METHOD OF APPLYING AN INJECTABLE FILLER
`Won‘zman et al.
`
`Appl. No.: Unknown Atty Docket: MEDC/.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Wortzman et al.
`
`Appl. No.: Unknown Atty Docket: MEDC/.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Won‘zman et al.
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`Appl. No; Unknown Atty Docket: MEDC/.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Wortzman et al.
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`Appl. No..' Unknown Atty Docket: MEDC/.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Won‘zman et al.
`
`Appl. No.: Unknown Atty Docket: MEDCI.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Won‘zman et al.
`
`Appl. No.: Unknown Atty Docket: MEDC/.049PR
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`METHOD OF APPLYING AN INJECTABLE FILLER
`Wortzman et al.
`
`Appl. No.: Unknown Atty Docket: MEDCI.049PR
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`Page 7
`
`
`
`

`

`MEDCI.O49PR
`
`PROVISIONAL PATENT
`
`METHOD OF APPLYING AN INJECTABLE FILLER
`
`BACKGROUND OF THE INVENTION
`
`Field of the Invention
`
`[0001]
`
`Methods and systems for using dermal fillers are disclosed.
`
`
`Description of the Related Art
`
`[0002]
`
`A variety of methods and substances exist for adding volume or firmness to
`
`a subject or subject’s face for cosmetic purposes. Despite the fact that such methods are
`
`being used With ever increasing frequency, the art has seen little in the way of developments in
`
`regard to certain aspects of these treatment methods.
`
`SUIVJMARY OF THE INVENTION
`
`[0003]
`
`In some aspects, the present disclosure provides a method for maintaining
`
`and/or prolonging injectable filler composition efficacy. This can be especially relevant to
`
`increase the aesthetic benefit of implanted materials.
`
`[0004]
`
`In some aspects, the present disclosure provides a method of injecting an
`
`injectable filler such as hyaluronic acid (HA) so that it provides longer lasting, superior, or
`
`longer lasting and superior benefits.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0005]
`
`FIG.
`
`1
`
`is a schematic depicting a protocol
`
`for a study involving
`
`comparison of a re-treatment session after 4.5 months with re-treatment session after 9
`
`months.
`
`[0006]
`
`FIG. 2 is a table outlining the schedule of procedures for a trial study
`
`involving comparison of a re-treatment session after 4.5 months With re-treatment session
`
`after 9 months.
`
`[0007]
`
`FIG. 3 is a bar graph summarizing results from a trial study. The bar graph
`
`shows a comparison of the percent of responders that received a re-treatment session at 4.5
`
`months to the percent of responders that received a re-treatment session after 9 months.
`
`Page 8
`
`-1-
`
`Page 8
`
`

`

`[0008]
`
`FIG. 4 is a line graph summarizing results from a trial study. The line
`
`graph shows a comparison of the improvement resulting from re-treatment at 4.5 months with
`
`re-treatment after 9 months at the indicated time points.
`
`[0009]
`
`FIG. 5 is a line graph summarizing results from a trial study. The line
`
`graph shows a comparison of wrinkle severity from re-treatment at 4.5 months with re-
`
`treatment after 9 months at the indicated time points.
`
`[0010]
`
`FIG. 6 is a line graph summarizing results from a trial study. The line
`
`graph shows a comparison of the improvement resulting from re-treatment at 4.5 months with
`
`re-treatment after 9 months at the indicated time points. The data used to prepare the curves
`
`represents the completers subset of the data.
`
`[0011]
`
`FIG. 7 is a line graph summarizing results from a trial study. The line
`
`graph shows a comparison of the improvement resulting from re-treatment at 4.5 months with
`
`re-treatment after 9 months at the indicated time points. The zero time in the graph represents
`
`the time immediately following the re-treatment time.
`
`[0012]
`
`Throughout the figures, the same reference numerals and characters, unless
`
`otherwise stated, are used to denote like features, elements, components or portions of the
`
`illustrated embodiments. Moreover, while the subject matter of this application can now be
`
`described in detail with reference to the figures, it is done so in connection with the illustrative
`
`embodiments.
`
`It is intended that changes and modifications can be made to the described
`
`embodiments without departing from the true scope and spirit of the subject invention as
`
`defined in part by the appended claims.
`
`DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
`
`[0013]
`
`It has now been realized that the standard method of adding volume or
`
`firmness to a subject by administering a dermal filler (for example, via a single administration),
`
`while adequate for some purposes, has various shortcomings. The present disclosure provides
`
`various methods for administering dermal fillers to subjects.
`
`It has now been discovered that
`
`repeated administration of certain dermal fillers not only provides the continued benefit that
`
`would be expected from repeated applications over a particular time period, but results in
`
`surprisingly superior results for that time period and beyond. For example, practicing some of
`
`Page 9
`
`-2-
`
`Page 9
`
`

`

`the embodiments described herein can prolong the effectiveness of the injectable filler beyond
`
`what would simply be expected from two independent applications of an injectable filler.
`
`In
`
`addition,
`
`in some embodiments,
`
`the timing of the re-treatment session can allow one to
`
`maintain more of the benefits from the injectable filler for a longer period of time.
`
`In some
`
`embodiments, the combination of an initial treatment session and an appropriately timed re-
`
`treatment session can provide synergistic results.
`
`[0014]
`
`In some embodiments, the disclosed methods involve applying an injectable
`
`filler to correct areas or locations that appear to lack volume or are “under volume,” and, at a
`
`subsequent time (as a separate application), re-treating the area with the injectable filler
`
`composition.
`
`In some embodiments, re-treatment can slow the rate of resorbtion of the
`
`injectable filler after re-treatment.
`
`In some embodiments, re-treatment can slow the rate of
`
`resorbtion of the injectable filler after re-treatment by maintaining tissue expansile tension.
`
`Thus, in some embodiments, the re-treatment procedure can provide results lasting for at least
`
`13.5 months if not longer.
`
`In some embodiments, little or no loss of volume is observed after
`
`about 18 months after initial treatment.
`
`[0015]
`
`In some embodiments, re-treatment can be performed, for example, prior
`
`to the occurrence of an unfavorable change in wrinkle severity in the treated area. One
`
`advantage of such an embodiment is that a substantial increase to a subject’s baseline wrinkle
`
`severity can be avoided throughout a longer duration of time. Thus, in some embodiments, it
`
`has been appreciated that the timing of the re-treatment schedule can be such that one can
`
`reduce decreases or losses in a first treatment’s effectiveness, while still providing for a second
`
`treatment (the “re-treatment”) in a sufficient period of time to allow for the enhanced duration
`
`of effectiveness of the treatment.
`
`[0016]
`
`It has also been appreciated that many traditional techniques do not take
`
`full advantage of the characteristics of volumetric fillers.
`
`Thus, some of the disclosed
`
`embodiments are useful in allowing one to improve the results of treatment with injectable
`
`filler.
`
`In some embodiments, re-treatment provides continued improvement of volume and/or
`
`firmness.
`
`In some embodiments, the improvement is continual over a period of time up to
`
`about,
`
`for example,
`
`13 or 14 months after re-treatment.
`
`In some embodiments,
`
`the
`
`improvement is due at least in part to the stimulation of collagenesis. For example, re-
`
`Page 10
`
`'3'
`
`Page 10
`
`

`

`treatment can increase collagen production by fibroblasts. These, and additional aspects, are
`
`discussed in greater detail below.
`
`[0017]
`
`The present description first describes various terms used in describing
`
`various aspects described herein. A general description of various embodiments of the
`
`administration methods is then provided and is followed by a more detailed description of
`
`specific aspects of the methods and variations. An additional section regarding additional
`
`embodiments is then provided. Finally, examples of using the various methods are disclosed.
`
`Definitions and Various Embodiments
`[0018]
`“Injectable
`filler
`
`composition”
`
`and
`
`“injectable
`
`filler”
`
`includes
`
`a
`
`composition that can be administered through injection into or beneath the skin of a subject.
`
`The injectable filler composition should not be unduly problematic for the subject receiving
`
`the composition. As can be appreciated by one of skill in the art, there are a large number of
`
`compositions that can be used as a filler for various embodiments disclosed herein.
`
`In some
`
`embodiments, the fillers are dermal fillers.
`
`In some embodiments, the filler is selected from
`
`RESTYLANETM and PERLANE® dermal fillers. Examples of fillers include those disclosed
`
`in US. Pat. Nos. 5,633,001, 5,007,940, 5,827,937, 5,128,326, 5,399,351, and 5,143,724, as
`
`well as PCT Pub. No. W0 87/07898, all of which are herein incorporated by reference in their
`
`entireties.
`
`In some
`
`embodiments,
`
`the composition is
`
`a cross-linked biocompatible
`
`polysaccharide gel composition.
`
`In some embodiments, the composition is formed by forming
`
`an aqueous solution of a water soluble, cross-linkable polysaccharide; initiating a cross-linking
`
`of said polysaccharide in the presence of a polyfunctional cross-linking agent; sterically
`
`hindering the cross-linking reaction from being terminating before gelation occurs, an
`
`activated polysaccharide thereby being obtained; and reintroducing sterically unhindered
`
`conditions for said activated polysaccharide so as to continue the cross-linking thereof up to a
`
`viscoleastic gel.
`
`[0019]
`
`In some embodiments, the injectable filler is characterized by its source.
`
`In
`
`some embodiments, the source can be biologic and/or synthetic. Biologic injectable fillers can
`
`be those that are derived from a living organism. Synthetic injectable fillers can fiirther be
`
`divided into two groups, a) man-made fillers for which there is no biologic counterpart and b)
`
`Page 11
`
`'4-
`
`Page 11
`
`

`

`man-made substances for which there is a counterpart biologic.
`
`In some embodiments, the
`
`injectable filler can be characterized by the body’s ability to clear a product without external
`
`intervention (e.g., these can be biodegradable or nonbiodegradable).
`
`[0020]
`
`Examples of biologic, biodegradable fillers are those that include materials
`
`derived from organism, human, and/or animal tissues and/or products. Examples of such
`
`fillers include the following: hyaluronic acid (HA), (such as the following: avian HA, bovine
`
`HA, and human HA (e.g., RESTYLANETM injectable filler)) and collagen (such as collagen
`
`I, collagen II, collagen III, crosslinked and/or noncrosslinked, bovine, porcine, human, and
`
`autologous collagen.
`
`Additional examples of collagen based fillers include ZyplastTM
`
`(collagen derived from bovine tissue), Zyderm ITM (collagen derived from bovine tissue),
`
`Zyderm IITM (collagen derived from bovine tissue), EvolenceTM (porcine derived collagen),
`
`and FibrelTM (porcine derived collagen). As can be appreciated by one of skill in the art, in
`
`some embodiments, the injectable filler is self-replicating, and can include living cells (such as
`
`collagen-producing cells or fibroblasts). Thus,
`
`in some embodiments there are injectable
`
`fillers that are biological and are relatively long lasting or relatively “permanent.”
`
`[0021]
`
`Synthetic, biodegradable,
`
`injectable fillers include RADIANCETM and
`
`RADIESSETM (microspheres of at
`
`least calcium and phosphate ions)
`
`injectable fillers,
`
`polyacids and polyethers described in US. Pat. No. 7,192,984 (e.g., carboxymethyl cellulose
`
`(CMC) and polyethylene oxide), and LARESSETM (polymer, polyacid, and /or polyether,
`
`similar but not identical to HA type molecules).
`
`[0022]
`
`Synthetic, non-biodegradable, injectable fillers include injectable fillers that
`
`are not readily broken down in the body. Synthetic, non-biodegradable, injectable flllers can
`
`include injectable fillers that
`
`include a biologic component (and vice versa).
`
`In some
`
`embodiments, at least a portion of product cannot be significantly broken down by various
`
`body processes. Additional examples of synthetic non-biodegradable fillers include the
`
`following: ARTEFILTM (polymethylmethacrylate (PMMA) microspheres suspended in bovine
`
`collagen), ARTECOLTM (polymethylmethacrylate (PMMA) microspheres suspended in bovine
`
`collagen), polymethylmethacrylate (Plexiglas) in bovine collagen carrier, denatured, silicone,
`
`and various polymers, polyacids, and polyethers.
`
`In some embodiments, the carrier has rapid
`
`biodegradation. Of course, as can be appreciated by one of skill
`
`in the art,
`
`in some
`
`Page 12
`
`'5-
`
`Page 12
`
`

`

`embodiments, any one, combination, or ingredient of the above fillers can be combined with
`
`the other flllers (or alternative fillers) in various embodiments and for particular results.
`
`[0023]
`
`As can be appreciated by one of skill in the art, injectable fillers need not be
`
`categorized by both their source and their ability to stay or be cleared from the body. That is,
`
`some fillers can simply be biological,
`
`synthetic, biodegradable, or nonbiodegradable.
`
`Additionally, as can be appreciated by one of skill in the art, some injectable fillers can include
`
`parts or aspects of various combinations of the above or following substances.
`
`[0024]
`
`Examples of injectable fillers
`
`include a substance selected from the
`
`following: collagen, fat, human or animal derived collagen, bovine collagen, type I collagen,
`
`type II
`
`collagen,
`
`type III
`
`collagen, 3.5% bovine dermal collagen cross-linked by
`
`glutaraldehyde to form a latticework, natural human collagen,
`
`autologous collagen,
`
`polymethylmethacrylate microspheres (optionally suspended in bovine collagen), suspension
`
`of collagen fibers prepared from the subject’s tissue, human tissue collagen matrix derived
`
`from cadaveric dermis, the polyacids and polyethers described in US. Pat. No. 7,192,984
`
`(e.g., carboxymethyl cellulose (CMC) and polyethylene oxide), acellular human cadaveric
`
`dermis that has been freeze-dried, micronized acellular human cadaveric dermis that has been
`
`freeze-dried,
`
`cultured
`
`autologous
`
`fibroblasts,
`
`hyaluronic
`
`acid,
`
`non—animal-stabilized
`
`hyaluronic acid derivative, microspheres of calcium hydroxyl appetite suspended in an
`
`aqueous gel carrier, dextran beads suspended in hylan gel of nonanimal origin (e.g., 40— to 60-
`
`um in diameter), solubilized elastin peptides with bovine collagen, silicone, solubilized elastin
`
`peptides with bovine collagen, poly-L-lactic acid, Gore-Tex (PTFE), glycosylated collagen,
`
`PMMA,
`
`bone-forming
`
`calcium
`
`apatite,
`
`cultured
`
`human
`
`cells,
`
`expanded
`
`polytetrafluoroethylene (e-PTFE), softform® of ePTFE, and some combination thereof
`
`Further examples of injectable fillers include the following: AQUAMID® (comprising water
`
`and cross-linked polymers), ARTEFIL® (polymethylmethacrylate (PMlVIA) microspheres
`
`suspended in bovine collagen), Laresse® Dermal Filler (synthetic, biocompatible polymers,
`
`non-HA
`
`gel
`
`comprising
`
`absorbable
`
`medical
`
`polymers),
`
`ARTECOLL®
`
`(polymethylmethacrylate
`
`(PMMA) microspheres
`
`suspended
`
`in
`
`bovine
`
`collagen),
`
`BELOTERO®, BIO-ALCAMIDTM (synthetic
`
`reticulate
`
`polymer
`
`(poly-alkyl-imide),
`
`CAPTIQUETM (non-animal hyaluronic acid), COSMODERMTM (human collagen skin filler),
`
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`COMOPLASTTM CYMETRA®, autologen, dermalogen®, FASCIANTM (fascia), fascia, fat,
`
`hylaformTM (avian hyaluronic acid),
`
`IUVEDERM® (biosynthesized, non-animal hyaluronic
`
`acid), RADIESSETM (microspheres of at least calcium and phosphate ions), Sculptra® (poly-
`
`L-lactic
`
`acid
`
`(PLLA)),
`
`collagen,
`
`hyaluronic
`
`acid, RESTYLANETM, PERLANE®,
`
`ZYDERM®, ZYPLAST® (collagen derived from bovine tissue), Dermalive®, (hyaluronic
`
`acid and acrylic hydrogel particles), Dermadeep® (hyaluronic acid and acrylic hydrogel
`
`particles), Hydrafill®,
`
`Isolagen® (cultured autologous human fibroblasts), LaresseTM
`
`(carboxymethylcellulose (CMC) and polyethylene oxide (PEO)
`
`flller), PuragenTM (filler
`
`comprising double cross-linked hyaluron molecules), Reviderm® Intra (filler comprising
`
`flexible DEXTRAN micro-beads suspended in super-coiled,
`
`stabilized hyaluronic acid),
`
`SculptraTM (Formerly New-FillTM filler
`
`from poly-L-lactic acid), Teosyal, Surgiderm®
`
`(hyaluronic acid filler involving 3D hyaluronic acid matrix technology), Outline®, Anika®,
`
`Cosmetic tissue augmentation (CTA, from Anika), and combinations thereof.
`
`[0025]
`
`As can be appreciated by one of skill in the art, any of the above fillers or
`
`components thereof can include other materials, for example, anesthetic materials, including,
`
`without limitation, lidocaine, prilocaine, tetracaine, etc.
`
`[0026]
`
`“Volumetric filler” is a type of injectable filler composition. Volumetric
`
`fillers can be dermal
`
`fillers.
`
`In some embodiments,
`
`the volumetric filler is capable of
`
`crosslinking and/or
`
`is crosslinked.
`
`Crosslinked compositions allow the filler
`
`to have
`
`predictably no or minimal volume or substance loss on injection.
`
`In some embodiments they
`
`also provide predictable expansion or “swelling” with re-hydration on injection: swelling to no
`
`more than 10% volume increase; not “shrinking” or losing volume as some fillers that lose
`
`water uncrosslinked HA volumes; and/or have sufficient tensile compression resistance.
`
`In
`
`some embodiments, the volumetric filler involves microbead technology (e.g., as disclosed in
`
`US. Patent Numbers 5,633,001 and 5,007,040, herein incorporated by reference in their
`
`entireties).
`
`In some embodiments, this allows compression resistance.
`
`In some embodiments
`
`this allows for the composition to have the ability to resist displacement. Other fillers,
`
`described as “slurries,” can be used but can be prone to displacement (e. g., disclosed in US.
`
`Patent Nos. 5,143,724, 5,633,001, herein incorporated by reference in their entireties).
`
`In
`
`some embodiments, the filler has the biocompatibility and “feel” of tissue rather than boney
`
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`

`

`implants or sedimentary products that can feel hard. However, bony implant or sedimentary
`
`fillers can also be used in some embodiments.
`
`[0027]
`
`“Dermal filler” is a type of injectable filler composition. Dermal filler
`
`denotes that the filler is compatible for use in or under the skin. Dermal fillers can be
`
`volumetric fillers.
`
`[0028]
`
`In some embodiments, the methods described herein are used to alter the
`
`appearance of a subject’s face.
`
`In some embodiments, this alteration is purely an aesthetic
`
`alteration.
`
`In some embodiments, the alteration does not treat or adjust any deformity that the
`
`subject may have. For example, in some embodiments, the subject may simply want added
`
`volume to various areas of their face. As such, the application of filler will not necessarily be
`
`considered a treatment of the subject’s face in all embodiments. Additionally, the term “under
`
`volume” does not imply or require that there is necessarily a deformity in the subject’s face.
`
`Rather, it simply denotes that there appears to be less volume under the skin in one area than
`
`in another.
`
`In some embodiments, the filler and technique is applied as a treatment of a
`
`deformity in a patient. Such applications can be more specifically denoted by the recitation of
`
`the fact that a “deformity” is being “treated,” or by the fact that the subject is called a
`
`“patient.” Applications in which no deformity is being addressed can be more specifically
`,3 CL
`
`denoted by the use of the terms “non-treatment,
`
`subject-preference” or similar term. When
`
`such terms are not explicitly used, the techniques and aspects are generic to both treatment
`
`and non-treatment applications. As will be appreciated by one of skill in the art, the term
`
`“subject” encompasses “patient.”
`
`[0029]
`
`“Target area” as used herein refers to areas or locations to be treated with
`
`injectable filler composition, and includes areas or locations that appear to lack volume or are
`
`“under volume.”
`
`“Target areas” include locations of,
`
`for example, oral commissures,
`
`marionette lines, mandibular hollows, raise jowls, frowning mouth, pouty lower lip, lateral
`
`expression lines, mental creases, chin dimplings, zygomatic hollows, nasolabial furrows, tear
`
`troughs, and brow lifts.
`
`[0030]
`
`As noted above, the term “treatment” can denote a purely cosmetic result
`
`and one that can remove or reduce signs of aging.
`
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`[0031]
`
`In general,
`
`the term “initial
`
`treatment” denotes the application of an
`
`injectable filler to a location that does not currently retain a significiant amount of an
`
`exogenous injectable filler. As will be appreciated by one of skill in the art, an initial treatment
`
`can be performed to achieve a “fill correction” of a location.
`
`In some situations, this initial
`
`treatment can include a “touch-up” session, approximately one to two weeks after the initial
`
`injection session. As will be appreciated by one of skill in the art, the touch-up session is a
`
`step that
`
`is done as part of the initial
`
`treatment and performed to bring the subject’s
`
`appearance into filll correction. This is typically done after the swelling in the subject’s face
`
`has gone down (due to the initial application of the injectable filler) but before the benefits of
`
`the initial injections are lost. Generally, the term “initial treatment” will include both the initial
`
`injection(s) (or the “initial injection session”) and, if needed, a subsequent injection (or set
`
`thereof) described as a “touch-up” session. As will be appreciated by one of skill in the art,
`
`the touch-up session is designed to bring the treated area into full correction. Thus,
`
`in
`
`situations where the “initial application” of the dermal filler brings the area into full correction,
`
`no touch-up session is required.
`
`In addition,
`
`in some embodiments a touch-up session
`
`generally involves the application of a smaller amount of a dermal filler compared to the initial
`
`injections of the dermal filler. For example, in some embodiments, the volume of dermal filler
`
`applied during the initial injection session is more than 0.5 cc, for example, 0.5-0.6, 0.6-0.7,
`
`0.7-0.8, 0.8-0.9, 0.9-1, l-l.l, 1.1-1.2 cc or more (e.g., 1-2, 2-3, 3-4, 4-5 cc, or more). The
`
`volume of dermal
`
`filler applied during the touch-up session is generally less, e.g.,
`
`approximately 0.2 to 0.3, 0.3-0.4, 0.4-0.5, 0.5-0.6, 0.6-0.7 cc.
`
`[0032]
`
`The term “re-treatment” or “second treatment” session denotes an
`
`application of an injectable filler that is distinct from the initial treatment session (e.g., the
`
`initial injection session and, optionally, the touch-up session) and occurs following a full-
`
`correction of the location that the injectable filler is applied to. The re-treatment occurs after
`
`the filll correction has been achieved and in some embodiments,
`
`is performed prior to the
`
`complete degradation of the product from the initial treatment.
`
`In some embodiments, the re-
`
`treatment is applied two months after the initial treatment.
`
`In some embodiments, the re-
`
`treatment occurs following the degradation of the dermal filler from the initial treatment.
`
`In
`
`some embodiments, the re-treatment occurs 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-9, 9-10, 10-11, 11-
`
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`

`12 or more months following the initial treatment.
`
`In some embodiments, the re-treatment
`
`occurs following the initial treatment, but after the volume of the dermal filler that was applied
`
`to the subject as decreased,
`
`thereby allowing additional dermal filler to be added to the
`
`subject. While the volume can vary, the average volume applied for the re-treatment can be
`
`0.3 cc or greater, for example, 0.3-0.4, 0.4-0.5, 0.5-0.6, 0.6-0.7, 0.7-0.8, 0.9-1, l-l.l cc or
`
`greater.
`
`[0033]
`
`In some embodiments,
`
`the volume of the dermal
`
`filler for the initial
`
`injection session is greater than the volume used in the re-treatment session, which is greater
`
`than the optional volume used in the touch-up session.
`
`[0034]
`
`A “full correction” denotes that the volume desired has been achieved in
`
`the subject’s skin due to the presence of the dermal filler (e.g, excluding swelling from the
`
`application of the dermal fillers).
`
`Various Embodiments
`
`[0035]
`
`The present disclosure demonstrates that various re-treatment methods can
`
`result in effective treatment of target areas for 9 to 12 months and longer. Furthermore, it is
`
`disclosed herein that early re-treatment can be superior as patients do not experience an
`
`increase in wrinkle severity before receiving a second treatment and the response is maintained
`
`for at least 1 year.
`
`[0036]
`
`Some of the disclosed embodiments are useful for maintaining, prolonging,
`
`and/or improving the results of treatment with injectable fillers.
`
`In some embodiments,
`
`methods involve, for example:
`
`treating, with injectable filler, areas that appear to be “under
`
`volume” in a subject; optionally touching-up any areas as needed within, for example, one to
`
`two weeks of the initial treatment; and re-treating the subject with injectable filler at an
`
`appropriate interval following the initial treatment session. Such a method can greatly extend
`
`the duration of benefit obtained from an injectable filler. For example, in some embodiments,
`
`the use of a re-treatment step allows for the benefits to be extended for more than 6 months,
`
`e.g, 6-9, 9-12, 12-135 months or more.
`
`[0037]
`
`In some embodiments, the re-treatment step can occur relatively close in
`
`time to the initial treatment step so that subjects do not experience an increase in wrinkle
`
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`

`

`severity before receiving the re-treatment, which can still allow for the prolonged benefits of
`
`the dual treatment method. Without intending to be limited by theory, the dual treatment
`
`process is believed to maintain tissue expansile tension and slow gel resorption so that benefits
`
`and duration of effectiveness of the injections can be extended (and appear the same when
`
`comparing re-treatment durations of 4.5 months and 9 months, as described in the examples).
`
`[0038]
`
`In some embodiments, a subject can be treated with injectable filler to
`
`correct areas or locations that appear to lack volume or are “under volume,” and, at a
`
`subsequent time, the same areas or locations can be re-treated with injectable filler.
`
`In some
`
`embodiments, a third, fourth,
`
`fifth, or additional treatments with injectable filler can be
`
`performed.
`
`In various embodiments, a time course of treatments can be determined, for
`
`example, by evaluation of treatment outcome at various timepoints. The evaluation can be
`
`performed during, for example, follow-up sessions.
`
`[0039]
`
`The injectable fillers used can be any injectable filler suitable for correcting
`
`areas or location that appear to lack volume. Examples of injectable fillers are provided in the
`
`previous section and include, for example without limitation, volumetric fillers and dermal
`
`fillers.
`
`In some embodiments,
`
`the injectable filler can be, for example, RESTYLANETM
`
`dermal filler.
`
`In some embodiments, the injectable filler used for the initial treatment can be
`
`the same as the injectable filler used for re-treatment.
`
`[0040]
`
`In some embodiments, the injectable fillers used for the initial treatment and
`
`re-treatment are different.
`
`In cases where the injectable fillers used to re-treat is different
`
`from the injectable filler used for the initial treatment, the injectable fillers used to re-treat can
`
`improve the efficacy of the injectable filler used for the initial
`
`treatment.
`
`In some
`
`embodiments, the injectable filler comprises a compound that stimulates collagen synthesis. In
`
`some embodiments, the injectable filler comprises a compound such as hyaluronic acid (HA).
`
`[0041]
`
`In some embodiments, the initial treatment and the re-treatment employ a
`
`same or similar compound as the injectable filler.
`
`In some embodiments, the initial treatment
`
`employs an HA compound and the re-treatment employs an injectable filler.
`
`In some
`
`embodiments, the initial treatment employs an injectable filler and the re-treatment employs an
`
`HA compound.
`
`In some embodiments, the HA is 100,000 gel particles/ml filler.
`
`In some
`
`embodiments,
`
`the initial
`
`treatment and re-treatment employ injectable fillers that do not
`
`Page 18
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`

`

`include HA.
`
`In some embodiments the filler for the initial injection session and the touch-up
`
`session are the same type of injectable filler.
`
`In some embodiments the injectable filler for the
`
`initial injection session and the touch-up session are different types of injectable fillers.
`
`In
`
`some embodiments, the touch-up dermal filler is HA.
`
`In some embodiments, the filler for the
`
`initial treatment allows for expansion of the tissue while also being capable of being absorbed
`
`into the skin or degraded.
`
`[0042]
`
`Some of the indications which can be addressed by the systems and
`
`methods disclosed herein include: oral commissure, marionette lines, mandibular hollow, raise
`
`jowl, frowning mouth, pout lower lip, later expression lines, mental crease, chin dimpling,
`
`zygomatic hollow, nasolabial filrrow, tear trough, and brow lift.
`
`[0043]
`
`In various embodiments, the objective of the initial treatment can be to
`
`achieve a desired cosmetic result at the areas of treatment.
`
`In some embodiments, defects
`
`(i.e., areas or locations that appear to lack volume or are “under volume”) can be fillly
`
`corrected during an initial treatment session. The amount of correction may be ascertained by
`
`visual assessment of appearance of the defect.
`
`In some embodiments,
`
`the amount of
`
`correction can be deter