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WO 2015/101625 Al 9 July 2015 (09.07.2015) W P O P C T

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WO 2015/101625 Al 9 July 2015 (09.07.2015) W P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/101625 Al 9 July 2015 (09.07.2015) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 8/36 (2006.01) A61K 9/50 (2006.01) kind of national protection available): AE, AG, AL, AM, A61L 27/14 (2006.01) A61K 31/20 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61Q 19/00 (2006.01) A61K 31/355 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 8/85 (2006.01) A61K 31/375 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61Q 19/08 (2006.01) A61P 17/02 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, A61K 8/11 (2006.01) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (21) International Application Number: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, PCT/EP2014/079448 SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 30 December 2014 (30. 12.2014) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (26) Publication Language: English TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (30) Priority Data: TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 13 199866.8 31 December 201 3 (3 1. 12.2013) EP DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (71) Applicant: PB&B SA [CH/CH]; EPFL Innovation Park, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Batiment C, CH-1015 Lausanne (CH). GW, KM, ML, MR, NE, SN, TD, TG). (72) Inventors: AHO, Anthony Youri; Rue Caroline 17, CH- Published: 1003 Lausanne (CH). SANDEEP, Raghunathan; Rue de — with international search report (Art. 21(3)) la barre 6, CH-1006 Lausanne (CH). — before the expiration of the time limit for amending the (74) Agent: Kasche & Partner AG, Resirain KASCHE, Andre; claims and to be republished in the event of receipt of 1, CH-8125 Zollikerberg (CH). amendments (Rule 48.2(h)) (54) Title: CONTROLLED RELEASE FATTY ACID COMPOSITIONS FOR USE IN BODY RECONSTRUCTION AND BODY- SHAPING (57) Abstract: The present invention is directed to compositions comprising physiologically acceptable, metabolic lipids, and physiologically acceptable, preferably biodegradable controlled release (CR) compounds, wherein the lipids are cell-free and the CR compounds release the metabolic lipids over a delayed time period under physiological conditions. In addition, the present invention relates to the use of such a composition for producing a cosmetic or therapeutic composition, preferably for fat tissue expansion or fat tissue repair. Also, the invention pertains to a method for the therapeutic or cosmetic treatment of a mammal comprising the ad - mimstration of the composition of the invention and preferably injecting the composition while withdrawing the injection needle un- til the tissue area of interest is treated. CONTROLLED RELEASE FATTY ACID COMPOSITIONS FOR USE IN BODY RECONSTRUCTION AND BODY-SHAPING The present invention is directed to compositions com prising physiologica lly accepta ble, meta bolic lipids, and physiologica lly accepta ble, prefera bly biodegrada ble controlled release (CR) compou nds, wherein the lipids are cell-free and the CR-com pounds release the meta bolic lipids over a delayed time period under physiologica l conditions. In addition, the present invention relates to the use of such a composition for producing a cosmetic or thera peutic composition, prefera bly for fat tissue expa nsion or fat tissue repair. Also, the invention pertains to a method for the thera peutic or cosmetic treatment of a mamma l comprising the ad ministration of the com position of the invention and prefera bly injecting the composition while withd rawing the injection need le until the tissue area of interest is treated . Background of the invention Fat tissue stores energy, provides insulation and defines exterior structura l features, for exa mple in the face, breasts, buttocks or any other form-defining body parts of mam mals. Next to cosmetic desires there are also thera peutic applications for fat tissue engineering and reco n struction, e.g. breast reconstruction after mastectomies, HIV-induced lipid dystrophy and facia l reconstruction after trau ma. Traditiona l methods for treating fat tissue defects and for cosmetic tissue augmentation employ a filling materia l that replaces or adds volume to the targeted body part. The filling materia ls are classified as autologous fillers and non-autologous fillers. Autologous fat tra nsfer, i.e. su rgica l fat cell isolation from one part and re-injection into another part of the body, has been practiced since the late 19th century. Autologous fat cell tra nsfer to the face has the adva ntage of its permanent nature and the autologous fat based injections result in a more soft and glowing look of the rejuvenated face. On the other hand, a major drawback is the unpredictability of the results due mostly to varying surviva l rates of adipose cells after injection. For exa mple, for fat cells injected into fat tissue areas (e.g. face or breasts) 30-70% die, mainly because of the absence of nutrients and oxygen in the pre-a ngio- genic state. Another problem is the surviva l of the fat cells during isolation. This issue has been improved by a number of techniques such as the use of aspirated need les and specia lized treatment of the isolated fat cells. A further drawback of this technique is that it requires surgi ca l intervention and adequate amounts of autologous fat cell materia ls, which is not available for many individua ls. A more modern course of action in fat tissue engineering is the injection of adipose derived stem cells (ADSC) that cause proliferation of new adipocytes. However, the process involves a lengthy, complicated and expensive procedure including liposuction, isolation of ADSC from the adipose cells by specia lized ultracentrifugation, optiona lly with the treatment of the isolated ADSCs with differentiating factors, and reinjection of differentiated cells into the desired t arget tissue. Because of the cell surviva l issue of fat cells various non-cellula r filler materia ls were envisaged . Collagen was the most widely used filler in the market till the emergence of hya lu ronic acid in 2003. Collagen induces mild immunogenic reactions because of its bovine source and this technology ca me t o an end with the emerging awa reness of the risk of bovine spongi form encepha lopathy (BSE) . Hya luronic acid (HA) has been used as an off prescription fat tissue filler for yea rs even though it was FDA approved much later in 2003. It has become the most domina nt filler on the market. Modern commercia l HA is high ly crosslinked with divinyl sulfone- based compounds for increased half-life and of recombina nt rather tha n anima l source for reducing immunity. The principle drawback of HA is its limited life spa n after injection. Most HA- based fillers endure for 3 t o 12 months only. As with silicon-based impla nts, the use of HA for breast enhancement ca n interfere with mammogra phy-based ca ncer detection. Other potentia l issues related t o HA are a higher frequency and risk of gra nuloma development, nodule formation and masta lgia, impla nt palpa bility, ca psula r contraction, superficia l infections and abscess development. Loca l and systemic ad minstration of estrogens has also been known t o increase women ' s breast size by estradiol receptor induction of adipose tissue generation. Spironolactone has been known t o induce breast development and feminization due t o its anti-a nd rogen properties. Another approach for the de-novo adipose tissue generation is the long-term loca l delivery of insulin and insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) by PLGA/PEG microspheres and this has been tested in an in vivo rat model (Yuksel et al., Plastic & Reconstructive surgery, vol. 105(5), April 2000, 1712 - 1720), wherein insulin- and IGF-1- containing microspheres were ad ministered directly t o the deep muscula r fascia of the rat abdomina l w all t o evaluate their potential for the de novo adipose tissue generation via adipogenic differentiation from non-adipocyte cell pools. The microspheres function as controlled release (CR) compou nds that provide for a long-term loca l delivery of the proteins that induce the de novo generation of adipose tissue at the ad ministration site. In summary, the prior art techniques for treating fat tissue defects and for cosmetic fat tissue augmentation require either the autologous transfer of fat cells or adipose derived stem cells (ADSC), the local administration of non-cellular non-permantent fillers or, alternatively, the local administration of adipocyte differentiation and growth factors. It is the objective of the present invention t o provide a composition for treating fat tissue defects and for cosmetic fat tissue augmentation that is technically easy t o produce and administer, that requires minimal surgical intervention and that is safe and cost efficient.
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