biomaterials, 66B, 2, 2003, 559-566).
Ko et al. teach nanoparticles comprising nucleic acids, wherein the nanoparticles comprise a covalent conjugate of a polycation such as polyethyleneimine and phospholipids. The final DNA-containing nanoparticle has a vesicular structure with a polyplex core surrounded by a mixed lipid/PEG-lipid monolayer envelope and offers simple preparation, high loading capacity, and in vivo stability. The nanoparticles have good in vivo stability and a prolonged blood circulation time and can effectively deliver a gene to a biological target such as a tumor (abstract)
Ko et al. teach: [0030] The cationic polymer can be any synthetic or natural polymer bearing at least two positive charges per molecule and having sufficient charge density and molecular size so as to bind to nucleic acid under physiological conditions (i.e., pH and salt conditions encountered within the body or within cells). Suitable cationic polymers include, for example, polyethylene imine, polyornithine, polyarginine, polylysine, polyallylamine, and aminodextran (amine group (instant claim 1) and PEI (instant claim 6).
Ko et al. teach: [0053] Twelve milligrams of the branched PEI (7 .mu.mole) were dissolved in 0.5 ml of chloroform and mixed with five milligrams of the oxidized PC (AzPC Ester, 7 .mu.mole) dissolved in 1 ml of chloroform. Assuming that bPEI has 1:2:1 molar ratio of primary:secondary:tertiary amines, the reaction mixture corresponds to an acid-to-primary amine molar ratio of 1:10, i.e. contains an excess reactive amines (instant claims 1 and 5).
Ko et al. teach: [0029] Micelle-like nanoparticles can have an average diameter in the range from about 10 nm to about 1000 nm. Preferably they have an average diameter in the range from about 10 nm to about 500 nm, more preferably from about 10 nm to about 200 nm, and even more preferably from about 40 nm to about 100 nm or about 50 nm to about 70 nm. The size of MNP is compatible with their ability to enter cells and transfer their nucleic acid content into the cytoplasm of the cell (instant claim 4).
Ko et al. teach: [0031] The hydrophobic portion of an amphipathic lipid can be conferred by the inclusion of non-polar groups including long chain saturated and unsaturated aliphatic hydrocarbon groups and such groups substituted by one or more aromatic, cycloaliphatic or heterocyclic group(s).
Ko et al. teach: [0015] FIGS. 2a-2b show an analysis of MNP formation. (FIG. 2a) Agarose gel electrophoresis of PLPEI/DNA complexes in comparison to PEI/DNA complexes at varying N/P ratios.
Ko et al. teach: [0037] The ratio of cationic polymer to nucleic acid molecules for packaging into nanoparticles of the invention should be adjusted to ensure that all of the nucleic acid is complexed. A gel electrophoretic method for achieving this is described in the examples below. Generally, a ratio of amine to phosphate (N/P) in the range of about 1 to 20 is appropriate. A ratio of about 10 is preferred. The amount of nucleic acid that can be loaded into an individual MNP can vary over a broad range. The nucleic acid content of the completed MNP can be up to 40% by weight, which is much higher than is possible with previously described nucleic acid-containing nanoparticles (instant claim 1).
Ko et al. teach: [0028] A micelle-like nanoparticle 10 according to the present invention contains a core complex encapsulated by a lipid monolayer (see FIG. 1). The core complex 20 contains one or more nucleic acid molecules 30 that are electrostatically bound to one or more molecules of a cationic polymer 40, such as PEI (instant claim 11).
Ko et al. teach: [0009] a novel micelle-like nanoparticle (MNP) loaded with nucleic acid, such as plasmid DNA or siRNA, and a novel approach to constructing the nanoparticle for gene delivery have been developed. A cationic polymer, such as polyethylenimine (PEI), is first conjugated to the distal end of a phospholipid alkyl or acyl chain, resulting in a phospholipid-polyethylenimine (PLPEI) conjugate. The PLPEI is then mixed with a nucleic acid, such as plasmid DNA, oligonucleotides (e.g., antisense oligonucleotides), RNA or a ribozyme, to form complexes having a size in the nanometer range with the structure of a PEI/nucleic acid (PEI/NA) core complex and a phospholipid monolayer envelope (non-covalently bound (instant claim 1). It is noted that a plasmid or an oligonucleotide would meet the instant limitation of “comprising” (open language) 60-500 nucleotides (instant claim 1); and comprises 100 to 350 nucleobases (instant claim 12). The phospholipid contains a hydrophobic domain, wherein the alkyl chain contains carbons (instant claim 1). Instant claim 1 requires for the alkyl chain to have a length sufficient to stabilize the nanoparticle in an aqueous solution for a time period of at least 1 hour, which does not impart any specific structural requirement to the alkyl chain.
Ko et al. teach: [0032] In certain embodiments, a nanoparticle according to the invention contains additional lipids that are not conjugated to a cationic polymer ("non-conjugated lipid" or "non-conjugated phospholipid"). These additional, non-conjugated lipids serve to stabilize and complete the encapsulating lipid monolayer, and also can serve as attachment points for stabilizing moieties (e.g., PEG) or targeting moieties. Non-conjugated lipids can be any of the amphipathic lipids described above, such as phospholipids, and also can include other lipids such as triglycerides and sterols (e.g., cholesterol) (instant claim 10).
Ko et al. recite: 11. The nanoparticle of claim 1, wherein the one or more nucleic acid molecules comprise an oligonucleotide, a DNA molecule, an RNA molecule, or any combination thereof (instant claims 13 and 14).
Ko et al. recite: 12. The nanoparticle of claim 11, wherein the one or more nucleic acid molecules comprise plasmid DNA, RNAi, siRNA, an antisense oligonucleotide, or a ribozyme (instant claim 15).
Ko et al. recite: 13. The nanoparticle of claim 11, wherein the one or more nucleic acid molecules comprise a therapeutic gene.
Ko et al. teach: The complex is formulated for injection [0006] (instant claim 20).
Ko et al. teach: [0043] The nanoparticles and non-viral vectors of the present invention can be administered either alone or as a pharmaceutical composition containing the nanoparticles together with a pharmaceutical carrier such as physiological saline or phosphate buffer, selected in accordance with the route of administration and standard pharmaceutical practice. The pharmaceutical carrier is generally added following particle formation. The concentration of particles in the pharmaceutical formulations can vary widely, i.e., from less than about 0.05%, or about 2.5%, to as much as 10 to 30% by weight.
Ko et al. teach: [0046] For in vitro applications, the delivery of nucleic acids by nanoparticles according to the present invention can be to any cell grown in culture, whether of plant or animal origin, vertebrate or invertebrate, and from any tissue. Contact between the cells and the nanoparticles, when carried out in vitro, takes place in a biologically compatible medium (nanoparticles (plural)) (instant claim 19). Additionally, it would have been obvious to formulate a plurality of the nanoparticles in a composition with a reasonable expectation of a stronger delivery effect than a single nanoparticle.
Ko et al. teach: [0044] Pharmaceutical compositions of the present invention may be sterilized by conventional, well known sterilization techniques. Aqueous solutions can be packaged for use or filtered under aseptic conditions and lyophilized, the lyophilized preparation being combined with a sterile aqueous solution prior to administration. The compositions can contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, and calcium chloride. Additionally, the particle suspension may include lipid-protective agents which protect lipids against free-radical and lipid-peroxidative damage on storage. Lipophilic free-radical quenchers, such as alpha-tocopherol, can be used for example (instant claim 19).
Ko et al. does not disclose the specific quantity of carbon atoms in the alkyl chain. However, it would have been obvious for the alkyl chain to comprise (open language) between 10 and 14 carbon atoms because Zhu et al. teach nanoparticle compositions for the delivery of polynucleotides and teaches that the fatty acid side chains each have 12-20 carbon atoms. Therefore, selection of an alkyl chain comprising 10 atoms is considered to be a matter of design choice and within the normal range known in the art (instant claim 2).
Zhu et al. teach: The phospholipid may be any stable phospholipid with amphipathic properties. For example and without limitation, the phospholipid may be phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphotidylglycerol, or a sphingolipid. The fatty acid chains in the phospholipid may be any length or structure that is compatible that allows the protease-sensitive, polynucleotide - binding molecule to form micelles. For example, the fatty acid chains may have from 9 to 20 carbon atoms, from 10 to 20 carbon atoms, from 12 to 20 carbon atoms, from 14 to 20 carbon atoms, from 16 to 20 carbon atoms, or from 8 to 24 carbons. The fatty acid chains in the phospholipid may be saturated, monounsaturated, diunsaturated, or triunsaturated. The unsaturated fatty acid side chains may have carbon-carbon double bonds in either a cis or trans configuration.
Ko et al. does not teach that the nanoparticles are characterized by a PDI ranging from 1 to 1.5, but does teach that the nanoparticles have a narrow size distribution [0015]. It would have been obvious for the nanoparticle formulation of Ko et al. to have a PDI ranging from 1 to 1.5 because Zweers et al. teach that nanoparticles based on biodegradable polymers can function as vehicles with controlled drug-release properties and that control over particle size is of great importance. Zweers et al. teach that the particles are between 100 and 400 nm in size (abstract). Zweers et al. teach that polydispersity index is a dimensionless measure of the broadness of the size distribution and that the polydispersity index of the polymer composition ranges from 1.42 to 2.09 (page 561). Zweers et al. teach that larger particles have a higher PDI (page 563). Therefore, it was routine in the art to design the size and size distribution based upon a PDI in the recited range (instant claim 20).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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