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
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, claim(s) 1-10, drawn to a method of differentiating mesenchymal stem cells (MSCs) to adipocytes.
Group II, claim(s) 11-18, drawn to a composition or an emulsion of a composition that includes vegetable lecithin at a concentration that is capable of differentiating MSCs to adipocytes.
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 and II lack unity of invention because even though the inventions of these groups require the technical feature of a composition (cell culture medium) that includes vegetable lecithin at an effective concentration for differentiating MSCs to adipocytes, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Bissell (U.S. Patent App. No. 2013/0259807 in view of Zhang et al. (Internl J Molecular Med, 2009, both cited in IDS filed on Feb. 29, 2024, as further explained below in the art rejection.
During a telephone conversation with Guy Levi on June 19, 2026 a provisional election was made with traverse to prosecute the invention of Group I, claims 1-10. Affirmation of this election must be made by applicant in replying to this Office action. Claims 11-18 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US2022/042161, filed Aug. 31, 2022. Applicant’s claim for the benefit of a prior-filed parent provisional application 62/238,961 filed on Aug. 31, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is Aug. 31, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Feb. 29, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 6 is objected to because of the following informalities: there is a (,) missing between myocytes and fibroblasts. Appropriate correction is required.
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.
Claim(s) 1 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Bissell et al. (U.S. Patent App. No. 2013/0259807 A1) in view of Zhang et al. (Internl J Molecular Med, 2009), both cited in IDS filed on Feb. 29, 2024.
The claims are directed to methods of “affecting differentiation” of mesenchymal stem cells (MSCs) to adipocytes through admixing a composition including vegetable lecithin into a growth medium including MSCs in a concentration operable to cause differentiation.
For the purpose of examination, the broadest reasonable interpretation of the claims is that the only the preparation of a culture medium (MSCs + growth medium + vegetable lecithin) is required. The claims do not require that the differentiation actually occurs.
Bissell et al. teach a method of screening agents for their ability to differentiate preadipocytes to adipocytes. (Abstract). More specifically, Bissell et al. teach screening of compounds which promote differentiation of mesenchymal stem cells to adipocytes. (paras. [0006], [0130]).
Bissell et al. does not teach screening a vegetable lecithin.
Zhang teaches the adipogenic activity of lecithin, finding that lecithin promoted adipocyte differentiation and differentiation-specific gene expression, and increased triglycerides and free fatty acid levels in the adipocytes (abstract). More specifically, Bissell et al. teach culturing 3T3-L1 (a cell line used as a model for adipocyte differentiation) and primary pre-adipocytes in a differentiation culture medium supplemented with various concentration of lecithin or in a culture medium (not differentiation) with various concentration of lecithin; both promoted differentiation to adipocytes. (pg. 449, 2nd col.; pg. 450, “Results”). Zhang et al. conclude that lecithin promotes adipocyte differentiation in a rapid and dose-dependent manner. (pg. 452, “Discussion”)
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the assay taught by Bissell et al. to incorporate using vegetable lecithin (as taught by Zhang et al.) and determining an appropriate concentration resulting in differentiation of MSCs to adipocytes because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because Bissell et al. teach a model for doing so and Zhang teach that lecithin is adipogenic; screening MSCs with vegetable lecithin to determine if and at what concentration it results in differentiation of MSCs to adipocytes would have been the next reasonable, non-inventive step, as it expected from the teachings in the art that this will readily work.
With respect to claim 6, Zhang et al. teach differentiation of 3T3-L1 cells to adipocytes. As the 3T3-L1 cell is a fibroblast cell, it would have been obvious to have chosen MSCs that were derived from fibroblasts, as doing so would closely replicate the teachings of Zhang et al.
With respect to claims 7 and 8, Zhang teaches the adipogenic effects ofthiozolidinedione (pg. 449, col 2, para 1 - "Activation of PPARy causes adipocyte differentiation and obesity in animals, while inhibition of PPARy results in the loss of adipocyte in mice (10-14).
Several PPARy agonists have been identified, including thiazolidinedione (TZD) and 15 deoxy-12,14 prostaglandin J2 (10,11), which stimulates 3T3-L1 adipocyte differentiation and causes weight gain in patients"), rendering the inclusion of it in medium for differentiating obvious.
With respect to claim 9, Zhang et al. teach the inclusion of lecithin in a differentiation medium, which contains 10 µg/mL of insulin. (pg. 449, “Materials and methods”).
Claim(s) 2, 3, 5 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over combination of Bissell et al. (U.S. Patent App. No. 2013/0259807 A1) and Zhang et al. (Internl J Molecular Med, 2009), both cited in IDS filed on Feb. 29, 2024, as applied to claims 1 and 6-9 above, and further in view of Kato et al. (U.S. Patent App. No. 2015/0267172 A1, cited in IDS filed on Feb. 29, 2024).
Bissell et al. as modified by Zhang et al. does not teach a lecithin solution including PBS, emulsifying the lecithin and the PBS solution, or emulsifying through sonication.
Kato et al. teach a composition including vegetable lecithin and PBS solution, where the solution is formed by emulsifying the lecithin and the PBS solution (para [0232]). Kato et al. teach a phospholipid composition with a concentration of 1 mg/ml that is ultrasonically emulsified. (para [0217]).
With respect to claims 2, 3 and 5, it would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Bissell et al. to incorporate a solution of lecithin with PBS and emulsifying it at the claimed concentration to form a continuous and dispersed phase and further sonicated the mixture because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating these modifications would have led to predictable results with a reasonable expectation of success because Kato et al. teach preparation of lecithin in this manner and it further would be expected that adjusting the concentration and emulsification would be within the routine optimization of one of ordinary skill in the art, as Zhang et la. teach that lecithin will promote differentiation and adjusting the preparation of the lecithin would be obvious absent additional considerations.
With respect to claim 10, Kato et al. teach a composition comprising lecithin and the beneficial effects of exogenous phosphatidylcholine on cell proliferation (para [0020]-[0021] - "For use in serum-free culturing of an animal cell, a culture medium additive of the present invention contains: at least three growth factors selected from the group consisting of FGF, PDGF, TGF-, and HGF; and at least one phospholipid. In the culture medium additive of the present invention, it is preferable that the phospholipid is selected from the group consisting of
phosphatidic acid, lysophosphatidic acid, phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, phosphatidyl choline, and phosphatidylglycerol"; para [0263]; para [0227] - "Animal-derived phospholipids (phosphatidic acid (PA) and phosphatidylcolin (PC)) were added to the base medium (the culture medium 3), thereby the culture medium 4 being prepared. With the use of the culture medium, a fine cell proliferation effect was obtained even under a serum-free condition"). It would have been obvious to one of ordinary skill in the art to apply the addition of phosphatidylcholine taught by Kato et al. to the method made obvious by Bissell, in view of Zhang to enhance cell proliferation wherein the ratio of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) in the lecithin is non-native due to excess PC.
Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over combination of Bissell et al. (U.S. Patent App. No. 2013/0259807 A1), Zhang et al. (Internl J Molecular Med, 2009), and Kato et al. (U.S. Patent App. No. 2015/0267172 A1, all cited in IDS filed on Feb. 29, 2024), as applied to claims 2, 3, 5 and 10 above and further in view of Ali et al. (U.S Patent App. No. 2010/0068251 A1, cited in IDS filed on Feb. 29, 2024).
Bissell et al., as modified by Zhang et al. and Kato et al., do not teach lecithin in a dispersed phase having an average particle size of between about 20 and 900 nm.
Ali et al. teach a lecithin emulsion comprising particles having a diameter between 20 nm and 900 nm (para [0147] "Tacrolimus (100 mg), Cholesteryl sulfate (60 mg), and Soy lecithin (3.94 g) were mixed together in water (70 mL) and homogenized using high pressure homogenizer. The resulting suspension was then filtered through 0.2 g filter and then mixed with 7.5% sucrose solution (30 mL) and lyophilized both in vials and in bulk. The particle size was determined using Nicomp particle sizer 380. The mean volume weighting diameter amounted to less than 200 nm").
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Bissell et al. to incorporate a solution of lecithin with PBS and emulsifying it at the claimed concentration to form a continuous and dispersed phase lecithin in a dispersed phase having an average particle size of between about 20 and 900 nm and further sonicated the mixture because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating these modifications would have led to predictable results with a reasonable expectation of success because Ali et al. teach preparation of lecithin in this manner and it further would be expected that adjusting the average particle size would be within the routine optimization of one of ordinary skill in the art, as Zhang et la. teach that lecithin will promote differentiation and adjusting the preparation of the lecithin would be obvious absent additional considerations.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TERESA E KNIGHT whose telephone number is (571)272-2840. The examiner can normally be reached Monday-Friday 9-4.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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