CTNF 17/739,029 CTNF 89454 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Pursuant to a preliminary amendment filed December 2, 2025, claims 1-19 are currently pending in the instant application. Response to Election/Restriction Applicant's election without traverse of Group I, claims 1-7 and 9-19, directed to a method for studying or identifying a biologically active agent that binds to a membrane protein; and Applicant’s election of Species without traverse as follows: Species (A): wherein the 2D and/or 3D structures have been obtained from a saposin lipoprotein particle that has been obtained according to claim 2 (claim 2); Species (A)(I): further comprising providing a cell and/or a cell organelle; and lysing or disrupting the cell (claim 3); Species (B): wherein the biologically active agent is a chemical compound or a biological molecule (claim 9); Species (C): wherein the membrane protein is: (i) an integral transmembrane protein (claim 12); Species (D): wherein the particle essentially consists of at least one lipid binding polypeptide, etc. (claim 16); Species (E): wherein the lipid binding proteins is a saposin A, saposin B, saposin C, saposin D or a derivative thereof (claim 14); Species (E)(I): wherein the SAPLIP is selected from a protein having at least 80% sequence identity to the full length sequence of SEQ ID NOS: 1-6 (claim 14(i)); and Species (E)(II): SEQ ID NOS: 1, 2, 3, 4, 5 and 6 (claim 14), in the reply filed December 2, 2025 is acknowledged. Please Note: claim 19 depends from instant claim 14, wherein Applicant elected that the membrane protein is: (i) an integral transmembrane protein, in the reply filed 12-02-2025. Instant claim 19 depends from claim 14(iii), such that claim 19 will not be examined on the merits. Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Claims 4-7, 11, 13, 15, 17 and 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. Therefore, claims 1-3, 9, 10, 12, 14 and 16 are under consideration to which the following grounds of rejection are applicable. Priority The present application filed June 6, 2022, is a CIP of US Patent Application 16326545, filed February 19, 2019 (now US Patent 11346843), which is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2017/071043, filed August 21, 2017, which claims the benefit of European Application EP16184843.7, filed August 19, 2016. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed applications, US Patent Application 16/326545, filed February 19, 2019; PCT/EP2017/071043 (WO2018033647), filed August 21, 2017; and European Patent Application EP16184843.7, filed August 19, 2016, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; “obtaining one or more 2D and/or 3D structures of a saposin lipoprotein particle;” “modeling the binding of said biologically active agent…using said one or more 2D and/or 3D structures;” and/or “resolving the binding sites and interactions between…in the 2D and/or 3D structure.” Therefore, the priority date for the presently claimed invention is May 6, 2022 , the filing date of US Patent Application 17/739,029. Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 1 of the instant application. Claim Objections/Rejections Claim Interpretation: instant claims 2 and 3 are determined to be product-by-process claims. The structural elements of the 2D and/or 3D structure of instant claims 2 and 3 is interpreted to comprise: one or more 2D and/or 3D structures of a saposin lipoprotein particle, wherein the saposin lipoprotein particles of instant claims 2 and 3 are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. Moreover, even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe , 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113. Claim Objection 07-29-01 AIA Claim s 1, 2 and 14 are objected to because of the following informalities: Claims 1, 2 and 14 recite a mixture of pronouns including “the” and “said” within each claim, such that for consistency, a single pronoun reciting either “the” or “said” should be used . Appropriate correction is required. 07-29-01 AIA Claim s 1, 2 and 14 are objected to because of the following informalities: Claims 1, 2 and 14 recite the terms “2D,” “3D,” and "SAPLIP,” where an abbreviation should be spelled out in the first encounter of the claims . Appropriate correction is required. Specification Objection 07-29 AIA The disclosure is objected to because of the following informalities: the as-filed Specification, filed May 6, 2022, does not include the current status of US Patent Application No. 16/326,545 (now US Patent 11,346,843) . Appropriate correction is required. Drawing Objection The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference characters not mentioned in the description: Figure 4a : illustrates feature 6’, which is not identified in the as-filed Specification, filed May 6, 2022. 06-22-07 Figure 5 : illustrates features 10 and 11, which are not identified in the as-filed Specification, filed May 6, 2022. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 1-3, 9, 10, 12, 14 and 16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 1 is indefinite for the recitation of the term “the binding sites” such as recited in claim 1, line 7. There is insufficient antecedent basis for the term “the binding sites” in the claim. Claim 1 is indefinite for the recitation of the term “the 2D and/or 3D structure” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the 2D and/or 3D structure” in the claim because claim 1, line 3 recites the term “one or more 2D and/or 3D structures”. Claim 2 is indefinite for the recitation of the terms “the 2D and/or 3D structure is from a saposin lipoprotein particle” such as recited in claim 2, lines 1-2 because claim 2 depends from instant claim 1, wherein claim 1 does not recite that “the 2D and/or 3D structure is from a saposin lipoprotein particle.” Moreover, claim 1 is directed to a ‘method of using’ a saposin lipoprotein particle, while claim 2 appears to recite a ‘method of making’ a saposin lipoprotein particle, which is directed to a different invention than the invention elected by Applicant in the reply filed 12-02-2025 and, thus, the metes and bounds of the claim cannot be determined. Claim 2 is indefinite for the recitation of the terms “process;” “library of saposin lipoprotein particles;” “prepared;” “heterogenic mixture; “ “different membrane lipid and membrane protein compositions;” “membrane components;” “cell;” “cell or an organelle membrane;” “lipid binding polypeptide;” “saposin-like protein of lipid interacting proteins;” ”mixture of crude membrane vesicles;” “archaeal, eukaryotic or prokaryotic cell;” “organelle membrane;” “membrane lipids;” “liquid environment;” “membrane proteins embedded;” “membrane protein composition;” “starting material; “present and active in vivo,” etc. in claim 2, lines 2-18 because claim 2 depends from instant claim 1, where claim 1 does not recite that the terms listed supra and, thus, the metes and bounds of the claim cannot be determined. Claims 2 and 16 are indefinite for the recitation of the terms “the particle” and “the particles” such as recited in claim 2, lines 2-5 and 15-16. There is insufficient antecedent basis for the terms “the particle” and “the particles” in the claim because claim 1, lines 3 recites the term “a saposin lipoprotein particle”. Claim 2 is indefinite for the recitation of the terms “the SAPLIP,” “the crude cell or organelle membranes,” and “the lipids,” such as recited in claim 2, lines 7, 12 and 17. There is insufficient antecedent basis for the terms “the SAPLIP,” “the crude cell or organelle membranes,” and “the lipids” in the claim. Claim 2 is indefinite for the recitation of the term “one or more of said crude membrane vesicles” such as recited in claim 2, line 13. There is insufficient antecedent basis for the term “one or more of said crude membrane vesicles” in the claim because claim 2, line 9 recites the term “a mixture of crude membrane vesicles.” Claim 3 is indefinite for the recitation of the term “cell organelle” such as recited in claim 2, lines 3 and 4 because claim 3 depends from claim 1 and 2, wherein claims 1 and 2 do not recite the presence of a “cell organelle” and, thus, the metes and bounds of the claim cannot be determined. Claim 9 is indefinite for the recitation of the term “such as” such as recited in claim 9, line 2 because the term “such as” is similar to the word “like” when introducing examples, such that it is unclear what chemical compounds or biological molecules are “like” a (poly)nucleotide, a peptide, protein or antigen-binding portion thereof and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite a proper Markush grouping (e.g., selected from the group consisting of…). Claim 9 is indefinite for the recitation of the term “(poly)nucleotide” such as recited in claim 9, line 2 due to the use of use parentheses to comment on or qualify part of the sentences such as, for example, “(poly)”. It is unclear whether the limitation in parentheses is meant to be a limitation in the claims or whether it is only a suggestion, an example of a preferred embodiment, or a synonym. Accordingly, the metes and bounds of the claim are not clear. Claim 9 is indefinite for the recitation of the term “antigen-binding portion thereof” such as recited in claim 9, line 3 because claim 9 depends from instant claim 1, wherein claim 1 does not recite the presence of an antigen; and/or a biologically active agent comprising an antigen-binding portion. Moreover, it is unclear what portions of compounds and molecules “like” a (poly)nucleotide, a peptide, and protein is considered an “antigen-binding portion” and, thus, the metes and bounds of the claim cannot be determined. Claim 10 is indefinite for the recitation of the term “the biologically active agent is…an agent for cosmetic, diagnostic or research applications” such as recited in claim 10, lines 1-3 because claim 10 depends from claims 1 and 9, wherein claim 9 already recites that the ‘biologically active agent’ is a chemical compound or a biological molecules such as…or an antigen-binding portion thereof” and, thus, the metes and bounds of the claim cannot be determined. Claim 14 is indefinite for the recitation of the term “the lipid binding protein” such as recited in claim 14, line 1. There is insufficient antecedent basis for the term “the lipid binding protein” in the claim. Moreover, claim 14 depends from instant claim 1, wherein claim 1 does not recite the presence of a “lipid binding protein.” Claim 14 is indefinite for the recitation of the term “optionally” such as recited in claim 14, line 3 because what is “optional” is ambiguous including whether a derivative form is ‘optionally’ selected and/or whether a derivative form of the SAPLIP is ‘optionally’ selected from (i)-(iii). Moreover, it is unclear whether a derivative can be selected and, thus, the metes and bounds of the claim cannot be determined. Claim 14 is indefinite for the recitation of the terms “the derivative form of the SAPLIP” such as recited in claim 14, lines 3. There is insufficient antecedent basis for the terms “the derivative form of the SAPLIP” in the claim. Moreover, claim 14 depends from instant claim 1, wherein claim 1 does not recite the presence of a SALIP or a “derivative form of a SAPLIP.” Claim 14 is indefinite for the recitation of the terms “the full length sequence” and “the sequence” such as recited in claim 14, lines 4 and 10. There is insufficient antecedent basis for the terms “the full length sequence” and “the sequence” in the claim. Claim 14 is indefinite for the recitation of the term “a protein” such as recited in claim 14, lines 4, 6 and 10. There is insufficient antecedent basis for the terms “a protein” in the claim because claim 1, lines 1-2 recite the term “a membrane protein.” Claim 14 is indefinite for the recitation of the term “solubilized lipids” such as recited in claim 14, line 9 because claim 14 depends from claim 1, wherein claim 1 does not recite the presence of “solubilized lipids” and/or “employing solubilized lipids” in a process. Claim 14 is indefinite for the recitation of the term “the process” such as recited in claim 14, line 9. There is insufficient antecedent basis for the term “the process” in the claim. Claim 16 is indefinite for the recitation of the term “essentially consist of” such as recited in claim 16, lines 1-2 because it is unclear whether Applicant intends to use the transitional phrase or the alternative limitation “consisting essentially of” such as discussed in MPEP 2111.03 and 2173.05(h); or whether Applicant intends that the claim has some other meaning and, thus, the metes and bounds of the claim cannot be determined. Claim 16 is indefinite for the recitation of the terms “the at least one lipid binding polypeptide;” “the cell or organelle membrane;” and “the organelle membrane” such as recited in claim 16, lines 2-3. There is insufficient antecedent basis for the term “the cell or organelle” in the claim. Moreover, claim 16 depends from claim 1, wherein claim 1 does not recite the preparation of particles; and/or the presence of lipid binding polypeptides, cell membranes, membrane lipids, organelle membranes, membrane proteins of a cell or organelle membrane stemming from the cell or organelle membrane, preparing particles, etc. and, thus, the metes and bounds of the claim cannot be determined. Claim 12 is indefinite insofar as it ultimately depend from instant claim 1. Claim Rejections - 35 USC § 112(d) 07-36 AIA The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claims 2, 3, 9, 10, 14 and 16 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 recites (in part): “wherein the 2D and/or 3D structure is from a saposin lipoprotein particle…they are present and active in vivo” such as recited in claim 2, lines 1-18 because claim 2 depends from instant claim 1, wherein claim 1 does not recite that “the 2D and/or 3D structure is from a saposin lipoprotein particle” or the presence many of the components recited including a process; a library of saposin lipoprotein particles; membrane components; a cell or an organelle membrane; lipid binding polypeptides; a set of different saposin lipoprotein particles; archaeal, eukaryotic or prokaryotic cell heterogenic mixtures; SAPLIP family of lipid interacting proteins, etc. Thus, claim 2 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites (in part): “wherein the mixture of crude membrane vesicles in step a) is obtained by a. I) providing a cell and/or a cell organelle; and a.2) lysing or disrupting the cell and/or the cell organelle” in lines 1-4 because claim 3 depends from claim 1 and 2, wherein claims 1 and 2 do not recite the presence of a cell organelle. Thus, claim 3 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 9 recites (in part): “wherein the biologically active agent is a chemical compound or a biological molecule such as a (poly)nucleotide, a peptide, protein or antigen-binding portions thereof” in lines 1-3 because claim 9 depends from instant claim 1, wherein claim 1 does not recite the presence of antigens and/or any antigen-binding portions in the biologically active agent. Thus, claim 9 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 recites (in part): “wherein the biologically active agent is a pharmaceutically active agent…or an agent for cosmetic, diagnostic or research applications” in lines 1-3 because claim 10 depends from claims 1 and 9, wherein claim 9 already recites that the ‘biologically active agent’ is a chemical compound or a biological molecules such as…or an antigen-binding portion thereof.” Moreover, claim 1 and 9 do not recite any cosmetic, diagnostic or research applications. Thus, claim 10 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 14 recites (in part): “wherein the lipid binding protein is saposin A, saposin B, saposin C, saposin D or a derivative or truncated form thereof, and wherein, optionally, the derivative form of the SAPLIP is selected from…inserted and/or substituted” in lines 1-11 because claim 14 depends from claim 1, wherein claim 1 does not recite the presence of lipid binding proteins including derivatives or truncated forms of lipid binding proteins, SAPLIP, solubilized lipids, a process, etc. Thus, claim 14 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 16 recites (in part): “wherein the particles essentially consist of the at least one lipid binding polypeptide, membrane lipids and/or membrane proteins of the cell or organelle membrane stemming from the cell or the organelle membrane that was used to prepare the particles” in lines 1-4 because claim 16 depends from claim 1, wherein claim 1 does not recite the presence of lipid binding polypeptides, cell membranes, membrane lipids, organelle membranes, membrane proteins of a cell or organelle membrane stemming from the cell or organelle membrane, preparing particles, etc. Thus, claim 16 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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 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. 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 07-15 AIA Claim s 1-3, 9, 10, 12, 14 and 16 are rejected under 35 U.S.C. 102( a1)/102(a2 ) as being anticipated by Frauenfeld et al. (hereinafter “Frauenfeld”) (International Application WO2014095576, published June 26, 2014; EP 12197904.1, effective filing date December 18, 2012) as evidenced by Salipro-Biotech (SaliproBiotech, 2019, 1-4) . Regarding claims 1-3 , Frauenfeld teaches that the invention provides a nanoscale particle comprising a lipid binding polypeptide , lipids and a hydrophobic agent , wherein the hydrophobic agent is different from the lipids, and wherein the lipid binding polypeptide is a saposin-like protein or a derivative or truncated form thereof (interpreted as a saposin lipoprotein particle); as well as, a process for preparing a particle comprising a saposin-like protein or a derivative or truncated form thereof and lipids comprising the steps of: (a) contacting the saposin-like protein or a derivative or truncated form thereof with solubilized lipids in a liquid environment and (b) allowing for the self-assembly of the particle at a pH of from 5.0 to 10.0, wherein the invention provides a pharmaceutical composition comprising the particle of the invention for delivering a hydrophobic agent to an individual in need thereof and includes the use of the particle of the invention in preventing , treating or lessening the severity of a disease or its use in a diagnostic method , a cosmetic treatment , as hydrophobic agent delivery particle , as a tool for drug development , drug screening , membrane protein research or as vaccination formulation (interpreting the hydrophobic agent as an active agent bound to the saposin lipoprotein particle, claim 1) (Abstract). Frauenfeld teaches that the saposin-family comprises 4 small (~80 amino acids) proteins , saposin A to D , that bind and/or interact with lipids and function as essential cofactors for several lysosomal enzymes in sphingolipid catabolism (interpreted as saposin A, B, C and D) (pg. 3, lines 31-32; and pg. 4, lines 1-2). Frauenfeld teaches that the particle 1 of the invention is prepared by mixing purified lipid binding polypeptide 2 with lipids 3 and the hydrophobic organic compounds 4 to be incorporated and allowing the self-assembly of the particle 1 at a pH of from about 5.0 to about 10.0 (interpreted as a saposin lipoprotein particle comprising a membrane protein, and modeling the binding of an active agent to the membrane protein, claims 1-3) (pg. 52, lines 4-8; and Figure 2A). Figure 2A is shown below: PNG media_image1.png 230 912 media_image1.png Greyscale Frauenfeld teaches that superior lipoprotein particles with flexible and controllable size ranges featuring the ability to adapt to the respective size of the hydrophobic agent that is to be incorporated into the lipoprotein particles , wherein such particles shall allow for simple integration of membrane proteins and other hydrophobic components which, for example, can be pharmaceutically or biologically active compounds or diagnostic compounds (interpreted as modeling binding of active agents to membrane proteins in saposin lipoprotein particles including biologically active agents, claims 1-3) (pg. 7, lines 1-9). Frauenfeld teaches that the saposin-like protein-lipoprotein particles obtainable by the method of the invention (designated " Salipro particles " herein) differ from the particles of the prior art in multiple features, for example by their inherent size flexibility and ability to adapt to the respective size of the hydrophobic agent that is to be incorporated into the lipoprotein particles (interpreting Salipro particles and/or SAPLIP particles as the particles prepared in claims 2 and 3) (pg. 8, lines 22-29). Frauenfeld teaches that the invention provides a process for the manufacture of a particle comprising a lipid binding polypeptide and lipids , wherein the lipid binding polypeptide is a SAPLIP or a derivative or truncated form thereof, wherein the process comprises the steps of: (a) contacting the lipid binding polypeptide with solubilized lipids in a liquid environment ; and (b) allowing for the self-assembly of the particles at a pH of from 5.0 to 10 or 5.0 to 8.5; in particular from 6.0 to 8.0 and most preferably from 7.0 to 8.0 (interpreting SAPLIP particles as the particles prepared in claims 2 and 3) (pg. 36, lines 29-31; and pg. 37, lines 1-8). Frauenfeld teaches in Example 8 and Figure 14 that Salipro particles comprising eukaryotic membrane protein , purified Synaptphysin (SYP), were prepared (cf. Saposin+Lipids+MemPro SYP and Salipro-SYP in Figure 14) (interpreted as obtaining 2D and/or 3D structures of saposin lipoprotein particle comprising membrane protein, claims 1-3) (pg. 70, lines 26-28; and Figure 14). Frauenfeld teaches in Example 9 that curcumin was used as hydrophobic model drug for testing incorporation into Salipro particles using the method of the invention, wherein curcumin was primarily chosen because of its various pharmacologic implications (such as anti-cancer , anti-inflammatory , anti-oxidant and anti-proliferative activity ) and its fluorescence in lipid environments , such that using its UV-absorbance and fluorescence characteristics in a lipid environment, incorporation of curcumin into Salipro particles can easily be followed (interpreted as modeling the binding of a biologically active agent to the membrane protein in the particle using the one or more 2D and/or 3D structures, claims 1-3) (pg. 72, lines 16-25), where it is known that the classic Salipro technique can be applied to membrane proteins of all classes from a wide range of cell types, and the development of Direct Membrane Extraction allows the incorporation of membrane proteins from crude membranes into native lipid Salipro particles as evidenced by Salipro-Biotech (pg. 2, col 1, fourth and sixth full paragraphs) Frauenfeld teaches in Figure 15 , the incorporation of curcumin into the Salipro particles of the invention as indicated by the presence of both an absorption peak at 280 nm and a fluorescence peak at the exact position where the characteristic Salipro-protein absorption peak is present (interpreting as binding the biologically active agent to said membrane protein in the saposin lipoprotein particle and resolving the binding sites and interactions, claims 1-3) (pg. 73, lines 13-25). Frauenfeld teaches that Saposin C is capable of inducing membrane fusion of phospholipid-containing vesicles in an acidic environment (Archives of Biochemistry and Biophysics 2003 Jul 1; 415(1) 43-53), a feature not exhibited by the other saposins in Qi et al. (2009) Clin Cancer Res 15 (18) :5840-5851 report on saposin C-coupled dioleoylphosphatidyl-serine nanovesicles (SapC-DOPS) that contain an aqueous interior, have a mean diameter of about 190 nm and show tumor-targeting activity in vivo (interpreted as particles where the membrane proteins are embedded in the lipids of the cell or organelle membrane used as starting material in which they are present and active in vivo; and SapC-DOPS as the particles of claim 1, claims 2 and 3) (pg. 4, lines 15-22). Regarding claim 9 , Frauenfeld teaches that the particle includes a targeting moiety attached to a lipid binding polypeptide or a lipid component, wherein the targeting moiety is selected from the group consisting of natural or synthetic ligands, antibodies and antibody fragments or other biomolecules suitable for targeting purposes (interpreting polypeptides as peptides, and antibodies as proteins, and synthetic ligands to include peptides and polynucleotides, claim 9) (pg. 20, lines 1-2 and 13-16). Frauenfeld teaches that the lipid binding polypeptide comprises a bioactive moiety selected from a drug , a cytotoxic agent, an enzyme , a label, a fluorophore , a contrast agent and a radiolabel (interpreting enzymes to include proteins, claim 9) (pg. 20, lines 18-21). Regarding claim 10 , Frauenfeld teaches that the hydrophobic agent can, for example, be a biologically active agent , a drug , an active ingredient of a drug , an active ingredient of a cosmetic product , an active ingredient of a plant protective product , a dietary and/or nutritional supplement, a diagnostic probe , a contrast agent, a label and/or an indicator (interpreting the hydrophobic agent as a biologically active agent including a cosmetic, an active ingredient in a drug, and diagnostic applications, claim 10) (pg. 25, lines 10-15). Regarding claim 12 , Frauenfeld teaches proteins comprising a hydrophobic moiety can be selected from a membrane protein , an integral transmembrane protein , an integral monotopic membrane protein , a peripheral membrane protein, an amphitropic protein in a lipid-bound state , a lipid-anchored protein and a chimeric protein with a fused hydrophobic and/or transmembrane domain (interpreting membrane proteins to be integral transmembrane proteins; and an amphitropic protein in a liquid-bound state, claim 12) (pg. 30, lines 8-13). Regarding claim 14 , Frauenfeld teaches that the SAPLIP is saposin A, B, C or D including a saposin selected from (Homo sapiens, Equus caballus, Bos taurus, Mus musculus, Oryctolagus cuniculus, Rattus norvegicus or Xenopus laevis) saposin A , saposin B , saposin C or saposin D , wherein the lipid binding polypeptide is a saposin-like protein (SAPLIP) or a derivative or truncated form thereof (interpreted as lipid binding protein is saposin A, B, C, D, claim 14) (pg. 15, lines 1-6 and 16-17). Frauenfeld teaches that the lipid binding polypeptide comprises the full length sequence of a SAPLIP including a derivative of a SAPLIP such as a polypeptide comprising an amino acid sequence with at least 20, 30, 40, 50 or 60 %, preferably at least 75 % identity to the full length sequence of the respective SAPLIP and/or a sequence having an identity with the full length sequence of a SAPLIP of at least 80 %, 85 %, 90 % or 95 % (interpreted as lipid binding protein is saposin derivative or truncated form thereof; and having 80% sequence identity to SEQ ID NOS: 1-6, claim 14) (pg. 16, lines 4-13). Regarding claim 16 , Frauenfeld teaches that Figure 4 depicts - in schematic form - the preparation as well as shape and molecular organization of Salipro particles 1 comprising an integral monomeric membrane protein 5 and hydrophobic organic compounds 4 according to the invention, depicted in (a) as side view and in (b) as top view, wherein the particle 1 of the invention is prepared by mixing purified SAPLIP 2 with lipids 3 , the membrane protein 5 and the hydrophobic organic compounds 4 to be incorporated and allowing the self-assembly of the particle 1 at a pH of from about 5.0 to about 10.0 (interpreting self-assembly as consisting essentially of a lipid binding polypeptide, membrane lipids and/or membrane proteins of the cell, claim 16) (pg. 54, lines 13-22). Frauenfeld teaches that when the particles of the invention are used as drug delivery vehicles , such a targeting moiety can serve to target the particles of the invention to a particular cell or tissue type, or to the infectious agent itself (interpreted as consisting essentially of a lipid binding polypeptide, membrane lipids and/or membrane proteins of the cell, claim 16) (pg. 19, lines 29-32). Frauenfeld meets all the limitations of the claims and, therefore, anticipates the claimed invention. Conclusion Claims 1-3, 9, 10, 12, 14 and 16 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMY M BUNKER/Primary Examiner, Art Unit 1684 Application/Control Number: 17/739,029 Page 2 Art Unit: 1684 Application/Control Number: 17/739,029 Page 3 Art Unit: 1684 Application/Control Number: 17/739,029 Page 4 Art Unit: 1684 Application/Control Number: 17/739,029 Page 6 Art Unit: 1684 Application/Control Number: 17/739,029 Page 7 Art Unit: 1684 Application/Control Number: 17/739,029 Page 8 Art Unit: 1684 Application/Control Number: 17/739,029 Page 9 Art Unit: 1684 Application/Control Number: 17/739,029 Page 10 Art Unit: 1684 Application/Control Number: 17/739,029 Page 11 Art Unit: 1684 Application/Control Number: 17/739,029 Page 12 Art Unit: 1684 Application/Control Number: 17/739,029 Page 13 Art Unit: 1684 Application/Control Number: 17/739,029 Page 14 Art Unit: 1684 Application/Control Number: 17/739,029 Page 15 Art Unit: 1684 Application/Control Number: 17/739,029 Page 16 Art Unit: 1684 Application/Control Number: 17/739,029 Page 17 Art Unit: 1684