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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 5, 6, 9, 10, 14-20, and 29-30 in the reply filed on 6/4/2026 is acknowledged.
Priority
Priority to US 63/169,696, filed 4/1/2021, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 8/15/2024 and 7/31/2025, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1, 5, 6, 9, 10, 14-20, 29-31, and 34-36, filed 6/4/2026, are pending. Claims 1, 5, 6, 9, 10, 14-20, and 29-30 are under examination. Claims 31 and 34-36 are withdrawn.
Claim Interpretation
Regarding claim 20, the phrase “The liposome of claim 19, wherein the spider toxin has an amino sequence that is at least…” is interpreted to mean “The liposome of claim 19 wherein the spider toxin consists of an amino acid sequence that is at least…”.
This is supported by the specification at [0087]: “"Hybrid+2" or "U+2 peptide" or "U+2 protein" or "U+2 toxin" or "U+2" or "U+2-ACTX-Hvla" or "Spear" all refer to a U-ACTX-Hvla having an additional dipeptide operably linked to the native peptide. The additional dipeptide that is operably linked to the U peptide is indicated by the "+2" or "plus 2" can be selected from among several peptides, any of which may result in a "U+2 peptide" with unique properties as discussed herein. In some preferred embodiments, the dipeptide is "GS"; an exemplary U+2-ACTX-Hvla peptide is set forth in SEQ ID NO: 1.”
This indicates that SEQ ID NO: 1 is the complete spider toxin.
Specification
The disclosure is objected to because of the following informalities.
Appropriate correction is required.
The use of the term “Sephadex” in para [0370], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Triton X-100” in para [0370], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 31, and 34-36 are objected to because of the following informalities.
Claims 31 and 34-36 should have the status identifier of “Withdrawn” and currently, claim 31 has “Previously Presented” and 34-36 have “Original”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 20 recites a genus of spider toxins that can be 80% identical to SEQ ID NOs: 1-5 and 8. In the case of the shortest amino acid of 37 residues, this allows for 0.2 * 37 = 7 substitutions. This allows for a minimum sequence space of 20^7= 1.28 * 10^9 sequences.
In this case, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), a "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
As described above, claim 20 recites a huge sequence space of polypeptides.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
Applicant discloses SEQ ID NOs: 1-5 and 8, but does not provide any information on where these substitutions are allowed.
At the time the invention was made, the level of skill for preparing peptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptides that yield polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure (length) provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what peptide with a particular set of properties would look like structurally.
Applicant discloses six examples. This is a tiny fraction of the claimed sequences, however. Therefore, the provided examples only represent a limited structural diversity.
Since only a limited number of species of peptides are taught within the claimed genus above, the instant claim above fails the written description requirement. A representative number of species has not been taught to describe this genus. Regarding the peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every polynucleotide molecule recited by claim 1.
Claim 20 is rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 9, 10, 14-19, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Kennedy et al. (WO 2013/134734, published 9/12/2013) in view of Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1. (Kennedy et al., claim 1).
Kennedy does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of Kennedy with the lecithin liposome of Geho to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47).
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over Kennedy et al. in view of Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Kennedy et al. (WO 2013/134734, published 9/12/2013) in view of Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
PNG
media_image1.png
254
701
media_image1.png
Greyscale
(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
PNG
media_image2.png
523
701
media_image2.png
Greyscale
(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Kennedy et al. (WO 2013/134734, published 9/12/2013) in view of Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 9, 10, 14-19, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,669,319, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, the ‘319 patent discloses an insecticidal peptide with an ICK domain in claim 1: “A polypeptide comprising a plant Endoplasmic Reticulum Signal Peptide (ERSP) operably linked to one or more ICK insecticidal venom peptides (“ICK insecticidal peptides”), wherein the ICK insecticidal peptides are one or more of: a U-ACTX polypeptide, a Kappa-ACTX polypeptide, an Omega-ACTX polypeptide, or combinations thereof, and wherein said plant ERSP is the N-terminal of said polypeptide.”
The ‘319 patent does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘319 patent with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,669,319, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘319 patent, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘319 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
PNG
media_image1.png
254
701
media_image1.png
Greyscale
(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘319 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
PNG
media_image2.png
523
701
media_image2.png
Greyscale
(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘319 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,669,319, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘319 patent, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘319 patent in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Claims 1, 9, 10, 14-19, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,567,381 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, the ‘381 patent discloses an insecticidal peptide with an ICK domain in claim 1: “A composition comprising two types of insecticidal peptides wherein one type of insecticidal peptide is a Pore Forming Insecticidal Protein (PFIP), and the other type of insecticidal peptide is a Cysteine Rich Insecticidal Peptide (CRIP) wherein said CRIP is an artificial Inhibitor Cysteine Knot (ICK) motif peptide, wherein said ICK peptide is selected from one or any combination of the group of peptides comprising: SEQ ID NO: 650, SEQ ID NO: 651 and SEQ ID NO: 652, and said PFIP is selected from any combination of known Bt toxic peptides.”
The ‘381 patent does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘381 patent with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,567,381, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘381 patent, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘381 patent, Kennedy, Geho, and Papahahadiopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
PNG
media_image1.png
254
701
media_image1.png
Greyscale
(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘381 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
PNG
media_image2.png
523
701
media_image2.png
Greyscale
(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘381 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,567,381, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘381 patent, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘381 patent in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Claims 1, 9, 10, 14-19, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,472,854 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, the ‘854 patent discloses an insecticidal peptide with an ICK domain in claims 1-3:
“1. A method of increasing the yield of an insecticidal peptide in a recombinant yeast cell, comprising: operably linking a dipeptide to the insecticidal peptide by adding the codons for the dipeptide to the 5′ end of the transgene nucleotide sequence encoding the insecticidal protein and expressing the resultant dipeptide-insecticidal protein in said yeast cell;
wherein a C-terminus of the dipeptide is operably linked to an N-terminus of the insecticidal peptide;
wherein said dipeptide has one polar amino acid and one non-polar amino acid;
wherein operably linking the dipeptide to the insecticidal peptide converts the insecticidal peptide into a high-production (HP) peptide; and
wherein converting the insecticidal peptide into the HP peptide results in an increased yield of the HP peptide, compared to a yield of the insecticidal peptide before conversion, when said HP peptide or insecticidal peptide are recombinantly expressed in a yeast cell culture expression system.
2. The method of claim 1, wherein the insecticidal peptide is a Cysteine Rich Insecticidal Protein (CRIP).
3. The method of claim 2, wherein the CRIP is an Inhibitor Cystine Knot (ICK) motif protein or a non-ICK CRIP.”
The ‘854 patent does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘854 patent with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,472,854, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘381 patent, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘854 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
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(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘854 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
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701
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(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘854 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,472,854, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘854 patent, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Claims 1, 9, 10, 14-20, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,410,218 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, the ‘218 patent discloses SEQ ID NO: 5, an insecticidal peptide which is identical to Applicant SEQ ID NO: 1:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 41
# Identity: 41/41 (100.0%)
# Similarity: 41/41 (100.0%)
# Gaps: 0/41 ( 0.0%)
# Score: 244.0
#
#
#=======================================
1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
#---------------------------------------
#---------------------------------------
Claim 1 of the ‘218 patent recites: “1. A combination comprising a Bt toxin selected from the group consisting of: Cry1a, Cry1b, Cry1c, Cry2a, and combinations thereof, and a U+2-ACTX-Hv1a peptide having the amino acid sequence set forth in SEQ ID NO: 5, wherein the Bt toxin and the U+2-ACTX-Hv1a peptide are not fused together as a single fusion protein, wherein the combination is formulated in separate compositions, and wherein the separate compositions of the combination come together and have insecticidal activity.”
The ‘218 patent does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘218 patent with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘854 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 20, claim 19 is obvious as described above. The ‘218 patent discloses SEQ ID NO: 5, an insecticidal peptide which is identical to Applicant SEQ ID NO: 1:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 41
# Identity: 41/41 (100.0%)
# Similarity: 41/41 (100.0%)
# Gaps: 0/41 ( 0.0%)
# Score: 244.0
#
#
#=======================================
1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
#---------------------------------------
#---------------------------------------
Consequently, claim 20 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘218 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,410,218, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘218 patent, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘218 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
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254
701
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(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘218 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
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523
701
media_image2.png
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(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘218 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claims 1, 9, 10, 14-19, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,535,653 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
Regarding claim 1, the ‘653 patent discloses an insecticidal peptide that is a CRIP:
“1. A cleavable insecticidal or nematicidal polypeptide (CINP) comprising one or more cleavable peptide linkers (Linkers) said CINP having an Endoplasmic Reticulum Signal Peptide (ERSP) operably linked to the N-terminus of a construct comprising: (Linker-TP)n; (Linker-TP)n-Linker; (TP-Linker)n; or Linker-(TP-Linker)n; wherein the TP is a toxic protein, and n is an integer ranging from 2 to 200; and wherein the one or more Linkers has an amino acid sequence selected from the group consisting of: SEQ ID NOs: 1603, 1605, 1619, 1621, 1628, 1658, 1660, 1674, 1676, and 1683.
2. The CINP of claim 1, wherein the TP is a protein selected from the group consisting of a Pore Forming Insecticidal Protein (PFIP) and a Cysteine Rich Insecticidal Protein (CRIP).
The ‘653 patent does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘653 patent with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,535,653 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘653 patent, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘653 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
PNG
media_image1.png
254
701
media_image1.png
Greyscale
(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘653 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
PNG
media_image2.png
523
701
media_image2.png
Greyscale
(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘653 patent, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,525,653, in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998) and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘653 patent, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘653 patent in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Claims 1, 9, 10, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 7, 9, 32-34, and 37-43 of copending Application No. 18/642377 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the ‘377 application discloses an insecticidal peptide in claim 1: “An Av3 variant polypeptide having insecticidal activity against one or more insect species, wherein the Av3 variant polypeptide comprises SEQ ID NO: 4.”
The ‘377 application does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘377 application with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘377 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘377 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘377 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘377 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘377 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 7, 9, 32-34, and 37-43 of copending Application No. 18/642377 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 5, claim 1 is obvious as described above.
The ‘377 application, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘377 application, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
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254
701
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(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘377 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
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523
701
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(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘377 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claims 1, 9, 10, 14-19, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77-101 of copending Application No. 19/099,249 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the ‘249 application discloses a cysteine-rich protein in claim 1:
“A chimeric cysteine-rich protein (CRP), or an agriculturally acceptable salt thereof, comprising a disulfide bond scaffold according to Formula (II), Formula (IV), or Formula (VI);…”
The ‘249 application does not specifically disclose insecticidal proteins or peptides which are encapsulated in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1, which are cysteine rich proteins (Kennedy et al., claim 1). Kennedy also discloses the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the cysteine rich protein of the ‘249 application with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides. Furthermore, Kennedy discloses that cysteine rich proteins may be CRIPs, cysteine-rich insecticidal proteins.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77-101 of copending Application No. 19/099,249 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘249 application, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘653 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
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254
701
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(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘249 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
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523
701
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(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘249 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77-101 of copending Application No. 19/099,249 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘249 application, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘249 application in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Claims 1, 9, 10, 14-19, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/272,257 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, the ‘257 application discloses an insecticidal peptide that is a CRIP in claim 1:
“A protein comprised of an Endoplasmic Reticulum Signal Peptide (ERSP) operably linked to a Cysteine Rich Insecticidal Protein (CRIP) such as an Inhibitor Cysteine Knot (ICK) motif protein wherein said ERSP is the N-terminal of said protein (ERSP-ICK).”
The ‘257 application does not specifically disclose encapsulating insecticidal proteins or peptides in liposomes comprising lecithin.
However, Kennedy et al. (WO 2013/134734, published 9/12/2013) discloses insecticidal peptides and proteins: “New insecticidal proteins, nucleotides, peptides, their expression in plants, methods of producing the peptides, new processes, production techniques, new peptides, new formulations, and combinations of new and known organisms that produce greater yields than would be expected of related peptides for the control of insects are described and claimed.” (Kennedy et al., para. [0005]).
Kennedy also discloses the insecticidal protein CRIP in claim 1 (Kennedy et al., claim 1) and the need for such insecticidal peptides: “The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007]).
Furthermore, Geho et al. (EP0473645B1, published 3/18/1998) discloses the usage of lecithin for forming liposomes:
“In this example, a lecithin is first polytroned and then microfluidized or sonicated to create very large multilamellar liposomes. Although a separate step may be employed, it has been found practical to carry out a simultaneous reaction by including in the mixture of lecithin and aqueous media, a burden such as DEET. The DEET molecule possesses hydrophobic (lipid seeking) groups such as the ethyl moiety and the paramethylbenzene rings. The lipid seeking nature of the DEET molecule allows it to seek and penetrate a large multilamellar liposome so that the lipid domain of the liposome actually is disrupted and penetrated by the DEET molecule. The capture of the DEET molecule is illustrated in the five-step illustration in the drawing, which are reproductions of actual images from electron miscroscopy. The small black spot represents a particle of DEET and the multilamellar rings represent a larger liposome.” (Geho et al., col. 3, line 32).
Geho also discloses that usage of these liposomes is contemplated for insecticides that include peptides: “US 4,241,046 discloses liposomes comprising bioactive substances, including insecticides. Exemplified are liposomes encapsulating peptides, nucleic acids and bacteria.” (Geho et al., col. 2, line 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the insecticidal protein of the ‘257 application with the lecithin liposome of Geho for the purposes disclosed by Kennedy to arrive at the claimed invention because Geho discloses the usage of lecithin liposomes to encapsulate insecticides.
A person of ordinary skill in the art would be motivated to make this combination to achieve the slow release delivery system described by Geho: “It is an object of this invention to provide a slow release delivery system for an insect repellent or insecticide which is soluble in an organic solvent, by sequestering the chemical in a bipolar vesicle, and to provide a target molecule for such sequestered agent, the target molecule being selected to have affinity for stratum corneum.” (Geho et al., col. 1, line 47). Furthermore, Kennedy describes the need for insecticides: ““The global security of food produced by modern agriculture and horticulture is challenged by insect pests. Farmers rely on insecticides to suppress insect damage, yet commercial options for safe and functional insecticides available to farmers are diminishing through the removal of dangerous chemicals from the marketplace and the evolution of insect strains that are resistant to all major classes of chemical and biological insecticides. New insecticides are necessary for farmers to maintain crop protection.” (Kennedy et al., para. [0007].
A person of ordinary skill in the art would have a reasonable expectation of success because Papahadjopoulos et al. (US 4,241,046, published 12/23/1980), referenced above by Geho, discloses that: “Representative of material which may be encapsulated by the method of the invention are pharmaceutically active compounds and compositions thereof, carbohydrates, nucleotides, polynucleotides (both naturally occurring and synthetic) pesticides, including fungicides, insecticides, miticides, nematocides and mollusicides, water soluble fertilizers and agricultural nutrients, peptides, proteins, enzymes, viruses and the like. (Papahadjopoulos et al., col. 2, line 45, emphasis added). Therefore proteins were known to be able to be encapsulated by liposomes such as lecithin.
Consequently, claim 1 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 9, claim 1 is obvious as described above. Claim 9 further recites the case wherein the encapsulated insecticidal protein or agriculturally acceptable salt thereof has a greater bioavailability when ingested by a pest when compared to an equivalent amount of the insecticidal protein or agriculturally acceptable salt thereof when not encapsulated in the liposome and is ingested by the pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 9 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the greater bioavailability is a greater oral bioavailability in an insect pest selected from a lepidopteran pest, and a coleopteran pest.
Regarding the functional nature of this claim, The Patent and Trademark Office is not equipped to experimentally confirm such specific claims.
However, MPEP 2112.01(II) states: "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, the obvious liposome of claim 1 necessarily possesses the claimed activity unless evidence to the contrary can be presented.
Consequently, claim 10 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 14 claim 1 is obvious as described above. As disclosed above, Kennedy discloses the insecticidal protein CRIP as part of the composition of claim 1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the CRIP protein of Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulos because Kennedy discloses that CRIP is an effective insecticide: “This invention describes how to produce toxic insecticidal peptides in plants so they fold properly when expressed by the plants. It describes how to produce peptides in high yields in laboratory and commercial production environments using various vectors. It describes one class of toxic insecticidal peptide we call CRIPS which stands for Cysteine Rich Insecticidal Peptides (CRIPS). It describes another class of toxic insecticidal peptides we call PFIPS which stands for Pore Forming Insecticidal Proteins (PFIPS). And it describes how novel and synergistic combinations of CRIPS and PFIPS can be fashioned together and used for a variety of purposes, including the protection of crops against of Bt or Bacillus thuringiensis peptide resistant insects. We disclose how to make and use combinations of CRIPS and PFIPS to kill and control insects, even Bt resistant insects, at every low doses.” (Kennedy et al., para. [0016]).
Consequently, claim 14 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 15, claim 1 is obvious as described above. Kennedy discloses that the insecticidal protein may be a CRIP, but more specifically, an ICK motif protein in claim 6:
“6. A peptide of claim 1 operably linked to a Translational Stabilizing Protein (ST A), wherein said ERSP is the N-terminal of said protein and a Translational Stabilizing Protein (STA) may be either on the N-terminal side of the CRIP, which is optionally an ICK motif protein (ERSP-STA-ICK) ; or Non-ICK motif protein (ERSP-STA- Non-ICK) or on the C- terminal side of the ICK or Non-ICK motif protein (ERSP-ICK-STA) or ( ERSP- Non-ICK - STA).” (Kennedy et al., claim 6).
Furthermore, Kennedy discloses that the ICK protein may be that of the Australian Blue Mountain Funnel-web Spider (Hadronyche versuta) or Atrax robustus: “A composition where the CRIP is a ICK and optionally, said ICK is derived from, or originates from , Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus, including toxins known as U-ACTX polypeptides, U-ACTX-Hv l a, rU-ACTX-Hvla, rU-ACTX-Hvlb, or mutants or variants.” (Kennedy et al. para. [0019]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use an ICK protein from Hadronyche versuta or Atrax robustus as disclosed by Kennedy in the liposome of Kennedy, Geho, and Papahadjopoulous because Kennedy describes the efficacy of the ICK domain protein for insecticidal purposes:
“We explain that Bt protein and the insecticidal CRIP, ICK and or TMOF peptide are applied such that they work together, but they do not have to be applied at the same time. The PFIP like a Bt protein and the insecticidal CRIP, ICK and or TMOF peptide can be are applied concurrently or sequentially.” (Kennedy et al. para. [0620]).
Arachnids such as Hadronyche versuta or Atrax robustus are arthropods
Consequently, claim 15 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 16, claim 15 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 16 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 17 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 18, claim 17 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 18 is obvious over the ‘249 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 19, claim 18 is obvious as described above. The ICK proteins disclosed by Kennedy are from arachnids such as Hadronyche versuta or Atrax robustus.
Consequently, claim 19 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 29, claim 1 is obvious as described above. Kennedy describes the usage of excipients: “We explain that one, two or all Bt, ICK and TMOF peptides are derived from more than 1 different types or bacterial strain origins of one, two or all Bt, ICK and TMOF peptides with all the strains of one, two or all Bt, ICK and TMOF peptides contributing more than at least 1 % of the peptides from each strain type in said composition. The total concentration of Bt and CRIP peptide in the composition is selected from the following percent concentrations: t , 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99 %, or any range between any two of these values, and the remaining percentage of the composition is comprised of excipients.” (Kennedy et al., para. [0623]).
Consequently, claim 29 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Regarding claim 30, claim 29 is obvious as described above. Kennedy discloses an agricultural composition and a formulation of a dust:
“The pesticide compositions described may be made by formulating either the bacterial cell, crystal and or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, desiccated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term "agriculturally-acceptable carrier" covers all adjuvants, inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in pesticide formulation technology; these are well known to those skilled in pesticide formulation.” (Kennedy et al. para. [0505]).
Consequently, claim 30 is obvious over the ‘257 application in view of Kennedy et al., Geho et al. and Papahadjopoulos et al. and rejected.
Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/272,257 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 1 above, and further in view of Gharib et al. (Gharib, Riham, et al European Journal of Lipid Science and Technology 122.5: 1900402 (2020)).
Regarding claim 5, claim 1 is obvious as described above.
The ‘257 application, Kennedy, Geho, and Papahadjopoulos do not specifically disclose the case wherein the lecithin is a hydrogenated soy lecithin, although Papahadjopoulos does disclose the usage of soy lecithin: “The round-bottom flask described in Example 1, supra., is charged with 50p moles of soybean lecithin (Asolectin, Associated Concentrates, Woodside, New York) and 50p moles (3-sitosterol in chloroform.) (Papahadjopoulos et al., col. 10, line 24).
Gharib discloses the usage of hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine), with soybean phosphatidylcholine being soy lecithin:
“Hydrogenated phospholipon 90H (90% soybean phosphatidylcholine, 4% lysophosphatidylcholine, 2% triglycerides, 2% water, 0.5% ethanol, 1% iodine) was supplied by Lipoid GmbH (Ludwigshafen, Germany). “ (Gharib et al., page 2, col. 2, para. 1).
Gharib uses this soy lecithin to create liposomes for insecticides:
“In this paper, we demonstrated a successful freeze-drying of Euc loaded Phospholipon 90H liposomes where the characteristics of hydrogenated-liposomes (size, pdI, zeta potential, and morphology) were maintained after freeze-drying using HP-β-CD as cryoprotectant for CL and DCL systems. HP-β-CD/Euc and Euc-DCL controlled drug release and displayed a good stability after 6 months of storage at 4 °C in powder form. These results revealed that freeze-dried CD/drug inclusion complex and DCL reduced the volatilization of Euc and improved its retention. This work suggests that the encapsulated Euc could be considered as a suitable approach for the insecticide application.” (Gharib et al., page 8, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the hydrogenated soy lecithin disclosed by Gharib to produce the liposome of the ‘653 patent, Kennedy, Geho, and Papahadjopoulous because Gharib discloses the usage of hydrogenated soy lecithin for production of liposomes to encapsulate insecticides, which is also the goal of Kennedy, Geho, and Papahadjopoulous.
A person of ordinary skill in the art would be motivated to use hydrogenated soy lecithin because Gharib successfully creates a variety of liposomes which have a high encapsulation efficiency:
PNG
media_image1.png
254
701
media_image1.png
Greyscale
(Gharib et al., page 4, Table 1).
A person of ordinary skill in the art would have a reasonable expectation of success because Gharib successfully encapsulates an insecticide in their liposomes as described above and also because Papahadjopoulous already discloses the usage of soy for liposome generation.
Consequently, claim 5 is obvious over the ‘257 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Gharib discloses hydrogenated soy lecithin liposomes of sizes ranging from 169-208 nm. Individual examples in Gharib Table 2 directly read on the recited range of Applicant claim 6, while taken together, they substantially overlap:
PNG
media_image2.png
523
701
media_image2.png
Greyscale
(Gharib et al., page 4, Table 2).
MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”.
Consequently, claim 6 is obvious over the ‘257 application, Kennedy et al , Geho et al., and Papahadjopoulous et al. as applied to claim 1 above, and further in view of Gharib et al. and rejected.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/272,257 in view of Kennedy et al. (WO 2013/134734, published 9/12/2013), Geho et al. (EP0473645B1, published 3/18/1998), and Papahadjopoulos et al. (US 4,241,046, published 12/23/1980) as applied to claim 19 above, and further in view of Tedford et al. (US 2010/0081619, published 4/1/2010).
Regarding claim 20, claim 19 is obvious as described above.
Kennedy discloses SEQ ID NO: 11, a peptide with 95.8% identity to Applicant SEQ ID NO:1, but also includes additional amino acids:
Query Match 95.9%; Score 234; Length 305;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||
Db 267 QYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 305
However, Tedford discloses SEQ ID NO: 119, which matches exactly:
SQ Sequence 41 AA;
Query Match 100.0%; Score 244; Length 41;
Best Local Similarity 100.0%;
Matches 41; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
|||||||||||||||||||||||||||||||||||||||||
Db 1 GSQYCVPVDQPCSLNTQPCCDDATCTQERNENGHTVYYCRA 41
This sequence is specifically recited by Tedford claim 18:
“18. The process of claim 17 wherein said peptide is selected from any of the following sequences: SEQ ID NO: 60, SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119.”
Furthermore, Tedford discloses that SEQ ID NO: 119 is a good candidate for potency enhancement: “As noted above, many peptides are suitable candidates as the subject of the process to make special. The sequences noted above, below and in the sequence listing are especially suitable peptides that can be made special, and many of these have been made special according to this invention with the results shown in the examples below.” (Tedford et al., para. [0053]). SEQ ID NO: 119 is one such sequence listed in this section of Tedford.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use any of the listed spider toxins in Tedford para. [0053] in the liposome of the ‘257 application, Kennedy, Geho, and Papahadjopoulos because Tedford describes these peptides as being derived from Hadronyche versuta or Atrax robustus: “Toxins isolated from plants and insects, especially toxins from spiders, scorpions and plants that prey on or defend themselves from insects, such as, funnel web spiders and especially Australian funnel web spiders, including toxins found in, isolated from or derived from the genus Atrax or Hadronyche, including the genus species, Hadronyche versuta, or the Blue Mountain funnel web spider, Atrax robustus, Atrax formidabilis, Atrax infensus including toxins known as “atracotoxins,” “co-atracotoxins,” “kappa” atracotoxins, “omega” atracotoxins also known as ω-atracotoxin, U-ACTX polypeptides, U-ACTX-Hv1a, rU-ACTX-Hv1a, rU-ACTX-Hv1b, or mutants or variants.” (Tedford, et al., para. [0050]).
Consequently, claim 20 is obvious over the ‘257 application in view of Kennedy et al., Geho et al., and Papahadjopoulous et al. as applied to claim 19 above, and further in view of Tedford et al. and rejected.
Conclusion
No claim is allowed.
Claims 1, 5, 6, 9, 10, 14-20, and 29-30 are rejected.
Claims 31 and 34-36 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
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