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 .
Priority
The present application, filed August 16, 2023, is a national stage application of PCT/EP2022/053948, filed February 17, 2022, which claims priority to foreign priority application LU102545, filed February 17, 2021, and EP21157724.2, filed February 17, 2021.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on February 19, 2026 is acknowledged.
Claims 6-7 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 February 19, 2026.
Status of the Application
Applicant’s communication, received February 19, 2026, wherein claims 6-7 and 13 are canceled, is acknowledged.
Claims 1-5, 8-12, and 14-15 are pending and examined on the merits herein.
Claim Objections
Claims 1-5, 8, and 12 are objected to because of the following informalities:
Claim 4 recites the structure shown in ii), and claim 5 recites the structure shown in iv). Although these structures are larger than the structures they replace, they are still of low resolution. Please replace these structures with higher resolution structures.
Claim 1 recites: “i) at least one polysaccharide (Pl) selected from the group consisting of starch, amylase, amylopectin, cellulose, glycogen, chitosan, methylmannose and…”. Please amend this limitation to recite: “i) at least one polysaccharide (Pl) selected from the group consisting of starch, amylase, amylopectin, cellulose, glycogen, chitosan, and methylmannose, and…”.
Claim 1 recites: “(C6-C80)alkane or (C6-C80)alkenyl” when defining R1 in (ii). To be consistent with definition of R1, please amend this limitation to recite: “(C6-C80)alkyl or (C6-C80)alkenyl.”
Claim 1 recites: “n, o, p, q, and r are independently selected from is an integer ranging from 4-17.” Please amend to recite: “n, o, p, q, and r are independently selected from s ranging from 4-17.”
Claim 4 recites the R3 group of i). However, this R3 group is missing several dashes. Please correct the name of this R3 group.
Claim 5 recites a Markush group of gangliosides in section vi). Please amend the last line of this section to read as “3’SLN, and 6’SL.”
Claim 8 recites: “i) in the ratio between the most frequent binding type in the polysaccharide (Pl) between the monosaccharides and the less frequent binding type between monosaccharides is at least 15:1.” Please amend to recite: “i) the ratio between the most frequent binding type in the polysaccharide (P1) between the monosaccharides and the less frequent binding type between monosaccharides is at least 15:1.”
Claim 12 recites: “wherein said composition is suitable for oral, enteral, dermal, topical, urogenital, inhalational administration.” Please amend claim 12 to recite: “wherein said composition is suitable for oral, enteral, dermal, topical, urogenital, or inhalational administration.”
Finally, the claims received February 19, 2026 are not properly annotated. For example, claim 1 is not indicated as amended, but this claim 1 is not the same claim 1 in the claims received August 16, 2023.
Claim 2 received February 19, 2026 has limitation I) removed from the claim, but this amendment is not annotated.
Claim 3 received February 19, 2026 is different claim that received August 16, 2023, but these changes are not annotated.
For all future amendments, please properly annotate the claims to show how the claims have been amended.
Appropriate correction is required.
Claim Interpretation
The present claims require a polysaccharide complex. In the absence of an express definition provided in the specification, the term complex is interpreted consistent with its customary meaning in the art. Britannica (Brittanica entry for "complex" cited in PTO-892) teaches that a complex, in chemistry, is a substance, formed by the union of simpler substances (as compounds or ions) and held together by forces that are chemical.
Therefore, any chemical interaction of two compounds in a composition is interpreted herein as a complex.
Claim 9 recites: “A polysaccharide complex prepared by a method comprising the step of combining the polysaccharide (P1) and a heterologous lipid carrier as defined in claim 1 in a solution. Claim 9 is interpreted herein as a product-by-process that is satisfied by a product that satisfies the requirements of the product of claim 1, even if that product were produced by another method.
MPEP 2113 at I states: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Accordingly, claim 9 is considered satisfied by a polysaccharide complex that satisfies claim 1, even if that polysaccharide complex were produced by a different method.
Claim 11 recites: “The polysaccharide complex of claim 1, A) for use in medicine or B) for use in the treatment of a subject comprising i) binding and/or reducing toxicity of and/or neutralizing a toxin; ii) binding and/or reducing the pathogenicity and/or neutralizing a pathogenic microorganism; iii) binding a receptor of a toxin; iv) binding a receptor of a pathogenic microorganism; v) eliciting or modulating an immune response; vi) preventing disease; vii) monitoring the development of a disease and/or assessing the efficacy of a therapy of a disease; viii) delivering a pharmaceutically active compound, preferably said delivering is to a mucosal tissue of a subject; or C) in an in vivo or in vitro method of diagnosis.
The limitations A), B), and C) in claim 11 are interpreted herein as intended uses of the polysaccharide complex of claim 1.
MPEP 2111.02 (II) states: “During examination, statements in the preamble reciting
the purpose or intended use of the claimed invention must be evaluated to determine whether or
not the recited purpose or intended use results in a structural difference (or, in the case of process
claims, manipulative difference) between the claimed invention and the prior art. If so, the
recitation serves to limit the claim. …To satisfy an intended use limitation which is limiting, a
prior art structure which is capable of performing the intended use as recited in the preamble
meets the claim.”
In this instance, because the intended use does not limit the structure of the polysaccharide complex recited in claim 11, claim 11 is considered satisfied by a polysaccharide complex of claim 1, even if that polysaccharide complex is not used for the intended uses of A), B), or C).
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 8-12, and 14-15 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites: “the peptide comprises 2 to 100 amino acids.” However, claim 1 permits R3 as at least one peptide moiety or a polysaccharide peptide moiety comprising an a-linked or a β-linked mono-, di- or polysaccharide and at least one peptide. Therefore, it is unclear if the peptide comprising 2 to 100 amino acids refers to the at least one peptide moiety, the at least one peptide that is part of the polysaccharide peptide moiety, or both.
Because claims 2-3, 8-12, and 14-15 depend from claim 1 and fail to cure this deficiency, claims 2-3, 8-12, and 14-15 are also indefinite.
Regarding claim 1, the phrases "preferably", "more preferably", and "most preferably" when defining group R1 render the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Because claims 2-4, 8-12, and 14-15 depend from claim 1 and fail to cure this deficiency, claims 2-4, 8-12, and 14-15 are also indefinite.
Regarding claim 3, the phrases "more preferably" recited when defining the peptide and when defining variable group R3 render the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8, the phrases "preferably" and "more preferably" in i) and the phrase "preferably" in ii) render the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11, the phrase "preferably" in viii) renders the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 2 recites: “the polysaccharide complex, in particular the bonding between i) and ii) is stable against at least one of the following conditions:”.
The phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For example, it is unclear if claim 2 would be satisfied if the bonding between i) and ii) were stable but the polysaccharide complex were to degrade in some other way not affecting binding between i) and ii).
Claim 3 recites: The polysaccharide complex of claim 1 wherein the polysaccharide (P2) comprises 2 to 30 monosaccharide moieties; the peptide comprises 2 to 30, most preferably 2 to 20 amino acids; R3 is selected from the group consisting of a polysaccharide, the heterologous lipid carrier may be further modified with at least one further group A as listed in the claim.
This claim lacks conjunctions between limitations, and thus it is unclear if each of this limitations are required, or if only one of these limitations is required. Moreover, if all limitations are required, then R3 must be a polysaccharide, as recited in the claim. Accordingly, the limitations relating to the peptide would not be relevant to claim 3, because claim 3 does not permit the peptide or the polysaccharide peptide moiety recited in claim 1 as variable group R3.
Claim 5 recites, for limitation (iv): “a GM1-Gb3 chimera having the formula (III).” However, the structure labeled as (III) shown in the claim is also labeled as formula (I). Moreover, formula (I) is already recited in claim 1 to define a different structure. Accordingly, the structure of formula (III) as recited in (iv) in claim 5 is unclear. In addition, because (iv) of claim 5 recites a compound of formula (I) different than the formula (I) of claim 1, claim 5 recites a limitation that conflicts with claim 1. Finally, (iv) of claim 5 recites that R3 is the non-lipid part of formula (III). However, if formula (III) is the structure shown in (iv) of claim 5, it is unclear what the limitation non-lipid part refers to, because the structure of formula (III) does not include a lipid part.
Claim 14 recites the limitation "composition according to claim 1" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 14 depends from claim 1, but claim 1 does not recite a composition.
Because claim 15 depends from claim 14 and fails to cure this deficiency, claim 15 is also indefinite.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claims 9 and 11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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.
Claim 9 recites: “A polysaccharide complex prepared by a method comprising the step of combining the polysaccharide (P1) and a heterologous lipid carrier as defined in claim 1 in a solution.” As described in the above claim interpretation section, claim 9 is interpreted herein as a product-by-process, wherein determination of patentability is based on the product itself. In this instance, it is unclear how requiring polysaccharide (P1) and a heterologous lipid carrier are combined in solution would limit the structure of the polysaccharide complex of claim 1. Accordingly, claim 9 fails to further limit the subject matter of the claim upon which it depends.
Claim 11 recites: The polysaccharide complex of claim 1, with intended uses A), B), and C) recited in the claim. As described in the above claim interpretation section, the intended uses A), B), and C) do not limit the structure of the polysaccharide complex of claim 1. For example, claiming that the polysaccharide complex is for use in medicine, as recited in claim 11, is an extremely broad limitation and could potentially include any structure recited in claim 1. Therefore, it is unclear how the intended uses of claim 11 limit the structure of the polysaccharide complex of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 3, 4, and 8-12 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Schneider (U.S. pre-grant publication no. 20120220544 A1; cited in PTO-892), as evidenced by Zhao (Zhao, G. H.; et al. International Journal of Pharmaceutics 2011, vol. 415, pp. 95-101; cited in PTO-892).
Schneider teaches and claims a pharmaceutical composition for treatment or prevention of a central nervous system (CNS) disease or condition in a human patient amenable to treatment by therapeutic administration of GM1, comprising a formulation for transmucosal administration comprising: GM1 and at least one permeation-enhancing agent effective to enhance transmucosal drug uptake; at least one buffer; at least one solvent; and at least one osmolarity agent (p. 5, claim 1). Schneider further claims the viscosity agent is selected from a group that includes microcrystalline cellulose (p. 5, claim 12). Schneider teaches GM1 is a monosialoganglioside known to known to modulate a number of cell surface and receptor activities as well as play important roles in neuronal differentiation and development (p. 1, [0008], lines 1-4).
Schneider teaches an example that includes GM-1 and Avicel RC-591. As evidenced by Zhao, Avicel RC 591 is a processed mixture of microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (Na-CMC) and is commonly used as a suspending agent for aqueous compositions (p. 95, Abstract, second paragraph, lines 1-2).
As evidenced by the instant specification, GM1 is a monosialotetrahexosylganglioside that satisfies all limitations of the heterologous lipid carrier of claims 1 and 3 (for example, see the description of GM1 on p. 20, [0062]), and has R3 as the structure of i) recited in claim 4.
Moreover, Schneider teaches that their composition may be an aqueous liquid or gel
solution and formulated for transmucosal administration either buccally, orally, or intranasally (p. 2, [0018], lines 10-13). In this instance, an aqueous solution would require water, which is a pharmaceutically acceptable carrier.
Regarding the requirement that i) and ii) are associated by direct bonding to each other, because each of GM-1 and microcrystalline cellulose are present together, such as in an aqueous solution, they would be expected to interact with each via non-covalent bonding, absent evidence to the contrary.
Regarding the requirements that i) and ii) do not restrict or influence each other’s movement by forming a membrane, and that at least part of i) and ii) is exposed and accessible to the environment, Schneider does not teach the formation of a membrane or other structure formed from GM-1 and Avicel RC 591. Therefore, GM-1 and microcrystalline cellulose would be expected to be exposed and accessible to the environment, absent evidence to the contrary.
Regarding claim 8, because polysaccharide P1 is cellulose, which includes only β-1,4-linked monosaccharides. Accordingly, claim 8 is also anticipated by Schneider.
Thus Schneider anticipates claims 1, 3, 4, and 8-12.
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.
Claims 1, 3, 4, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider (U.S. pre-grant publication no. 20120220544 A1; cited in PTO-892) in view of Yagi-Utsumi (Yagi-Utsumi, M.; et al. Glycoconjugate Journal 2015, vol. 32, pp. 102-112; cited in PTO-892) and Zhao (Zhao, G. H.; et al. International Journal of Pharmaceutics 2011, vol. 415, pp. 95-101; cited in PTO-892).
Claims 1, 3, 4, and 8-12 are anticipated by Schneider, as described in the above rejection under 35 U.S.C. § 102. However, for the sake of argument, if ganglioside GM1 taught by Schneider is not necessarily the same GM1 referred to in the instant specification, then claims 1, 3, 4, and 8-12 would have been obvious over Schneider in view of Yagi-Utsumi and Zhao.
Schneider teaches as described in the above rejection under 35 U.S.C. § 102.
Schneider does not teach the structure of ganglioside GM1 or Avicel RC-591 as a material that includes microcrystalline cellulose.
Yagi-Utsumi teaches the structure of the ganglioside GM1 (p. 107, Figure 1; structure shown below). Ganglioside GM1 taught by Yagi-Utsumi satisfies all limitations of claim 1, wherein the heterologous lipid carrier has the structure of formula (I) with R1 as linear C17 alkyl, R2 as -CH=CH(CH2)rCH3 with r as 12, and R3 as a β-linked polysaccharide moiety. This polysaccharide includes 5 monosaccharides, and thus satisfies the requirements of claim 3. This polysaccharide also includes the specific R-3 group recited in i) in claim 4.
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Zhao teaches Avicel RC 591 is a processed mixture of microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (Na-CMC) and is commonly used as a suspending agent for aqueous compositions (p. 95, Abstract, second paragraph, lines 1-2).
It would have been prima facie obvious to one of ordinary skill in the art to prepare the pharmaceutical composition of Schneider using a GM1 taught by Yagi-Utsumi. One of ordinary skill in the art would have been motivated to prepare the pharmaceutical composition of Schneider using a GM1 taught by Yagi-Utsumi because Schneider teaches their composition as including ganglioside GM1, and because Yagi-Utsumi teaches the structure of ganglioside GM1 as shown above. Accordingly, one of ordinary skill in the art would have considered selecting the GM1 known in the prior art, with the structure as taught by Yagi-Utsumi, for preparing the composition taught by Schneider. This structure of GM1 satisfies the limitations of the heterologous lipid carrier of present claims 1, 3, and 4.
Moreover, one of ordinary skill in the art would have contemplated the composition of Schneider as including microcrystalline cellulose because Schneider teaches a composition comprising Avicel RC-591, and in view of Zhao, one of ordinary skill in then art would have recognized that Avicel RC-591 comprises microcrystalline cellulose.
Regarding the requirement that i) and ii) are associated by direct bonding to each other, because each of GM-1 and microcrystalline cellulose are present in solution together, they would be expected to interact with each via non-covalent bonding, absent evidence to the contrary.
Regarding the requirements that i) and ii) do not restrict or influence each other’s movement by forming a membrane, and that at least part of i) and ii) is exposed and accessible to the environment, Schneider does not teach the formation of a membrane or other structure with GM1 and microcrystalline cellulose. Therefore, GM-1 and microcrystalline cellulose would be expected to be exposed and accessible to the environment, absent evidence to the contrary.
Regarding claim 8, because polysaccharide P1 is cellulose, which includes only β-1,4-linked monosaccharides, claim 8 is also obvious over Schneider in view of Yagi-Utsumi and Zhao.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1 and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lencer (Publication no. WO 2019084456 A1; cited in PTO-892).
Lencer teaches and claims a delivery vehicle comprising a glycosphingolipid and an agent to be delivered, wherein the glycosphingolipid comprises an oligosaccharide, and (a) a ceramide that comprises a short-chain fatty acid (Cl-C3), or (b) a ceramide that does not contain a fatty acid, and wherein the agent to be delivered is attached to the oligosaccharide of the glycosphingolipid (p. 48, claim 1).
Lencer further teaches and claims wherein the glycosphingolipid is a ganglioside (p. 48, claim 2), wherein the ganglioside comprises a sialic acid (p. 48, claim 3), and wherein the ganglioside is monosialotetrahexosylganglioside (GM1) or wherein the ganglioside is monosialodihexosylganglioside (GM3) (p. 48, claims 4 and 5).
Lencer claims the agent to be delivered is a protein or a peptide (p. 49, claim 18), and wherein the protein or peptide is GLP-1 (p. 49, claim 22). Lencer teaches "Glucagon-like peptide-1 (GLP-1)" is a 30 amino acid long peptide hormone (p. 16, last paragraph, lines 1-2).
Lencer claims a composition comprising the delivery vehicle of any one of claims 1-23 and a pharmaceutically acceptable carrier (p. 52, claim 47). Moreover, Lencer teaches that pharmaceutically-acceptable carriers include starches, such as corn starch and potato starch, and cellulose, and its derivatives, such as microcrystalline cellulose (p. 24, lines 17-21).
Lencer teaches the delivery vehicle, the glycosphingolipid-agent complex, or the pharmaceutical composition comprising the delivery vehicle or the glycosphingolipid-agent complex (e.g., the glycosphingolipid-therapeutic agent complex) may be administered by any route, including enteral routes, such as oral routes (p. 27, first full paragraph, lines 1-4).
Finally, Lencer teaches the structure of a specific glycosphingolipid-agent conjugate (document p. 56, Figure 1A). This conjugate has the structure of the heterologous lipid carrier of formula (I) as shown, with R1 as linear C2, C4, C6, C12, or C16 alkyl, R2 as -CH=CH(CH2)rCH3 with r as 12, and with R3 as a polysaccharide with 4 or 5 monosaccharide units conjugated with a 12 amino acid peptide. In this structure, the polysaccharide is either GM1 or GM3. This structure satisfies all limitations of the heterologous lipid carrier of claim 1.
Lencer does not teach a polysaccharide complex comprising the conjugate of Figure 1A with at least one polysaccharide recited in claim 1.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to formulate the delivery vehicle taught by Lencer with the pharmaceutically acceptable carrier starch or cellulose. One of ordinary skill in the art would have been motivated to formulate the delivery vehicle taught by Lencer with the pharmaceutically acceptable carrier starch or cellulose because Lencer teaches the delivery vehicle described above, further teaches and claims the delivery vehicle formulated with a pharmaceutically acceptable carrier, and teaches starch and cellulose as suitable pharmaceutically acceptable carriers. Accordingly, one of ordinary skill in the art would have contemplated the delivery vehicle of Lencer formulated with starch or cellulose.
Regarding the requirement that i) and ii) are associated by direct bonding to each other, because each of the delivery vehicle of Lencer and the carriers starch or cellulose would be formulated together, they would be expected to interact with each via non-covalent bonding, absent evidence to the contrary.
Regarding the requirements that i) and ii) do not restrict or influence each other’s movement by forming a membrane, and that at least part of i) and ii) is exposed and accessible to the environment, Lencer does not teach the formation of a membrane or other structure when the delivery vehicle is formulated with one of their suggested carriers. Therefore, the delivery vehicle and starch or cellulose would be expected to be exposed and accessible to the environment, absent evidence to the contrary.
Regarding claim 8, because polysaccharide P1 is cellulose, which includes only β-1,4-linked monosaccharides, claim 8 is also obvious over Lencer.
As stated, the Office maintains that the structure taught by Lencer would satisfy the requirements of R3 of the heterologous lipid carrier of claim 1. However, if this structure were to not satisfy the requirements of claim 3 because, for example, the peptide is further derivatized with biotin and a fluorophore, then the heterologous lipid carrier would have been obvious over Lencer, as described below.
It would have been obvious to substitute the derivatized peptide structure in the delivery vehicle exemplified by Lencer with the GLP-1 peptide. One of ordinary skill in the art would have been motivated to substitute the derivatized peptide structure in the delivery vehicle taught by Lencer with the GLP-1 peptide because Lencer teaches and claims the therapeutic agent may be a protein or peptide, and further claims the peptide is GLP-1. Accordingly, one of ordinary skill in the art would have contemplated substituting the derivatized peptide in the structure taught by Lencer with GLP-1. Regarding the size of GLP-1, Lencer teaches GLP-1 as 30 amino acids long, and thus the conjugate with GLP-1 would satisfy the requirements of the peptide in the heterologous lipid carrier of claim 1. Furthermore, it would have been obvious to formulate said conjugate comprising GM1 or GM3 taught by Lencer and conjugated with GLP-1 with the pharmaceutically acceptable carrier starch or cellulose, for the same reasons as described above.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1, 3-5, 8-12, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Livingston (Livingston, P. O.; et al. Journal of Clinical Oncology 1994, vol. 12, pp. 1036-1044; cited in PTO-892) in view of Sillerud (Sillerud, L. O; et al. Biochemistry 1982, vol. 21, pp. 1260-1271; cited in PTO-892) and Li (Li, X.; et al. Journal of Immunology Research 2013, article ID 387023; cited in PTO-892).
Livingston teaches a clinical trial in which patients with melanoma were administered a GM2/BCG vaccine or were treated with bacille Calmette-Guerin (BCG) alone (p. 1036, Abstract, Patients and Methods section, lines 1-5). Livingston teaches that GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. Livingston teaches after a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval and a 17% increase in overall survival in these 57 antibody-positive patients (p. 1036, Abstract, Results section, lines 1-7).
Livingston teaches that the vaccine was prepared by suspending Tice-strain BCG was in distilled water by sonication, together with 200 pg of dried purified GM2. Livingston teaches the suspension was lyophilized and stored at -80 °C, and the residue was resuspended in 0.5 mL of phosphate-buffered saline (PBS) shortly before vaccine administration (p. 1037, left column, GM2/BCG vaccine section, second paragraph, lines 1-8). Livingston teaches that patients received the vaccine by intradermal injections (p. 1037, right column, line 10).
Livingston does not teach the carbohydrate complex comprising at least one polysaccharide P1, as required by claim 1. In addition, Livingston does not teach a specific structure of GM2.
Sillerud teaches the structure of ganglioside GM2 (p. 1261, Figure 1). GM2 taught by Sillerud satisfies all limitations of claim 1, wherein the heterologous lipid carrier has the structure of formula (I) with R1 as linear C19 alkyl, R2 as -CH=CH(CH2)rCH3 with r as 14, and R3 as a β-linked polysaccharide moiety. This polysaccharide includes 4 monosaccharides, and thus satisfies the requirements of claim 3. In addition, the polysaccharide has R3 as GM2 as shown in Table 1 of claim 4, and the heterologous lipid carrier is ganglioside GM2 as recited in claim 5.
Li teaches chitosan as an adjuvant for use in cancer vaccines (p. 1,. Title). Li teaches that chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine (p. 1, Abstract, lines 2-3). Li teaches that the immune response induced by chitosan is determined by the existence of antigen, and that i.p. administration of chitosan alone has been found to enhance humoral responses but not cell-mediated immune responses in mice (p. 3, paragraph bridging left and right columns, lines 1-5).
Moreover, Li teaches that studies of chitosan as an adjuvant for subcutaneous vaccination of mice with 𝛽-galactosidase, a model protein antigen, enhanced antigen-specific antibody titers over fivefold and antigen-specific splenic CD4+ proliferation over sixfold. Li teaches that increases in antibody titers together with robust delayed-type hypersensitivity (DTH) responses revealed that chitosan induced both humoral and cell-mediated immune responses, and was equipotent to incomplete Freund’s adjuvant and superior to aluminum hydroxide (p. 3, right column, first full paragraph, lines 1-13).
Li teaches that because of its mucoadhesive properties, chitin and chitosan are widely applied for mucosal routes of administration, including administration via oral, nasal, and ocular mucosa. Li teaches that the enhancement of adaptive immune responses to several antigens has been shown, and clinical studies have confirmed that chitosan is a promising adjuvant platform for intranasal vaccination. Li teaches the mechanisms of vaccine enhancement by chitosan through mucosal administration are believed to be due to both retention of vaccine in the nasal passages via mucoadhesion and opening of endothelial cell junctions for paracellular transport of vaccine (p. 3, left column, first paragraph, lines 1-11).
Finally, Li teaches the structure of chitosan as including glucosamine monosaccharides linked by only β-1,4 bonds (p. 3, Figure 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to formulate the vaccine of Livingston with chitosan as an adjuvant. One of ordinary skill in the art would have been motivated to formulate the vaccine of Livingston with chitosan as an adjuvant because Livingston teaches the benefits of vaccination with the cancer antigen ganglioside GM2, and because Li teaches the benefits of chitosan as an adjuvant for promoting an antigen-dependent response in cancer vaccines. Accordingly, because Livingston teaches a cancer vaccine that includes GM2, and because Li teaches the benefits of chitosan as an adjuvant in cancer vaccines, one of ordinary skill in the art would have considered the addition of chitosan to the vaccine of Livingston, because chitosan may improve the cell-mediated immune responses to GM2 and improve the efficacy of the vaccine taught by Livingston.
In addition, MPEP 2144.06 states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In this instance, because both GM2 and chitosan are recognized by the prior art for use in cancer vaccines, the composition comprising both GM2 and chitosan is prima facie obvious, because each are useful for the purposes of treating cancer by administering a cancer vaccine.
Moreover, because Li teaches that chitin and chitosan mucoadhesive properties, chitin and chitosan are widely applied for mucosal routes of administration, including oral routes, one of ordinary skill in the art would have recognized that the vaccine of Livingston formulated with chitosan as an adjuvant may be effective when administered via alternative routes of administration, such as orally, because chitosan’s mucoadhesive properties permit oral administration when used as an adjuvant.
Regarding the requirement of claim 1 that i) and ii) are associated by direct bonding to each other, because each of GM2 and chitosan would have been present in composition together, they would be expected to interact with each via non-covalent bonding, absent evidence to the contrary.
Regarding the requirements that i) and ii) do not restrict or influence each other’s movement by forming a membrane, and that at least part of i) and ii) is exposed and accessible to the environment, the prior art provides no suggestion that chitosan and GM2 would form a membrane or other structure. Therefore, GM2 and chitosan would be expected to be exposed and accessible to the environment, absent evidence to the contrary.
Regarding claim 8, because Li teaches chitosan as made up of glucosamine monosaccharides joined by only β-1,4 bonds, the use of chitosan as P1 would satisfy the requirements of claim 8.
Conclusion
No claims are allowed.
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/B.M.B./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693
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