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 . Claims included in prosecution are claims 1-2, 4-5, 8, 10, 15, and 17-22.
Previous Rejections
Applicants' arguments in the Request for Continued Examination, filed Jun. 19, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
1. Claim(s) 1-2, 4-5, 8, 10, 15, 18, and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bilgicer et al. (US 2018/0263909, Sep. 20, 2018) (hereinafter Bilgicer) in view of Chang et al. (US 2019/0194281, Jun. 27, 2019) (hereinafter Chang) and Wamhoff et al. (US 2015/0111240, Apr. 23, 2015) (hereinafter Wamhoff).
Bilgicer teaches pharmaceutical compositions comprising liposomes that contain two or more anticancer drugs (Abstract). The liposome comprises: a) a phospholipid; b) a pegylated lipid; c) an aqueous core (satisfies claim 20); and d) at least two different drug components, wherein the drug components comprise a covalently-linked drug conjugated lipid, an encapsulated drug, or a combination thereof, and wherein the drug components are anticancer drugs (¶ [0008-0012]). The diameter of the liposome is about 5 nm to about 200 nm (satisfies claim 15) (¶ [0013]). The drug combinations may include a proteasome inhibitor and a histone deacetylase inhibitor (HDAC inhibitor) wherein the two different drug components are present in a synergistic ratio (¶ [0014]). Suitable proteasome inhibitors for use include bortezomib (satisfies proteasome-inhibiting compound of claim 1 & 4). Suitable HDAC inhibitor include vorinostat (¶ [0015]). Suitable pegylated lipids include DSPE-PEG2000 (¶ [0018]). In one embodiment, the liposome comprises at least one encapsulated drug component and the encapsulated drug component is localized to the aqueous core. The encapsulated drug can also be located in the lipid bilayer of the liposome. Other drugs and various drug conjugates may also be located in the lipid bilayer and/or they can be localized, at least in part, to the aqueous core (satisfies active disposed within fluid filled center or within lipid bilayer of claim 1) (¶ [0019]). The liposome can be administered as a composition for the treatment of multiple myeloma (satisfies composition of claim 1) (¶ [0027]). The liposome can comprise a combination of one or more phospholipids, an optional lipid that is not a phospholipid, such as cholesterol, pegylated lipids, or a combination thereof (¶ [0073]). The addition of pegylated lipids to the liposomal nanoparticle significantly reduces toxicity and the potential for rejection by the host's immune system (¶ [0087]). The composition may be in the form of a capsule wherein the capsule may include a liquid carrier for the composition (satisfies claim 21) (¶ [0095]). A loading efficiency of more than 95% was achieved for both drugs (satisfies claim 5) (¶ [0119]).
Bilgicer differs from the instant claims insofar as not disclosing wherein the liposome contains a targeting moiety such as PSGL-1 coupled to the outer surface.
However, Chang teaches the delivery of an agent to autophagic and/or apoptotic cells and tissues through a vesicle with an engineered protein expressed on or conjugated to the surface thereof (¶ [0001]). The invention comprises one or more lectins or a fragment thereof expressed or conjugated to the surface of the vesicle and optionally an agent (¶ [0005]). Particular embodiments of the vesicle include liposome and micelle (¶ [0006]). Suitable lectins or fragments thereof include P-selectin-ligand-1 (PSGL-1) (¶ [0007]). Suitable agents to be delivered include antitumor drugs (¶ [0012]). The delivery of an agent or a therapeutic agent with the vesicle to apoptotic cells is directed to a disease associated with apoptosis alteration such as cancer (¶ [0075]).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified Bilgicer’s liposome to include a targeting moiety such as PSGL-1 motivated by the desire to achieve a liposome that specifically targets cancer affected cells in order to directly deliver antitumor actives to said affected cells as taught by Chang.
The combined teachings of Bilgicer and Chang do not disclose wherein the composition comprises a BMME-disrupting agent such as Y27632.
However, Wamhoff discloses that suitable anticancer agents include proteasome inhibitors such as bortezomib, HDAC inhibitors such as vorinostat, rho kinase inhibitors such Y27632, and combinations thereof (¶ [0242]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Bilgicer discloses wherein the liposome may contain another anticancer agent in addition to bortezomib. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the composition of Bilgicer in view Chang to comprise Y27632, since it is a known anticancer agent as taught by Wamhoff.
Alternatively, it is obvious to replace one component for another equivalent component if it is recognized in the art that the two components are equivalent and is not based on the Applicant disclosure. See MPEP 2144.06. Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have formulated Bilgicer’s composition to comprise Y27632 in place of vorinostat because they are taught as equivalents by Wamhoff.
Regarding the encapsulation efficiency recited in instant claim 10 (i.e., about 40%-60%), in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). As discussed above, Bilgicer’s liposome achieved more than 95% loading efficiency for both drugs. Accordingly, because the encapsulation efficiency recited in the instant claims lie inside the loading efficiency disclosed by Bilgicer, the loading efficiency disclosed by Bilgicer meets the instantly recited limitations.
Regarding claim 18, as discussed above, Bilgicer’s liposome may comprise lipids such as cholesterol along with pegylated lipids such as DSPE-PEG2000 (i.e., satisfies “any combination thereof”).
Regarding the dosage recited in instant claim 22, 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. See MPEP 2144.05(II)(A). As discussed above, Bilgicer’s liposomes are therapeutic where they contain anticancer agents, which makes their dosage a result effective variable, since dosage directly impacts the therapeutic effect. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed dosage of 2 mg/mL to yield the desired anticancer (i.e., therapeutic) effect.
Therefore, the combined teachings of Bilgicer, Chang, and Wamhoff render obvious claims 1-2, 4-5, 8, 10, 15, and 20-22.
2. Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bilgicer et al. (US 2018/0263909, Sep. 20, 2018) (hereinafter Bilgicer) in view of Chang et al. (US 2019/0194281, Jun. 27, 2019) (hereinafter Chang) and Wamhoff et al. (US 2015/0111240, Apr. 23, 2015) (hereinafter Wamhoff) and further in view of Vogel et al. (Scientific Reports | 7: 17479, Dec. 12, 2017) (hereinafter Vogel).
The teachings of Bilgicer, Chang, and Wamhoff are discussed above.
The combined teachings of Bilgicer, Chang, and Wamhoff do not disclose wherein the zeta potential of the liposome is at least 28 mV.
However, Vogel discloses that zeta potential, which is indicative of the particle surface charge, is an important and widely used characterization method of nanometer-sized objects in pharmaceuticals and liposomes. Zeta potential values of typically ±30 mV are representative of stabilized particles (Introduction, Par. 2).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified Bilgicer’s liposome to have a zeta value of around 30 mV motivated by the desire to achieve a stable liposome as taught by Vogel.
Therefore, the combined teachings of Bilgicer, Chang, Wamhoff, and Vogel render obvious claim 17.
3. Claim(s) 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bilgicer et al. (US 2018/0263909, Sep. 20, 2018) (hereinafter Bilgicer) in view of Chang et al. (US 2019/0194281, Jun. 27, 2019) (hereinafter Chang) and Wamhoff et al. (US 2015/0111240, Apr. 23, 2015) (hereinafter Wamhoff) and further in view of Unger et al. (US 2016/0000943, Jan. 7, 2016) (hereinafter Unger).
The teachings of Bilgicer, Chang, and Wamhoff are discussed above.
While the combined teachings of Bilgicer, Chang, and Wamhoff disclose the use of cholesterol and DSPE-PEG2000, they do not disclose wherein the composition comprises DPPC and DSPE-PEG(2000)-succinyl.
However, Unger teaches a phospholipid composition (¶ [0002]). Suitable phospholipids for use include dipalmitoylphosphatidylcholine or DPPC (¶ [0028]). Suitable pegylated lipids which may be employed include DSPE-PEG(2000) Succinyl (¶ [0054]). In certain examples, the composition may be used to target cancer cells (¶ [0094]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Bilgicer discloses wherein the liposome may contain phospholipids and pegylated lipids. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the composition of Bilgicer to comprise DPPC and DSPE-PEG(2000) Succinyl, since they are known phospholipids and pegylated lipids used in compositions to treat cancer as taught by Unger.
Regarding the ratio recited in instant claim 19, 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. See MPEP 2144.05(II)(A). As discussed above, the lipid bilayer of Bilgicer’s liposome is formed from lipids, phospholipids, and pegylated lipids, which makes ratios thereof a result effective variable, since the lipid bilayer composition would directly impact the bilayers physical properties. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed ratio of 6:3:0.5:0.5 to yield the desired lipid bilayer composition.
Therefore, the combined teachings of Bilgicer, Chang, Wamhoff, and Unger render obvious claims 18-19.
Response to Arguments
Applicant’s arguments filed 4/24/26 have been fully considered but were not found to be persuasive.
Regarding Applicant’s arguments that the teachings of Bilgicer, Chang, Wamhoff, and Vogel allegedly fail to disclose or suggest all of the elements of independent clam 1, the Examiner submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See MPEP § 7.37.13. As discussed above, claim 1 is rendered prima facie obvious over the combined teachings of Bilgicer, Chang, and Wamhoff, because it would have been obvious for one of ordinary skill in the art to modify the liposome of Bilgicer to comprise a targeting moiety such as PSGL-1 to achieve a liposome that specifically targets cancer affected cells in order to directly deliver antitumor actives to said affected cells as taught by Chang. It would have been further obvious for one of ordinary skill in the art to modify the liposome of Bilgicer in view of Chang to comprise Y27632, since it is a known anticancer agent as taught by Wamhoff. Alternatively, it would have been obvious for one of ordinary skill in the art to have formulated Bilgicer’s composition to comprise Y27632 in place of vorinostat because they are taught as equivalents by Wamhoff.
Moreover, Applicant is reminded that a skilled artisan is not an automaton, but a person having ordinary skill in the art and is capable of fitting teachings of multiple prior art documents together like pieces of a puzzle. See MPEP § 2143.03. Therefore, a skilled artisan would be highly capable of combining the teachings of Bilgicer, Chang, and Wamhoff to arrive at the claimed composition/liposome. Since the cited prior art teaches each of the instantly recited limitations, a prima facie case of obviousness is established. Accordingly, Applicant’s argument is unpersuasive and the obviousness rejection is maintained.
Applicant alleges that the prior art of record fails to disclose a composition comprising a proteasome-inhibiting compound. However, as noted by Applicant’s arguments at Pg. 7, and as discussed above, Bilgicer’s liposome comprises a proteasome inhibitor. Specifically, said proteasome inhibitor may be bortezomib as instantly claimed. As such, the prior art does indeed disclose a composition comprising a proteasome-inhibiting compound.
Regarding Applicant’s argument that Chang does not cure the alleged deficiencies of Bilgicer, the Examiner submits that Chang cures any alleged deficiencies of Bilgicer where Chang provides strong motivation to utilize PSGL-1 as a targeting moiety for antitumor/anticancer formulations, as discussed above.
Regarding Applicant’s argument that Wamhoff does not cure the alleged deficiencies of Bilgicer, the Examiner submits that Wamhoff cures any alleged deficiencies of Bilgicer where Wamhoff discloses that Y27632 is a known anticancer agent and is an equivalent to vorinostat.
Regarding Applicant’s argument that Vogel does not cure the alleged deficiencies of Bilgicer, the Examiner submits that Vogel cures any alleged deficiencies of Bilgicer where Vogel provides strong motivation to utilize a zeta potential of ±30 mV, as discussed above.
In light of the foregoing, the Examiner does not find Applicant’s arguments to be persuasive and the rejection is maintained.
Conclusion
Claims 1-2, 4-5, 8, 10, 15, and 17-22 are rejected.
Claims 23-27 are withdrawn.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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/A.A./Examiner, Art Unit 1612
/LEZAH ROBERTS/Primary Examiner, Art Unit 1612
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