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 .
Election/Restrictions
Applicant’s election without traverse of Group I, TLR7 agonist combined with at least one more API that modulates an immune response (Genus A) and release from the composition after administration to a human or animal body at comparable rates (Genus B) in the reply filed on 6/21/2024 is acknowledged.
Claims 19-27, 29-32, 34, 36-37, and 40-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group I and species of Genus A & B, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/21/2024. In the reply filed on 6/21/2024, Applicant did not elect a species from Genus C. Applicant will be required to elect a species in the future as prosecution advances.
Status of Claims
Cancelled: 5, 7-9, 15
Withdrawn: 19-27, 29-32, 34, 36-37, 40-43
New: 50-51
Examined Herein: 1-4, 6, 10-14, 16-18, 28, 33, 35, 38-39, 44-51
Priority
Priority to SE1950699-7 filed on 6/12/2019 and PCT/EP2020/066403 filed on 6/12/2020 is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/28/2022 is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
examiner.
Drawings
The drawings filed on 12/13/2021 are accepted.
Withdrawn Rejections
The rejection of claims 13 and 14 under 35 U.S.C. 112(b) is hereby withdrawn in view of Applicant’s amendments to claims 13 and 14, which remove the trademark/trade name Lipiodol, thereby rendering the rejection moot.
The rejection of claim 14 under 35 U.S.C. 112(b) is hereby withdrawn in view of Applicant’s amendments to claim 14, which specify the unit of measurement for LacBen:Ethyl-palmitate: EtOH and CLA-8:SuBen:GTO:EtOH, thereby rendering the rejection moot.
The rejection of claims 1, 2, 4, 6, 10-12, 16-18, 28, 35, 38, 39, and 44-46 under 35 U.S.C. 103 over Andresen and Albrechtsen is hereby withdrawn in view of Applicant’s amendments to claim 1.
Claim Objections
Applicant is advised that should claim 46 be found allowable, claim 51 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 45 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 1 recites that the organic solvent is an alcohol, sulfoxide, carbonate, ester, ketone, amide, glycol, polyol, or a mixture thereof. Claim 45 recites that the organic solvent is tert-butyl-methyl-ether, ethyl ether, heptane, and pentane. However, none of these compounds are an alcohol, sulfoxide, carbonate, ester, ketone, amide, glycol, polyol, or a mixture thereof. Therefore, it is unclear whether the organic solvent is indeed limited to solvents which fall within the recited class of compounds, or the organic solvent is not limited, and may extend to other classes of compounds including ether and alkane. Appropriate correction and/or clarification is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 45 rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In the present case, claim 1 recites that the organic solvent is an alcohol, sulfoxide, carbonate, ester, ketone, amide, glycol, polyol, or a mixture thereof. Claim 46 recites that the organic solvent is tert-butyl-methyl-ether, ethyl ether, heptane, and pentane. Therefore, claim 45 fails to further limit the subject matter of claim 1, as it recites organic solvents that fall within additional classes of compounds including ether and alkane.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claims 1, 2, 4, 6, 10, 11, 12, 16, 17, 18, 28, 33, 35, 38, 39, 44-46, 50, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Andresen (US 2018/0325819 A1, Published 11/15/2018), in view of Chung (US 2008/0249296 A1, Published 10/9/2008).
With respect to claim 1, Andresen discloses a composition comprising;
A) a hydrophobic saccharide, lactose acetate:propionate (1:1) (78% w/w)
B) a solvent, propylene carbonate (5% w/w) and EtOH (10% w/w)
C) a lipid oil, glycerol trioctanoate (5% w/w); and
D) an API, imiquimod. [Andresen, 0344 and Figure 17]
Andresen implicitly discloses the composition is capable of forming a homogeneous solution at 20°C. Andresen discloses (1) the composition is injectable and (2) in order for the composition to be injectable, it should be in a sol state with a sufficiently low viscosity at 20°C. [Andresen, 0100, 0329, 0345] A sol state is a homogeneous distribution. Therefore, the composition is necessarily a homogeneous solution at 20°C.
Andresen implicitly discloses that the solvent dissolves the hydrophobic saccharide in the presence of the lipid oil. [Andresen, 0344] As explained above, the composition disclosed by Andresen is a homogeneous solution at 20°C. Accordingly, when the hydrophobic saccharide is combined with the solvent in the presence of the lipid oil, the solvent necessarily dissolves the hydrophobic saccharide to achieve said homogeneity.
Andresen discloses the solvent is capable of diffusing into an aqueous environment, the human or animal body, upon administration to form a depot. [Andresen, 0030, 0195]
With respect to claim 4, Andresen discloses the aforementioned compositions may comprise an iodinated derivative of lactose. [Andresen, 0097]
With respect to claim 6, Andresen discloses the composition comprises a lipid oil, glyceryl trioctanoate. [Andresen, 0344, Figure 17d]
With respect to claim 10, Andresen discloses that about 78% of the composition is a hydrophobic saccharide. [Andresen, 0344, Figure 17d]
With respect to claim 11, Andresen discloses the composition comprises 2% PLGA. [Andresen, 0344 and Figure 17]
With respect to claim 12, Andresen discloses the solvent constitutes 15% of the composition. [Andresen, 0344, Figure 17d]
With respect to claim 16, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is chemically stable for more than 7 days at 20°C.
With respect to claim 17, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is a drug that modulates an immune response.
With respect to claim 18, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is a TLR7 agonist. Andresen further discloses the composition may comprise a combination of two drugs, including resiquimod, imiquimod, R850, R851, TMX-101, TMX-201, TMX-202, which are TLR7 agonists that modulate an immune response. [Andresen, 0119, 0123]
With respect to claim 28, Andresen discloses the API, imiquimod, is dissolved at a concentration of about 2.6 mg/g. [Andresen, 0344] Andresen implicitly discloses the APIs are dissolved at 20°C. As described above, the composition is necessarily a homogeneous solution at 20°C. In a homogeneous mixture, solutes are completely dissolved. Accordingly, the APIs are necessarily dissolved at 20°C to achieve said homogeneity.
With respect to claim 33, Andresen discloses that APIs are released from the composition after administration to a human or animal body at comparable rates. [Andresen, 0114, 0124, 0206, 0230]
With respect to claim 35, Andresen discloses the composition may comprise contrast agents that make the composition visible in X-ray imaging, including one or more iodinated polymers, iodinated oligomers, iodinated lipids, iodinated saccharides, iodinated disaccharides, iodinated polysaccharides, iodinated peptides, or a derivative or a combination thereof. [Andresen, 0097]
With respect to claim 39, Andresen discloses the composition may comprise iodinated saccharides, iodinated disaccharides, iodinated polysaccharides, or a derivative or a combination thereof. [Andresen, 0097]
With respect to claim 44, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Less than 10% of imiquimod changes chemical structure within 7 days at less than 20°С.
With respect to claims 45-46, 50, and 51, Andresen discloses the solvent is EtOH and propylene carbonate. [Andresen, 0344 and Figure 17d]
Moreover, Andresen discloses lactose acetate:propionate (1:1) functions as the gel-forming sugar (saccharide) ester. [Andresen, 0319-0320] Andresen further discloses the gel-forming component may be composed of derivatized saccharides such as esterified saccharides. [Andresen, 0075-0076] Andresen also discloses the gel forming component is a monosaccharide, disaccharide, or trisaccharide scaffold prepared by reacting one or more alcohols, in particular one or more polyols, which will form the alcohol moiety of the resulting esters with one or more carboxylic acids, lactones, lactams, carbonates, or anhydrides of the carboxylic acids which will form the acid moieties of the resulting esters. The esterification reaction can be conducted simply by heating, although in some instances addition of a strong acid or strong base esterification catalyst may be used. [Andresen, 0095] Andresen further discloses the non-water-soluble carbohydrate may be a derivative selected from derivatives of lactose. [Andresen, Abstract and 0012]
Andresen does not disclose that the hydrophobic saccharide is lactose benzoate (LacBen) or α,B-Lactose iodobenzoate or that the composition comprises an iodinated lactose derivative.
However, with respect to claims 1 and 2, Chung discloses that lactose octabenzoate is a lactose derivative. [Chung, 0128]
Modifying the composition disclosed by Andresen by replacing the gel-forming sugar (saccharide) ester, lactose acetate:propionate (1:1), with lactose octabenzoate results in the composition of claim 1, wherein the composition comprises a hydrophobic saccharide, lactose benzoate (LacBen).
With respect to claim 38, Andresen and Chung disclose that the lactose benzoate is lactose octabenzoate.
Further modifying the composition disclosed by Andresen and Chung by iodinating lactose octabenzoate results in the composition of claim 2, wherein the hydrophobic saccharide comprises, lactose iodobenzoate.
It would have been obvious to one of ordinary skill in the art to modify the composition disclosed by Andresen by replacing the gel-forming sugar (saccharide) ester, lactose acetate:propionate (1:1), with lactose octabenzoate and have a reasonable expectation of success. Andresen discloses a composition comprising lactose acetate:propionate (1:1). Andresen discloses lactose acetate:propionate (1:1) is a hydrophobic, esterified saccharide that functions as the gel-forming component of the composition. Andresen further discloses the gel-forming component may include derivatized saccharides (e.g., esterified saccharides), including a derivative of lactose. Andresen additionally discloses the scaffold ester can be made by reacting one or more alcohols which will form the alcohol moiety of the resulting esters with one or more carboxylic acids which will form the acid moieties of the resulting esters. Chung discloses that lactose octabenzoate is a lactose derivative. Accordingly, the combined teachings of Andresen and Chung suggest that the hydrophobic saccharide derivative in the composition disclosed by Andresen may be replaced with another saccharide derivative, lactose octabenzoate. One would have been motivated to do so because Andresen provides an express rationale to modify the composition. MPEP 2144(I). Andresen discloses that the gel-forming component of the composition may be a derivative of lactose. [Andresen, 0075-0076] Therefore, one would have been motivated to replace lactose acetate:propionate (1:1) with lactose octabenzoate because Chung discloses that lactose octabenzoate is a derivative of lactose, and thus may function as the gel-forming component disclosed by Andresen. Moreover, one would have been motivated to do so because it is prima facie obvious to substitute equivalents known for the same purpose when the equivalency is recognized in the prior art. MPEP 2144.06(II). In the present case, Andresen discloses that lactose acetate:propionate (1:1) is a saccharide derivative and Chung that discloses lactose benzoate is a saccharide derivative. Therefore, it is prima facie obvious to substitute one known saccharide derivative (lactose acetate:propionate) for another (lactose benzoate).
It would have been obvious to one of ordinary skill in the art to further modify the composition disclosed by Andresen and Chung by iodinating lactose octabenzoate and have a reasonable expectation of success. Andresen and Chung disclose a composition comprising lactose octabenzoate, which is a derivative of lactose. Andresen further discloses the composition may comprise an iodinated derivative of lactose. Accordingly, the combined teachings of Andresen and Chung reasonably suggest that the derivative of lactose, lactose octabenzoate, present in the composition may be iodinated to yield an iodinated derivative of lactose. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Andresen discloses that including iodinated derivatives of lactose in the composition enables the composition to be used as an X-ray contrast agent. [Andresen, 0097] Therefore, one would have been motivated by the expectation that iodinating the lactose octabenzoate would enable the composition to be used as an X-ray contrast agent.
Claims 1, 2, 3, 4, 6, 10, 11, 12, 13, 14, 16, 17, 18, 28, 33, 35, 39, 44-46, 47, 48, 50, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Andresen and Chung, as applied to claims 1, 2, 4, 6, 10, 11, 12, 16, 17, 18, 28, 33, 35, 38, 39, 44-46, 50, and 51 above, and further in view of Jeong (US 2004/0087567 A1, Published 5/6/2004).
With respect to claim 1, Andresen and Chung disclose the teachings above.
With respect to claim 3, 47, and 48, Andresen and Chung disclose that the composition may comprise iodinated lipids for use as an X-ray contrast agent. [Andresen, 0097]
Andresen and Chung do not disclose that the lipid oil is an ethiodized oil.
However, with respect to claims 3, 47, and 48, Jeong discloses that Lipiodol (ethiodized oil) is an iodinated lipid and contrast medium. [Jeong, 0004] Ethiodized oil is a combination of iodine and ethyl esters of poppy seed oil.
Modifying the compositions disclosed by Andresen and Chung by replacing glycerol trioctanoate with an ethiodized oil results in the composition of claim 3, 47, and 48.
With respect to claim 13, the modified composition comprises LacBen:ethiodized oil:EtOH, wherein imiquimod is dissolved.
With respect to claim 14, the modified composition comprises LacBen:ethiodized oil:EtOH and wherein imiquimod is dissolved. Andresen further discloses the composition may comprise 49-80 % gel-forming carbohydrate (e.g., LacBen), 0-50 % additive (e.g., glycerol trioctanoate or an X-ray contrast agent), and 20-30% non-toxic water-miscible solvent (e.g., EtOH). [Andresen, 0082, 0132, 0135, 0329] Accordingly, modifying the composition disclosed by Andresen, Chung, and Jeong by adjusting the amount of LacBen:ethiodized oil:EtOH to 60:25:15 w/w results in the composition of claim 14.
It would have been obvious to one of ordinary skill in the art to modify the composition disclosed by Andresen and Chung by replacing glycerol trioctanoate with an ethiodized oil and have a reasonable expectation of success. Andresen and Chung disclose a composition comprising a lipid oil, glycerol trioctanoate. Andresen discloses glycerol trioctanoate functions as an additive in the composition. Andresen further discloses the composition may comprise iodinated lipids, which may also function as an additive in the composition and enable the composition to be used as an X-ray contrast agent. Jeong discloses Lipiodol (ethiodized oil) is an iodinated lipid and contrast medium. Accordingly, the combined teachings of Andresen/Chung and Jeong reasonably suggest that ethiodized oil may function as the lipid oil and additive in the composition disclosed by Andresen and Chung. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the instant case, Andresen discloses that including iodinated lipids in the composition enables the composition to be used as an X-ray contrast agent. [Andresen, 0097] Therefore, one would have been motivated by the expectation that the aforementioned modification would enable the composition disclosed by Andresen and Chung to be used as an X-ray contrast agent.
It would be obvious to one of ordinary skill in the art to further modify the composition disclosed by Andresen, Chung, and Jeong by adjusting the weight of LacBen:Ethiodized Oil:EtOH to 60:25:15 w/w and have a reasonable expectation of success through routine optimization.
Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. The general conditions of the instant composition are disclosed by Andresen, Chung, and Jeong, as described above; thus, it is not inventive to discover the optimum or workable ratio of LacBen:Ethiodized Oil:EtOH by routine experimentation. MPEP 2144.05(II)(A).
It would have been routine optimization to arrive at the claimed invention because the weight of the composition is a result-effective variable that influences the kinetics of the compounds released from the compositions. [Andresen, 0113, 0127, 0329] Andresen, Chung, and Jeong disclose a composition comprising LacBen:Ethiodized Oil:EtOH. Andresen further discloses the composition may comprise 49-80 % gel-forming carbohydrate (e.g., LacBen), 0-50 % additive (e.g., X-ray contrast agent), and 20-30% non-toxic water-miscible solvent (e.g., EtOH) relative to the total composition. Andresen discloses that the weight of the composition correlates with the release kinetics of different compounds from the composition. [Andresen, 0113, 0127, 0329] Therefore, it would have been routine optimization to modify the weight of LacBen:Ethiodized Oil:EtOH to optimize the release kinetics of the pharmaceutical released from the composition.
A person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range because the claimed ratio, 60:25:15 (w/w), lies within or is mathematically close to the ranges disclosed by Andresen. MPEP 2144.05(I). Moreover, Andresen discloses several compositions, wherein the solvent constitutes 15 (w/w) of the composition. [Andresen, 0331, 0333, 0334, 0340, 0347, 0349] Therefore, it is prima facie obvious to modify the composition disclosed by Andresen, Chung, and Jeong by adjusting the components within the amounts disclosed by the prior art.
Claims 1, 4, 6, 10-14, 16-18, 28, 33, 35, 39, 44-46, and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Andresen, in view of Jacques (US 3,655,645, Patented 4/11/1972).
With respect to claim 1, Andresen discloses a composition comprising;
A) a hydrophobic saccharide, lactose acetate:propionate (1:1) (78% w/w)
B) a solvent, propylene carbonate (5% w/w) and EtOH (10% w/w)
C) a lipid oil, glycerol trioctanoate (5% w/w); and
D) an active pharmaceutical ingredient (API), imiquimod. [Andresen, 0344 and Figure 17]
Andresen implicitly discloses the composition is capable of forming a homogeneous solution at 20°C. Andresen discloses (1) the composition is injectable and (2) in order for the composition to be injectable, it should be in a sol state with a sufficiently low viscosity at 20°C. [Andresen, 0100, 0329, 0345] A sol state is a homogeneous distribution. Therefore, the composition is necessarily a homogeneous solution at 20°C.
Andresen implicitly discloses that the solvent dissolves the hydrophobic saccharide in the presence of the lipid oil. [Andresen, 0344] As explained above, the composition disclosed by Andresen is a homogeneous solution at 20°C. Accordingly, when the hydrophobic saccharide is combined with the solvent in the presence of the lipid oil, the solvent necessarily dissolves the hydrophobic saccharide to achieve said homogeneity.
Andresen discloses the solvent is capable of diffusing into an aqueous environment, the human or animal body, upon administration to form a depot. [Andresen, 0030, 0195]
With respect to claim 4, Andresen discloses the composition may comprise an iodinated derivative of lactose. [Andresen, 0097]
With respect to claim 6, Andresen discloses the composition comprises a lipid oil, glyceryl trioctanoate. [Andresen, 0344, Figure 17d]
With respect to claim 10, Andresen discloses that about 78% of the composition is a hydrophobic saccharide. [Andresen, 0344, Figure 17d]
With respect to claim 11, Andresen discloses the composition comprises 2% PLGA. [Andresen, 0344, Figure 17d]
With respect to claim 12, Andresen discloses the solvent constitutes 15% of the composition. [Andresen, 0344, Figure 17d]
With respect to claim 16, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is chemically stable for more than 7 days at 20°C.
With respect to claim 17, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is a drug that modulates an immune response.
With respect to claim 18, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Imiquimod is a TLR7 agonist. Andresen further discloses the composition may comprise a combination of two drugs, including resiquimod, imiquimod, R850, R851, TMX-101, TMX-201, TMX-202, which are TLR7 agonists that modulate an immune response. [Andresen, 0119, 0123]
With respect to claim 28, Andresen discloses the API, imiquimod, is dissolved at a concentration of about 2.6 mg/g. [Andresen, 0344] Andresen implicitly discloses the APIs are dissolved at 20°C. As described above, the composition is necessarily a homogeneous solution at 20°C. In a homogeneous mixture, solutes are completely dissolved. Accordingly, the APIs are necessarily dissolved at 20°C to achieve said homogeneity.
With respect to claim 33, Andresen discloses that APIs are released from the composition after administration to a human or animal body at comparable rates. [Andresen, 0114, 0124, 0206, 0230]
With respect to claim 35, Andresen discloses the composition may comprise contrast agents that make the composition visible in X-ray imaging, including one or more iodinated polymers, iodinated oligomers, iodinated lipids, iodinated saccharides, iodinated disaccharides, iodinated polysaccharides, iodinated peptides, or a derivative or a combination thereof. [Andresen, 0097]
With respect to claim 39, Andresen discloses the composition may comprise iodinated saccharides, iodinated disaccharides, iodinated polysaccharides, or a derivative or a combination thereof. [Andresen, 0097]
With respect to claim 44, Andresen discloses the API is imiquimod. [Andresen, 0344, Figure 17d] Less than 10% of imiquimod changes chemical structure within 7 days at less than 20°С.
With respect to claims 45-46, 50, and 51, Andresen discloses the solvent is EtOH and propylene carbonate. [Andresen, 0344 and Figure 17d]
Moreover, Andresen discloses lactose acetate:propionate (1:1) functions as the gel-forming sugar (saccharide) ester. [Andresen, 0319-0320] Andresen further discloses the gel-forming component may be composed of derivatized saccharides such as esterified saccharides. [Andresen, 0075-0076] Andresen also discloses the gel forming component is a monosaccharide, disaccharide, or trisaccharide scaffold prepared by reacting one or more alcohols, in particular one or more polyols, which will form the alcohol moiety of the resulting esters with one or more carboxylic acids, lactones, lactams, carbonates, or anhydrides of the carboxylic acids which will form the acid moieties of the resulting esters. The esterification reaction can be conducted simply by heating, although in some instances addition of a strong acid or strong base esterification catalyst may be used. Andresen discloses the scaffold is preferably sucrose or lactose. [Andresen, 0095]
Andresen does not disclose that the hydrophobic saccharide is sucrose benzoate (SuBen).
However, with respect to claim 1 and 49, Jacques discloses that saccharose benzoate (also known as sucrose benzoate) is a saccharide derivative and that acetate and benzoate are both saccharide esters. [Jacques, Col. 2, Line 7-11]
Modifying the composition disclosed by Andresen by replacing the gel-forming sugar (saccharide) ester, lactose acetate:propionate (1:1), with sucrose benzoate results in the composition of claim 1 and 49, wherein the composition comprises a hydrophobic saccharide, sucrose benzoate (SuBen).
With respect to claim 13, the modified composition comprises SuBen:GTO:EtOH and wherein imiquimod is dissolved. [Andresen, 0344]
With respect to claim 14, the modified composition comprises SuBen:GTO:EtOH and wherein imiquimod is dissolved. [Andresen, 0344] Andresen further discloses the composition may comprise 49-80 % gel-forming carbohydrate (e.g., SuBen), 0-50 % additive (e.g., glycerol trioctanoate), and 20-30% non-toxic water miscible solvent (e.g., EtOH). [Andresen, 0082, 0329] Accordingly, modifying the composition disclosed by Andresen and Jacques by adjusting the weight of SuBen:GTO:EtOH to 60:25:15 w/w results in the composition of claim 14.
It would have been obvious to one of ordinary skill in the art to modify the composition disclosed by Andresen by replacing the gel-forming sugar (saccharide) ester, lactose acetate:propionate (1:1), with sucrose benzoate and have a reasonable expectation of success. Andresen discloses a composition comprising a sugar (saccharide) ester, lactose acetate:propionate (1:1). Andresen discloses lactose acetate:propionate (1:1) is a hydrophobic, esterified saccharide that functions as the gel-forming component of the composition. Andresen further discloses the gel-forming component may include derivatized saccharides (e.g., esterified saccharides). Andresen identifies sucrose as a preferred scaffold for the gel-forming component. Andresen additionally discloses that the scaffold ester can be made by reacting one or more alcohols which will form the alcohol moiety of the resulting esters with one or more carboxylic acids which will form the acid moieties of the resulting esters. Jacques discloses that sucrose benzoate is a saccharide derivative and that acetate and benzoate are both saccharide esters. Accordingly, Jacques establishes that benzoate and acyl groups such as acetate are interchangeably used to esterify saccharides, specifically sucrose, to form saccharide derivatives. Therefore, the combined teachings of Andresen and Jacques reasonably suggest that the gel-forming component of the composition may be another saccharide derivative, sucrose benzoate. One would have been motivated to do so because it is prima facie obvious to substitute equivalents known for the same purpose when the equivalency is recognized in the prior art. MPEP 2144.06(II). In the present case, Andresen discloses lactose acetate:propionate (1:1) is a saccharide derivative, and Jacques discloses sucrose benzoate is a saccharide derivative. Therefore, it is prima facie obvious to substitute one known saccharide derivative (lactose acetate:propionate) for another (sucrose benzoate).
It would have been obvious to one of ordinary skill in the art to further modify the composition disclosed by Andresen and Jacques by adjusting the weight of SuBen:GTO:EtOH to 60:25:15 w/w and have a reasonable expectation of success through routine optimization.
Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. The general conditions of the instant composition are disclosed by Andresen and Jacques, as described above; thus, it is not inventive to discover the optimum or workable ratio of SuBen:GTO:EtOH by routine experimentation. MPEP 2144.05(II)(A).
It would have been routine optimization to arrive at the claimed invention because the weight of the composition is a result-effective variable that influences the kinetics of the compounds released from the compositions. [Andresen, 0113, 0127, 0329] Andresen and Jacques disclose a composition comprising SuBen:GTO:EtOH. Andresen further discloses the composition may comprise 49-80 % gel-forming carbohydrate (e.g., SuBen), 0-50 % additive (e.g., glycerol trioctanoate), and 20-30% non-toxic water-miscible solvent (e.g., EtOH) relative to the total composition. Andresen discloses that the weight of the composition correlates with the release kinetics of different compounds from the composition. [Andresen, 0113, 0127, 0329] Therefore, it would have been routine optimization to modify the weight of SuBen:GTO:EtOH to optimize the release kinetics of the pharmaceutical released from the composition.
A person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range because the claimed ratio, 60:25:15 (w/w), lies within or is mathematically close to the ranges disclosed by Andresen. MPEP 2144.05(I). Moreover, Andresen discloses several compositions, wherein the solvent constitutes 15 (w/w) of the composition. [Andresen, 0331, 0333, 0334, 0340, 0347, 0349] Therefore, it is prima facie obvious to modify the composition disclosed by Andresen and Jacques by adjusting the components within the weights disclosed by the prior art.
Response to Arguments
Applicant’s arguments with respect to claims 1, 2, 4, 6, 10-12, 16-18, 28, 35, 38, 39 and 44-46 over Andresen and Albrechtsen have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. [Remarks 4/6/2026, Page 13 – Page 17, Paragraph 2]
Applicant's arguments filed 4/6/2026 over Andresen + Chung and Andresen + Chung + Jeong have been fully considered but they are not persuasive.
Applicant asserts the following:
“To arrive at the present claims from the cited prior art, the Examiner's path would
require hindsight in which beginning with the Andresen four-component framework, the
artisan would be required to ignore the aliphatic core teaching, and in the complete
absence of any motivation or suggestion, import from Chung, a wholly different, cationic
transporter concept, and somehow land on the aromatic benzoate set recited in claim 1,
without any motivation or suggestion to do so.” [Remarks 4/6/2026, Page 17, Paragraph 5]
“There is no motivation or suggestion to selection the Applicant's recited limitations
from the broad genus of Andresen umbrella of "non-water-soluble carbohydrate
derivatives", which is vast, and which fails to disclose or suggest benzoate saccharides.” [Remarks 4/6/2026, Page 18, Paragraph 3]
Applicant mischaracterizes Andresen by improperly limiting the disclosure to an “aliphatic core teaching.” The basis for combining the teachings of Andresen with Chung relies on Andresen’s teaching that lactose acetate:propionate (1:1) functions as the gel-forming sugar (saccharide) ester. [Andresen, 0319-0320] Andresen further discloses the gel-forming component may be composed of derivatized saccharides such as esterified saccharides. [Andresen, 0075-0076] Notably, Andresen does not assert the gel-forming component may be composed of derivatized saccharides with an aliphatic core. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. MPEP 2123(I). Andresen may exemplify compositions comprising aliphatic saccharides, but Andresen evidently does not limit the gel-forming component to this embodiment.
Moreover, Andresen provides a motivation and suggestion to modify the composition disclosed by Andresen by replacing the gel-forming sugar (saccharide) ester, lactose acetate:propionate (1:1), with sucrose benzoate for the reasons provided above. Briefly, Andresen discloses a composition comprising lactose acetate:propionate (1:1). Andresen discloses that lactose acetate:propionate (1:1) is a hydrophobic, esterified saccharide that functions as the gel-forming component of the composition. Andresen further discloses the gel-forming component may include derivatized saccharides (e.g., esterified saccharides), including a derivative of lactose. Therefore, Andresen affirmatively suggests that the gel-forming component of the composition may be a lactose derivative. Accordingly, Chung discloses that lactose octabenzoate is a lactose derivative. Notably, the rejection of record does not rely on Chung’s teachings regarding the cationic transporter concept. Rather, the rejection of record relies on Chung’s identification of lactose octabenzoate as a lactose derivative. Accordingly, the combined teachings of Andresen and Chung suggest that the hydrophobic saccharide derivative in the composition disclosed by Andresen may be replaced with another saccharide derivative, lactose octabenzoate.
However, even if, arguendo, Andresen did not provide a reason to modify the composition, this argument would still be insufficient to establish that the claimed invention is non-obvious. The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art, or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. MPEP 2144(I).
Applicant asserts “Benzoate/iodobenzoate saccharide are absent in both Andresen and Chung, wherein Andresen discloses aliphatic acyls/SAIB and Chung discloses guanidinium-rich transporters, not benzoates…. In addition, the while Andresen is homogeneous at 20 °C for pre-injection liquids, Andresen fails to disclose benzoates as recited in the present claims. Chung makes no such disclosure.” [Remarks 4/6/2026, Page 17, Paragraph 5 – Page 18, Paragraph 1]
Benzoates are not absent from Chung. Octa-O-benzoyl-α-lactose (disclosed by Chung) is a benzoate.
Applicant asserts “Andresen discloses aliphatic acyls/SAIB…” [Remarks 4/6/2026, Page 17, Paragraph 5 – Page 18, Paragraph 1]
Applicant mischaracterizes Andresen by improperly limiting the disclosure to an “aliphatic acyls/SAIB.” The basis for combining the teachings of Andresen with Chung relies on Andresen’s teaching that lactose acetate:propionate (1:1) functions as the gel-forming sugar (saccharide) ester. [Andresen, 0319-0320] Andresen further discloses the gel-forming component may be composed of derivatized saccharides such as esterified saccharides. [Andresen, 0075-0076] Notably, Andresen does not assert the gel-forming component may be composed of derivatized saccharides with aliphatic acyls or SAIB. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. MPEP 2123(I). Andresen may exemplify compositions comprising aliphatic acyls and SAIB, but Andresen evidently does not limit the gel-forming component to this embodiment.
Applicant asserts “The lipid oil of Andresen is GTO/GTH; vegetable oils, while Chung fails to disclose or suggest any.” [Remarks 4/6/2026, Page 17, Paragraph 5 – Page 18, Paragraph 1]
Chung discloses that lactose octabenzoate is a lactose derivative. Notably, the rejection of record does not rely on Chung’s teachings regarding lipid oils. Rather, the rejection of record relies on Chung’s identification of lactose octabenzoate as a lactose derivative.
Applicant asserts “The API disclosed by Andresen is a broad list, while Chung discloses cargo but not depot formulations.” [Remarks 4/6/2026, Page 17, Paragraph 5 – Page 18, Paragraph 1]
The API disclosed by Andresen is not a broad list. The rejection relies on the composition described in [0344], which is drawn to only one API – imiquimod.
Chung discloses that lactose octabenzoate is a lactose derivative. Notably, the rejection of record does not rely on Chung’s teachings regarding depot formulations. Rather, the rejection of record relies on Chung’s identification of lactose octabenzoate as a lactose derivative.
Applicant asserts “Jeong is directed to radiolabelled chelators in Lipiodol for hepatic arterial therapy. Jeong is non-analogous to the present claims. Jeong fails to disclose or suggest saccharide-based depot excipients nor room-temperature homogeneity of four-component drug systems. As such, it is remote from the claimed selection problem and provides no motivation to adopt benzoate saccharides. In addition, the cited prior art fails to provide any interplay at 20 °C. The claim's requirement that the benzoate saccharide + solvent + lipid oil + API mixture be homogeneous at 20 °C is not addressed in Jeong and is not predictable from Andresen's aliphatic landscape.” [Remarks 4/6/2026, Page 18, Paragraph 4-5]
The instant claims are drawn to a composition comprising a lipid oil and iodinated agents. Jeong discloses that Lipiodol (ethiodized oil) is an iodinated lipid and contrast medium. Notably, the rejection of record does not rely on Jeong’s teachings regarding saccharide-based depot excipients nor room-temperature homogeneity of four-component drug systems, a motivation to adopt benzoate saccharides, or that the benzoate saccharide + solvent + lipid oil + API mixture be homogeneous at 20 °C. Rather, the rejection of record relies on Jeong’s identification of ethiodized oil as an iodinated lipid and an iodinated medium. Accordingly, since ethiodized oil is both a lipid oil and an X-ray contrast agent, the teachings of Jeong are reasonably pertinent to the claimed invention.
The "reasonably pertinent" test considers the problem faced by the inventor, as reflected either explicitly or implicitly in the specification. The specification contemplates the inclusion of an iodinated lipid oil for use in the composition. Jeong identifies ethiodized oil as an iodinated lipid oil. Hence why an inventor seeking to select an iodinated lipid oil for use in the composition would have looked to Jeong to find a solution to the problem.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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