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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/25/2026 has been entered.
Status of Application
Applicants' arguments/remarks filed 02/25/2026 are acknowledged. Claims 1-3 and 6-20 are examined on the merits within and are currently pending.
Maintained Rejections
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 non-obviousness.
Claims 1-3, 6 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200) and Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265), and Zhao et al. (Zhao et al., Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based
Liposome. International Journal of Nanomedicine 2016:11 5485–5496), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57).
Claim 1,
Zheng et al., teach a monosaccharide-tagged nano-liposome drug delivery system, consisting cholesterol conjugated with a monosaccharide ligand and a phospholipid (Abs, and Table 1, pg. 189).
Kawakami et al. teach a monosaccharide-tagged nano-liposome drug delivery system, consisting cholesterol conjugated with a monosaccharide ligand and a phospholipid (Abs, and Table 1, pg. 260).
Zheng et al. and Kawakami et al. teach monosaccharide-tagged nano-liposome delivery system, but Zheng et al. teach a sialic acid-polyethylenimine-cholesterol (SA-PEI-CH), (sialic acid is a 9-carbon (nonose) monosaccharide acid), while Kawakami teach Gal-C4-Chol, Man-C4-Chol or Fuc-C4-Chol, not cholesterol conjugating glucosamine thought this linker:
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Zhao et al. teach cholesterol conjugating to a compound with a NH-group (N, N-dimethyl propylene diamine (DMAPA)), to form a product, conjugated to cholesterol through this linker:
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Zheng et al., Kawakami et al. and Zhao et al. do not teach glucosamine as monosaccharide.
E Silva et al. teach cholesterol-based glycoconjugates derived from D-galactose and N-acetylglucosamine, were synthesized and incorporated into liposomes. (Abs), where N-acetyl is considered as a linker for cholesterol and glucosamine.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I below.
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With regard to Claim 2, Kawakami et al teach the phospholipid is selected from a group consisting of di-stearyl phospholipid choline (DSPC). (Abs).
With regard to Claim 3, Zheng et al., teach a sialic acid-polyethylenimine-cholesterol (SA-PEI-CH) modified liposomal doxorubicin (DOX-SPCL) (Abs). HSPC/CH/SA-PEI/DiR, nanoliposome size 121.5±1.4nm, and a zeta potential -3.8±0.7 (in which DiR is a lipophilic, near-infrared fluorescent cyanine dye. The dye is useful for labeling cytoplasmic membranes and has been used for near-infrared in vivo imaging). (Table 1, pg. 189). These particle sizes can vary depending on selected phospholipid, monosaccharide-modified-cholesterol and their percentages.
With regard to Claim 6,
Kawakami et al. teach the nano-liposome drug delivery system according to claim 1 comprises an unmodified cholesterol. (Table 1, pg. 260).
Zheng et al. teach the cholesterol drug delivery system also comprises an unmodified cholesterol or just cholesterol. (Table 1, pg. 189).
With regard to Claims 7-8, Zheng et al. teach the liposome drug delivery system comprising cholesterol conjugate a monosaccharide and a phospholipid, and further comprises an anticancer drug doxorubicin (DOX) encapsulated in the liposome (Abs). The TEM image confirmed the near hollow spherical shape of liposomes with the typical structure of a lipid bilayer. (pg. 193, left col., 1st par.). Liposome DOX locked the doxorubicin intra liposome vesicle and insulated drug from external medium. (pg. 193, right col., 1st par.).
With regard to Claim 9, Zheng et al. teach a method of preparing a monosaccharide-tagged nano-liposome drug delivery system according to claim 1, comprising: synthesizing a monosaccharide-conjugated cholesterol (pg. 188, right col., 2nd last par and last par. 2.3.1 Stage 1. PEI-CH and 2.3.2. Stage 2. SA-PEI-CH); preparation of liposomal by solvent injection method, HSPC and cholesterol were dissolved in solvent, dispersed and sonicated. (pg. 189, left col., 2nd par.). The TEM image confirmed the near hollow spherical shape of liposomes with the typical structure of a lipid bilayer. (pg. 193, left col., 1st par.).
With regard to Claim 10, Kawakami et al. teach the preparation of phospholipid (DSPC)/Cholesterol (Chol)/ Galactosylated (Gal) or mannosylated (Man) liposomes DSPC/Chol/Gal-C4-Chol by molar ratios (60:35:5) (pg. 259, section 2, Materials and methods and Table 1, pg. 260).
With regard to Claim 11, Zheng et al. teach a targeted therapeutic nano-liposome, comprising: a monosaccharide-tagged nano-liposome drug delivery system according to claim 1 and doxorubicin is encapsulated efficiently in monosaccharide-cholesterol-liposome (Abs).
Claims 1, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200), Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265) and Zhao et al. (Zhao et al., Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based
Liposome. International Journal of Nanomedicine 2016:11 5485–5496), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57), and further in view of Zhou et al. (Zhou et al., Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity. International Journal of Pharmaceutics 523 (2017) 203–216).
The teachings of Zheng et al., Kawakami et al, Zhao et al., and e Silva et al. are described in claim 1 above.
Zheng et al., teach the targeted therapeutic nano-liposome according to claim 11, wherein the nano-liposome has a size of 103.2 nm (between 80-160 nm), but a zeta potential of -4.5 millivolt not between -10 to -45 millivolt. (Table 1, pg. 189).
Zhou et al., teach the targeted therapeutic nano-liposome according to claim 11, wherein the nano-liposome EPI-SAL has a size of 120.9 nm (between 80-160 nm), and a zeta potential of -17.7millivolt, between -10 to -45 millivolt. (Table 1, pg. 209).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I., and the nanoliposome has a size between 80-160nm and a zeta potential between -10 to -45millivolt, taught by Zhou et al., since they have proven it would be suitable to do so and since particle sizes and zeta potentials can be varied depending on selected phospholipid, linker for monosaccharide with cholesterol and their composition ratios.
Claims 1, 11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200) and Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57), as applied in claim 1, and further in view of Khazanov et al., (Khazanov et al., Physicochemical and Biological Characterization of Ceramide-Containing Liposomes: Paving the Way to Ceramide Therapeutic Application. Langmuir 2008, 24, 6965-6980).
The teachings of Zheng et al., Kawakami et al, and e Silva et al. are described in claim 1, 3, 6 and 7-11 above.
Zheng et al., Kawakami et al, and e Silva et al. do not teach the drug in the nano-liposome described in claims 1 and 11 is ceramide.
Khazanov et al., teach ceramides mediate antiproliferative responses, and it has been proposed that increasing the level of ceramides in cancer cells may have a therapeutic antitumor effect. (Abs). Ceramide-Containing Liposomes: Paving the Way to Ceramide Therapeutic Application. (Title).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I, and to have ceramide as a drug taught by Khazanov et al. since ceramides in cancer cells may have a therapeutic antitumor effect.
Claim 14 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200) and Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265), and Zhao et al. (Zhao et al., Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based Liposome. International Journal of Nanomedicine 2016:11 5485–5496), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57).
Zheng et al. teach a method of preparing a monosaccharide-tagged nano-liposome drug delivery system, comprising: synthesizing a monosaccharide-conjugated cholesterol (pg. 188, right col., 2nd last par and last par. 2.3.1 Stage 1. PEI-CH and 2.3.2. Stage 2. SA-PEI-CH); preparation of liposomal by solvent injection method, in which the modified SA-PEI-CH are added with DOX-CL (pg. 189, left col., section 2.5.1 Preparation of liposomal DOX). The TEM image confirmed the near hollow spherical shape of liposomes with the typical structure of a lipid bilayer. (pg. 193, left col., 1st par.).
Zheng et al., teach a monosaccharide-tagged nano-liposome drug delivery system, consisting cholesterol conjugated with a monosaccharide ligand and a phospholipid (Abs, and Table 1, pg. 189).
Kawakami et al. teach a monosaccharide-tagged nano-liposome drug delivery system, consisting cholesterol conjugated with a monosaccharide ligand and a phospholipid (Abs, and Table 1, pg. 260).
Zheng et al. and Kawakami et al. teach monosaccharide-tagged nano-liposome delivery system, but Zheng et al. teach a sialic acid-polyethylenimine-cholesterol (SA-PEI-CH), while Kawakami teach Gal-C4-Chol, Man-C4-Chol or Fuc-C4-Chol, not cholesterol conjugating glucosamine thought this linker.
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Zhao et al. teach cholesterol conjugating to a compound with a NH-group (N, N-dimethyl propylene diamine (DMAPA)), to form a product, conjugated to cholesterol through this linker.
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Zheng et al., Kawakami et al. and Zhao et al. do not teach glucosamine as monosaccharide.
E Silva et al. teach cholesterol-based glycoconjugates derived from D-galactose and N-acetylglucosamine, were synthesized and incorporated into liposomes. (Abs), where N-acetyl is considered as a linker for cholesterol and glucosamine.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I below.
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Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200) and Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265), and Zhao et al. (Zhao et al., Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based
Liposome. International Journal of Nanomedicine 2016:11 5485–5496), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57) and further in view of Kawakami et al., (Kawakami et al., Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice. Pharmazie 59 (2004) 5).
The teachings of Zheng et al.’s, Kawakami et al. (Bichimica et Biophica Acta), Zhao et al., and e Silva et al. are described in claim 14 above.
Zheng et al. teach liposomes are prepared by mixing phospholipid HSPC and doxorubicin with the ratio given in (Table 1 pg. 189) w/w ratios of DOX-SPCL, which is HSPC/CH/SA-PEI-CH at w/w ratio 3.0/1.0/2.0, (Table 1, pg. 189), where: Dox is doxorubicin, MW 543.52g/mol, is added at a ratio 1g DOX /10g phospholipid (pg. 189, left col., 2nd last par.).
30g HSPC/10g cholesterol/20g SA-PEI-CH and 3g DOXL (pg. 189, left col, 2nd last par.).
HSPC, MW 790g/mol; Cholesterol MW 386.654g/mol; SA-PEI-CH: Sialic Acid MW 309.27g/mol. PEI: Branched polyethylenimine with MW of 1.8 k Da (pg. 188, left col., last par.).
With 0.6 mmol of reactants sialic acid given to react with 0.03 mmol of PEI-CH, (pg. 188, right col, 2nd last and last par.), there may be 1-20 SA per 1 PEI-CH, so its MW can vary from 2502-5825g/mol. With 30g HSPC = 37.97mmol HSPC; 3g DOX = 5.52 mmol DOX;
10g CH = 28.86 mmol CH; and 20g SA-PEI-CH is 7.99-3.43 mmol SA-PEI-CH. With these mmolars, then the drug DOX is mixed with phospholipid, HSPC, and monosaccharide-cholesterol, with unmodified cholesterol, the mmolar percentages of phospholipid can be 47-50%, of the drug can be 7% and of monosaccharide-conjugated cholesterol can be 5-10%. It would be obvious that these percentages can be varied depending on drugs, phospholipids, and monosaccharide-link-cholesterol. Also, in the case of HSPC/CH/SA-PEI-CH/DiR (3.0/1.0/2.0/0.06) ((pg. 189, Table 1), DiR, which can be considered as a different drug, provided the mmolar percentage of the phospholipid to 52-56%.
Kawakami et al. (in Pharmazie) having the plasmid DNA as a drug encapsulated in Mannose-C4-Cholesterol/DOPE cationic liposome at the molar composition 3:2 without unmodified cholesterol (pg. 408, left col., 2nd par.) and with fixed negative charge of plasmid DNA and varied positive charge of Mannose-C4-Cholesterol/DOPE from 1.2, 1.6, 2.3, 3.1 to 4.7, as drug delivery systems for negative plasmid DNA. (pg. 406, Table and Fig. 1), where theoretical charge ratio of cationic lipid/dDNA was calculated as a molar ratio of Man-C4-Chol to a nucleotide unit Iaverage molecular eight 330). (pg. 408, left col., 2nd par.). With higher molar ratios, the Mannose-C4-Cholesterol percentages are increased to have higher positive charge to deliver negative charge plasmid DNA. The calculated molar percentages of Man-C4-Chol are increased up to 17 or 22%.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I, and to have the phospholipid, the monosaccharide-conjugated cholesterol and the drug are mixed in a ratio of 6-25 mmole% of the drug, 52-77 mmole% of the phospholipid, 17-23 mmole% of the monosaccharide-conjugated cholesterol, taught by Zheng and Kawakami, since they have proven it is suitable to do so and since these percentages can be varied depending on liposome compositions and drugs to be delivered with or without unmodified cholesterol.
Claims 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Zheng et al., Exhausting tumor associated macrophages with sialic acid polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy. International Journal of Pharmaceutics 558 (2019) 187–200) and Kawakami et al., (Kawakami et al., Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice. Biochimica et Biophysica Acta 1524 (2000) 258-265), and Zhao et al. (Zhao et al., Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based Liposome. International Journal of Nanomedicine 2016:11 5485–5496), in view of e Silva et al. (e Silva et al., Synthesis of cholesterol-based neoglycoconjugates and their use in the preparation of liposomes for active liver targeting. Carbohydrate Research 465 (2018) 52–57) and further in view of Lukyanov et al., (Lukyanov et al., Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. Journal of Controlled Release Vol. 100, Issue 1, 5 November 2004, Pages 135-144).
The teachings of Zheng et al., Kawakami et al, and e Silva et al. are described in Claims 1, 3, 6, 7-9, 11 and 14 above.
Zheng et al. teach doxorubicin for cancer treatment and the targeted therapeutic nano-liposome with monosaccharide conjugated cholesterol, a pharmaceutically acceptable substrate, carrier or excipient, like phospholipid (pg. 189, left col., 3rd par.), but do not teach the cancer treatment is selected from drug-resistant cancer cell therapy.
Lukyanov et al. teach doxorubicin-loaded long-circulating liposomes doxorubicin, modified with the monoclonal nucleosome (NS)-specific 2C5 antibody (mAb 2C5) that recognizes a broad variety of tumors via the tumor cell surface-bound NSs. (Abs). Several attempts have been made to further improve the anticancer efficiency of DoxilR by targeting it with vector molecules specific to receptors typical for cancer cells. Thus, an attachment of the folate residue to the liposomal surface improved the ability of liposomes to selectively recognize cancer cells that over-express folate receptors. Folate-targeted liposomes loaded with doxorubicin demonstrated a substantial increase in cytotoxicity towards target cells in vitro. Modification with folate promoted the internalization and nuclear delivery of liposomes and allowed to overcome the multiple drug resistance. (pg. 136, left col., 3rd par.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a monosaccharide-tagged nanoliposome drug delivery system, comprising at least a cholesterol conjugated with a monosaccharide and a phospholipid, taught by Zheng et al., and Kawakami et al., where a molecule with NH group can be conjugated with cholesterol through this linker
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, taught by Zhao et al., and the monosaccharide is glucosamine, taught by e Silva et al. since they know these sugars, especially glucose and glucosamine molecules will be highly taken into cells through glucose transporters, including cancer cells, and cholesterol is a good lipid molecule for liposomal drug delivery system, to be conjugated with glucosamine, to form a molecule conjugate cholesterol and glucosamine I,, and to prepare the targeted therapeutic nano-liposome and a pharmaceutically acceptable substrate protein with the anticancer drug consisting of doxorubicin, especially by targeting with folate residue for drug-resistant cancer treatment, taught by Lukyanov et al., since they have proven suitable to do so.
Response to Arguments
Rejections under 35 USC 103
Applicant argues that the proposed combination relies on an overgeneralized and inaccurate
characterization of the references. This rationale fails because the cited references do not actually supply the predicate teachings attributed to them, and the Office Action does not provide a non-hindsight rationale showing how and why a skilled artisan would arrive at the claimed glucosamine and claimed 2-amino linkage with a reasonable expectation of success. Zheng Does Not Teach a "Monosaccharide-Cholesterol Conjugate" Comparable to the Claimed Conjugate. Kawakami Teaches Different Sugars and Underscores That Sugar Identity Matters-It Does Not Render Applicant's Glucosamine Choice Predictable.
Applicant's arguments have been fully considered, but were not persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In addition, the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. In this case Zheng and Kawakami teach different monosaccharide-tagged nano-liposome drug delivery system and Zhao teaches the specific linker and Silva teaches the monosaccharide glucosamine.
Applicant argues that Even If the References Are Considered Together, the Office Action Does Not Establish Motivation and Reasonable Expectation of Success for the Claimed 2-Amino
Linkage. Silva's 1-Position Glycosidic Linkage Does Not Teach or Suggest Applicant's 2-Position (2-Amino) Linkage and Zhao Does Not Provide a Reasonable Pathway or Expectation of Success for Selective N-Conjugation at the 2-Amino Position of Glucosamine.
Applicant's arguments have been fully considered, but were not persuasive. In response to applicant' s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as explained above, Zheng and Kawakami teach different monosaccharide-tagged nano-liposome drug delivery system and Zhao teaches the specific linker and Silva teaches the monosaccharide glucosamine. No one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. The ideas are taught by different references and one with skill in the art can select and combine them. And when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012).
Applicant argues that improper hindsight and lack of a supported rationale under §103. When the references are properly understood, the Office Action's theory requires selecting ( a) Applicant's particular sugar (glucosamine ), (b) Applicant's particular attachment site (2-amino linkage), and ( c) a selective carbohydrate-conjugation pathway that the cited references do not teach. The rejection therefore risks reconstructing the claimed invention using Applicant's disclosure as a roadmap.
Applicant's arguments have been fully considered, but were not persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, as explained above that Zheng and Kawakami teach different monosaccharide-tagged nano-liposome drug delivery system and Zhao teaches the specific linker and Silva teaches the specific monosaccharide glucosamine. One with skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things.
Conclusion
No claim is allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGOC-ANH THI NGUYEN whose telephone number is (571)270-0867. The examiner can normally be reached Monday - Friday 8:00 am.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615