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 .
Response to Amendment
Applicant’s response of 06/12/2026 has been received and entered into the application file. Claims 1-3,7,10,14,16 and 41-42 are pending in this application.
Applicant’s amendments to the Specification and claims have overcome 112(b) rejection previously set forth in the Non-Final Office Action mailed 03/12/2026.
Claim Rejections - 35 USC § 103 (necessitated by amendment)
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, 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), Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020), and Hsieh et al. (US 2018/0092846 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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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). Bailey-Hytholt discloses that the overall goal of the work was to develop cell-free in vitro lipid bilayer models that mimic the lipid composition of the placental trophoblast cell (pg 31100, left col, 2nd paragraph).
Hsieh discloses proteo-microparticles such as proteoliposomes comprising a microparticle (e.g., liposome) and platelet membrane proteins, wherein the proteoliposomes are used for delivering a therapeutic agent (Abstract). The proteo-microparticles are platelet-like proteoliposomes (PLPs), which refers to liposome-like vehicles having one or more platelet membrane proteins inserted ([0028]). Hsieh teaches that platelet membrane proteins include SLC transporter and transmembrane protein (page 13, Table 2). Hsieh discloses that the platelet membrane proteins may comprise one or more proteins listed in Table 2, for example those that are involved in interaction with circulating blood cells, such as monocytes. In some examples, the PLPs described contains a mixture of membrane proteins isolated from platelets ([0043]). One of ordinary skill in the art would immediately envisage that depending on the desired function of the proteoliposome, one would experiment with protein proportions comparable to naturally occurring cell type.
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. Hsieh discloses that a proteoliposome can have transmembrane proteins such as SLC embedded within the particle membrane. 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 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), Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020) Hsieh et al. (US 2018/0092846 A1) as applied to claims 1-3, 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), Bailey-Hytholt et al. (Placental Trophoblast-Inspired Lipid Bilayers for Cell-Free Investigation of Molecular Interactions, acsami, 2020) Hsieh et al. (US 2018/0092846 A1) as to claims 1-3, 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.
Response to Arguments
Applicant’s arguments filed 06/12/2026 have been fully considered and a new reference Hsieh is incorporated to teach the newly added limitation.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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