DETAILED ACTION
Claims 1-3,5,7,10,14,16,20-26,28,30,37 and 41-42 are pending in the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application claims priority to the U.S. Provisional Application Serial No. 63/424,764 filed 11/11/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement was considered by the examiner. Please see attached initialed Forms 1449.
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-3, 5, 7, 10, 14, 16 and 41-42, drawn to a proteoliposome comprising phospholipid carrier and one or more protein embedded in the one or more phospholipid carrier.
Group II, claims 20-26, 28 and 30, drawn to a method of making a proteoliposome.
Group III, claim 37, drawn to a method of screening pharmaceuticals.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I, II, and III lack unity of invention because even though the inventions of these groups require the technical feature proteoliposome, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Yoshimura et al. (US 2009/0186364 A1).
Yoshimura discloses a method for preparation of recombinant proteoliposomes suitable for diagnostic applications; proteoliposomes are prepared by fusion of virus particles of a recombinant baculovirus, expressing a target membrane receptor (such as human thyroid-stimulating hormone receptor, acetylcholine receptor, insulin receptor, B1 adrenergic receptor, asialoglycoprotein receptor, etc.) with liposomes (Abstract). Liposomes are closed vesicles with lipid bilayers containing phospholipids; these phospholipids can be phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), diphosphatidylglycerol (cardiolipin), phosphatidic acid (PA), etc. ([0034-0036]). Yoshimura discloses that a phospholipid concentration of about 10 mM were obtained ([0092]). Yoshimura discloses protein embedded in the phospholipid layer (Fig. 2)
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Applicant’s Response
During a telephone conversation with attorney Roman Fayerberg on 3/4/2026 a provisional election was made without traverse to prosecute the invention of Group I, claims 1-3, 5, 7, 10, 14, 16, and 41-42. Affirmation of this election must be made by applicant in replying to this Office action. Claims 20-26, 28, 30 and 37 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Product-Process Rejoinder
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claim Rejections - 35 USC § 112(b)
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 14, 16, 21-26, 28, and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Above claims depend on previously canceled claims. A correction is required.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The specification does not define “similar proportions” as required in claim 1. The examiner cannot determine what level of similarity would satisfy this limitation.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. It is unclear as to what quantities are being compared. It is unclear whether the ratio refers to mass, molar amount, or another measurement.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim Interpretation
The instant specification defines placental proteoliposomes (PPLs) as phospholipid carriers with lipid and protein composition representative of placental trophoblast cells ([0004]).
Claims 1-3, 5, 10, 16, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshimura et al. (US 2009/0186364 A1), Deng et al. (US 2011/0064794 A1), Jang et al. (Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle, PNAS, 2012), and Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020).
Yoshimura discloses a method for preparation of recombinant proteoliposomes suitable for diagnostic applications; proteoliposomes are prepared by fusion of virus particles of a recombinant baculovirus, expressing a target membrane receptor (such as human thyroid-stimulating hormone receptor, acetylcholine receptor, insulin receptor, B1 adrenergic receptor, asialoglycoprotein receptor, etc.) with liposomes (Abstract). Liposomes are closed vesicles with lipid bilayers containing phospholipids; these phospholipids can be phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), diphosphatidylglycerol (cardiolipin), phosphatidic acid (PA), etc. ([0034-0036]). Yoshimura discloses that a phospholipid concentration of about 10 mM were obtained ([0092]). Yoshimura discloses protein embedded in the phospholipid layer (Fig. 2)
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Yoshimura discloses that the amount of budded virus and MLV added to 1 mL of the mixture were 10 ug protein ([0096]). Additionally, one of ordinary skill in the art would routinely experiment with different protein concentrations to optimize a proteoliposome.
Yoshimura does not explicitly mention ratio of phospholipid to protein.
Deng discloses a protein-phospholipid dispersion preparation in a drug delivery system, in which the weight ratio of protein to phospholipid is 1:300-300:1 (Abstract). The drug delivery system can be used to deliver nucleic acids ([0051]).
Jang discloses codelivery of syndecan-4 proteoliposomes with FGF-2 which increased the cellular uptake, trafficking, and nuclear localization of the growth factor. Syndecans are a family of single-pass transmembrane proteins (page 1679).
Bailey-Hytholt discloses a phospholipid composition with similar proportions of phospholipids as a naturally occurring cell type (lipid bilayers that mimic the composition of human placental trophoblast cells) (Abstract). Bailey-Hyholt discloses that the placenta plays a key role in regulating the maternal-fetal transport. Lipid bilayers inspired by the placenta can provide a facile new in vitro tool with promise for screening molecular transport across the important organ. Here we developed lipid bilayers that mimic the composition of human placental trophoblast cells – mass spectrometry identified five major lipid classes: PC, PE, PL, PS, and SPH (Abstract). The lipid composition was ~50% PC, ~23% PE, ~7% PI, ~9% PS, and ~11% SPH (Table 1). Ultimately, our work indicates that the cell-free placenta-inspired bilayers developed here can be useful for molecular interaction screenings (Conclusions).
Yoshimura discloses proteoliposomes with one or more transmembrane proteins embedded in the lipid bilayer. Deng discloses that a protein-phospholipid dispersion preparation can deliver nucleic acids. Jang discloses that the use of proteoliposome to deliver proteins and/or active ingredient is more effective. Bailey-Hyholt discloses that a phospholipid composition with similar proportions of phospholipids as a naturally occurring cell type is important to investigate the molecular interactions. Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to create a proteoliposome comprising one or more protein embedded in the phospholipid carrier, wherein the phospholipid carrier and the protein are developed to mimic the composition of human tissues or cells. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 2, the ratio of phospholipid to protein is discussed above.
Regarding claim 3, phospholipid carrier of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG) are discussed above.
Regarding claim 5, transmembrane protein is discussed above.
Regarding claim 10, delivering nucleic acid is discussed above.
Regarding claim 16, Jang discloses codelivery of syndecan-4 proteoliposomes with FGF-2. One of ordinary skill in the art would immediately envisage that a proteoliposome can be used to deliver transmembrane protein, fibroblast growth factor 2, or any other biologic entities as typically delivered by liposomes.
Regarding claim 41, placental proteoliposome is taught above.
Regarding claim 42, the phospholipid composition is taught above.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Yoshimura et al. (US 2009/0186364 A1), Deng et al. (US 2011/0064794 A1), Jang et al. (Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle, PNAS, 2012), and Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020) as applied to claims 1-3, 5, 10, 16 and 41-42 above, and further in view of Shin et al. (US 2017/0056555 A1).
Shin discloses a liposome for delivering an extracellular matrix, a method for promoting cell growth, and a method for preparing a liposome for delivering an extracellular matrix (Abstract). In accordance with an aspect of the present invention, there is provided a liposome for delivering an extracellular matrix, the liposome including: (a) a phospholipid membrane having an anionic lipid and a neutral lipid, which are self-assembled; and (b) an extracellular matrix bound to the anionic lipid by ionic boding to be disposed on a surface of the anionic lipid ([0011]). The present inventors endeavored to develop a liposome that is capable of promoting cell attachment and growth by delivering the extracellular matrix to cells ([0007]).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined proteoliposomes with ECM to promote cell attachment and growth. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Yoshimura et al. (US 2009/0186364 A1), Deng et al. (US 2011/0064794 A1), Jang et al. (Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle, PNAS, 2012), and Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020) as to claims 1-3, 5, 10, 16 and 41-42 above, and further in view of Angel et al. (US 2021/0009505 A1).
Angel discloses novel cationic lipids and their use in delivering nucleic acids to cells (Abstract). The amount of nucleic acid can be from about 0.5 mg/mL to about 50 mg/mL ([0415]).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have included one or more nucleic acid within a proteoliposome at a concentration taught above. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN SEUNGJAI KWON whose telephone number is (571)272-7737. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615