1
`
`UF.827P
`
`DESCRIPTION
`
`POLY (NON-CONJUGATED DIENE) BASED SUNSCREENS
`
`The subject invention was made with government support under a research project
`
`supported by National Science Foundation Private Investigator Grant, Contract No. DMR-
`
`0703261 and 0314110. The government hascertain rights to this invention.
`
`BACKGROUNDOF INVENTION
`
`10
`
`UV radiation penetrates the ozone layer over two wavelength regimes, UVB (290-
`
`320nm) and UVA (320-400nm). UVBacts directly on biological molecules, causing the familiar
`
`delayed sunburn that arises 12-24 hours after exposure, skin aging, skin cancer (melanoma) and
`
`eye photokeratities. UVA acts indirectly with the skin by forming reactive oxygen species,
`
`causing an “immediate” sunburn that diminishes within 2 hours after exposure. UVA potentially
`
`15
`
`plays a role in delayed sunburn and skin cancer. Although less energetic, UVA, which accounts
`
`for about 5.6% of sunlight, penetrates the skin more deeply, even into the dermis, than does UVB
`radiation, about 0.5% of sunlight, which generally is limited to the epidermis.
`Melanomahas experienced the most rapid increase in the numberof cases ofall forms of
`
`cancer with more than 51,000 cases reported in America each year. As most cases have been
`
`20
`
`attributed to sun exposure,
`
`the market for sunscreens presently exceeds $1 billion a year.
`
`Sunscreens are substances used to protect the skin by absorbing, reflecting and/or scattering
`
`damaging ultraviolet (UV) radiation. Sunscreens are typically used as a componentin a cream or
`
`lotion. Sunscreen formulations are an article intended for the prevention of a disease and are
`
`regulated as an over-the counter (OTC) drug.
`
`25
`
`In a Final Monograph of May 21, 1999, entitled “Sunscreen Drug Products for Over-The-
`
`Counter Human Use” by the U.S. Food and Drug Administration (FDA), conditions were
`
`established under which OTC sunscreen drug products are generally recognized as safe and
`
`effective and not misbranded as part of FDA’s ongoing review of OTC drug products. The
`
`Monograph established that an active ingredient of sunscreen products consists of any of the
`
`30
`
`following (within the concentration specified for each ingredient when the finished product
`
`provides a minimum SPF value of not
`
`less than 2 as measured by a testing procedures
`
`J\UF\827P\Application.doc\srv
`
`

`

`2
`
`UF.827P
`
`established in the Monograph): Aminobenzoic acid (PABA) (15%); Avobenzone (3%); Cinoxate
`
`(3%); Dioxybenzone (3%); Homosalate (15%); Menthyl anthranilate (5%); Octocrylene (10%);
`
`Octyl methoxycinnamate (7.5%); Octyl salicylate (5%); Oxybenzone (6%); Padimate O (8%);
`
`Phenylbenzimidazole sulfonic acid (4%); Sulisobenzone (10%); Titanium dioxide (25%);
`
`Trolamine salicylate (12%); and Zinc oxide (25%). Since 1999 Ecamsule (10%) and
`
`Phenylbenzimidazole sulfonic acid (4%) have been approved for use as sunscreens. Also
`
`approved for use in Europe are: 4-Methylbenzylidene camphor (4%); Bisoctrizole (10%);
`
`Bemotrizinol
`
`(10%); Bisdisulizole
`
`disodium (10%); Drometrizole
`
`trisiloxane
`
`(15%);
`
`Benzophenone-9 (10%); Ethylhexyl
`
`triazone (5%); Diethylamino hydroxybenzoyl hexyl
`
`10
`
`benzoate (10%); Iscotrizinol (10%); Polysilicone-15 (10%); and Isoamyl p-Methoxycinnamate
`
`(10%).
`
`Of these sunscreens, only Polysilicone-15 is a silicon based polymeric sunscreen with the
`
`IUPAC
`
`name
`
` a-(trimethylsilyl)-w-(trimethylsilyloxy)poly[oxy(dimethyl)silylene]-co-[oxy-
`
`(methyl)(2- {4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy}-1-methyleneethyl])silylene]-co-[oxy-
`
`15
`
`(methyl)(2-(4-[2,2-bis(ethoxycarbonyl)vinyl|phenoxy)prop-l-enyl)silylene] with
`
`about
`
`55
`
`oxy(dimethyl)silylene units, about 4 oxy(methyl)(2- {4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy}-
`
`l-methyleneethyl)
`
`silylene units
`
`and about
`
`1
`
`oxy(methyl)(2-(4-[2,2-bis(ethoxycarbonyl)
`
`vinyl|}phenoxy)prop-1-enyl)silylene units on average with an average molecular weight of 6,070.
`
`Statistically the random copolymer should have more than one percent of the chains that have no
`
`20
`
`UV absorbing chromophores. An equivalent polymer of about 1,000 molecular weight would
`
`have less than half of the chains containing any UV absorbing chromophores.
`
`Polymeric
`
`sunscreens have the potential to provide a simple mode of distribution of the sunscreen in a
`
`vehicle, and reduce or eliminate absorption of the sunscreen by the skin to whichit is applied.
`
`Many examples of polymeric sunscreens have been disclosed in the patentliterature.
`
`25
`
`US Patents 7,291,322, 6,376,679, 6,312,673, 6,251,373, 6,221,343, 6,214,324, 6,200,557,
`
`6,159,456,
`
`and
`
`5,753,209,
`
`and US
`
`Patent Application Publications
`
`2007/0020204,
`
`2004/0213746, 2002/0054860, and 2001/0026789 are directed to silicone based polymeric
`
`sunscreens that are random copolymers similar to Polysilicone-15 with various UV absorbing
`
`chromophores. Another form of polymeric sunscreens is random acrylic copolymers, as
`
`30
`
`disclosed in USPatents 5,741,924, 5,487,885, 5,099,027 and 4,524,061 (which also discloses the
`
`polymers from a cyclic lactams).
`
`Substantive polymers are prepared by random vinyl
`
`J:\UF\827P\Application.doc\srv
`
`

`

`3
`
`UF.827P
`
`copolymerization are disclosed in US Patent 7,087,692 and US Patent Application Publication
`
`2004/0101498 or by random condensation copolymerization, as disclosed in US Patents
`
`4,004,074 and 3,864,473. Water dispersible polymeric sunscreens have been prepared by a
`
`random condensation copolymerization with polyethylene glycol monomers, as disclosed in
`
`5,250,652, 5,243,021, and 5,134,223.
`
`An acrylamide homopolymer having UV active
`
`chromophores at every repeating unit
`
`is disclosed in US Patent 4,233,430. US Patent
`
`Application Publication 2005/0186152 discloses a polyanhydride modified by the addition of
`
`nucleophilic UV active chromophores to place the chromophores on every repeating unit of the
`
`polymer chain with the formation of an equal amount of carboxylic acid groups on the polymer
`
`10
`
`chain. US Patents 6,962,692, 6,926,887, 6,919,473, 6,899,866, 6,890,521, 6,800,274, and
`
`5,993,789, discloses a homo-polyester sunscreen where UV active chromophores are on every
`
`repeating unit of the polymer.
`
`As disclosed polymeric sunscreens have very high levels of UV absorbing chromophores
`
`that can result
`
`in a non-uniform distribution of the chromophores in the vehicles as in
`
`15
`
`homopolymer or with random copolymers where molecular weights or UV absorbing
`
`chromophores are limited to those where a high molecular weights or high levels of UV
`
`absorbing units. Hence a polymeric system where the UV absorbing chromophore’s distribution
`
`through out the polymer can be controlled with every polymer chain having the same proportion
`
`of UV absorbing chromophores independent of the molecular weight is attractive for a polymeric
`
`20
`
`sunscreen.
`
`BRIEF SUMMARY
`
`Embodiments of the invention are directed to poly(non-conjugated diene) based
`
`sunscreens where the polymer has a plurality of one or more repeating units where each
`
`25
`
`repeating unit has a chromophore unit having at least one UV absorbing chromophoresituated
`
`between two mono-ene units. The mono-ene units of the polymer are separated from the
`
`chromophore unit by chains.
`
`In embodiments of the invention the chains can be a plurality of
`
`methylene units. The UV absorbing chromophoresabsorbs light in the UVA and/or UVB region
`
`of the electromagnetic spectrum. The UV absorbing chromophores can be equivalents to and
`
`30
`
`derived from the conjugated group of the
`
`approved sunscreens: Aminobenzoic acid;
`
`Avobenzone; Cinoxate; Dioxybenzone; Homosalate; Menthyl anthranilate; Octocrylene; Octyl
`
`J\UF\827P\Application.doc\srv
`
`

`

`4
`
`UF.827P
`
`methoxycinnamate; Octyl salicylate; Oxybenzone; Padimate O; Phenylbenzimidazole sulfonic
`
`acid; Sulisobenzone; Trolamine salicylate; Ecamsule; Phenylbenzimidazole sulfonic acid; 4-
`
`Methylbenzylidene camphor; Bisoctrizole; Bemotrizinol; Bisdisulizole disodium; Drometrizole
`
`trisiloxane; Benzophenone-9; Ethylhexyl
`
`triazone; Diethylamino hydroxybenzoyl hexyl
`
`benzoate; Iscotrizinol; or Isoamyl p-Methoxycinnamate.
`
`The chromophore units can have
`
`bridging groups to connect the UV absorbing chromophores to the chromophore units.
`
`In
`
`embodiments of the invention, the bridging groups can include an alkylene group and a linking
`
`functionality that is a residue of an addition or a condensation reaction between functionality on
`
`the alkylene group and the UV absorbing chromophore.
`
`10
`
`Depending on the structures of the repeating units included in the poly(non-conjugated
`
`diene) based sunscreen,
`
`in some embodiments the UV absorbing chromophore can be
`
`periodically displaced along the backbone of the poly(non-conjugated diene).
`
`In other
`
`embodiments of the invention, the UV absorbing chromophore can be quasi-periodically or
`
`pseudo-randomly placed within the backbone of the poly(non-conjugated diene).
`
`In some
`
`15
`
`embodiments of the invention, one or more functionality to impart: substantive properties;
`
`dispersivity; and/or an ability to specifically interact with particles or chemicals can be
`
`incorporated into at least one repeating unit, or can be attached at one or both terminal mono-
`
`enes of the poly(non-conjugated diene).
`
`Other embodiments of the invention are directed to monomers for the preparation of the
`
`20
`
`above poly(non-conjugated diene) based sunscreens. The monomers have two terminal ene units
`
`connected by a chain to a chromophore unit that has one or more UV absorbing chromophores
`
`that
`
`independently absorb light
`
`in the UVA and/or UVB regions of the electromagnetic
`
`spectrum.
`
`In one embodiment of the invention,
`
`the chains between the ene units and
`
`chromophore units of the monomers are of equal length and composition, which allows the
`
`25
`
`formation of a periodic poly(non-conjugated diene). In another embodimentofthe invention, the
`
`chains can be ofdifferent lengths and compositions in the same monomerto permit formation of
`
`a quasi-periodic poly(non-conjugated diene). The monomers can include functionality that can
`
`impart substantive properties, dispersivity, and/or an ability to specifically interact with particles
`
`or chemicals.
`
`30
`
`Other embodiments of the invention are directed to a method of preparing a poly(non-
`
`conjugated diene) based sunscreens where one or more of the above monomers are polymerized
`
`J:\UF\827P\Application.doc\srv
`
`

`

`5
`
`UF.827P
`
`in the presence of a catalyst to promote acyclic olefin metathesis where ethylene is removed until
`
`a desired molecular weight is achieved. Olefin metathesis catalysts that can be use include
`
`Schrock’s catalyst or Grub’s catalyst.
`
`Other embodiments of the invention are directed to sunscreen drug products where the
`
`poly(non-conjugated diene) based sunscreens are included with a vehicle. The vehicle can
`
`include a solvent for the poly(non-conjugated diene) or can include a combination of a non-
`
`solvent and a dispersing agent to emulsify or suspend the poly(non-conjugated diene) in the non-
`
`solvent vehicle.
`
`Another embodiment of the invention is a method to prevent sunburn by providing a
`
`10
`
`poly(non-conjugated diene) based sunscreen which is applied to skin. The poly(non-conjugated
`
`diene) based sunscreen can be provided as a component of a fluid that is a solution or a
`
`dispersion.
`
`15
`
`BRIEF DESCRIPTION OF DRAWINGS
`
`Figures 1 shows a) a representation of current sunscreen technology and b) a polymer
`
`having a unit that acts as a sunscreen according to embodiments of the invention.
`
`Figure 2 showsthree poly(non-conjugated diene) based sunscreens with a UV absorbing
`
`chromophore on every ninth carbon along the backbone wherethe bridging groupis: a) an ester;
`
`20
`
`b) an amide; and c) an oligoether ester in accordance with embodiments of the invention.
`
`Figure 3 shows a monomerfor preparing a poly(non-conjugated diene) based sunscreen
`
`that has a chromophore unit that is a 5 to 10 carbon unit with two different UV absorbing
`
`chromophoresattached at the ends of the carbon by a spacer group.
`
`Figure 4 shows a specific monomer according to that illustrated in Figure 3 where the
`
`25
`
`UV absorbing chromophores are derived from Avobenzone and Octocrylene type of sunscreen
`
`components and connected to a 5 carbon chromophore unit where one bridging group is a
`
`methylene spacer with a carbonate functional group and the other bridging group is a methylene
`
`spacer with an ester functional group.
`
`Figure 5 shows the synthesis of a monomer and its polymerization to a poly(non-
`
`30
`
`conjugated diene) based sunscreen in accordance with embodiments of the invention.
`
`J:\UF\827P\Application.doc\srv
`
`

`

`6
`
`UF.827P
`
`DETAILED DISCLOSURE
`
`Embodiments of the invention are directed to poly(non-conjugated diene) based
`
`sunscreens that comprise polymers formed from a,w-diene monomers covalently attached to
`
`chromophore units comprising one or more UV absorbing chromophores. As illustrated in
`
`Figure 1, sunscreen molecules that are monomeric are often absorbable by the skin, which can
`
`allow radical/oxidative damage to the skin or can be toxic or carcinogenic to the sunscreen user.
`
`Asalso illustrated in Figure 1, the polymeric structure will, in general, prohibit the absorption of
`
`the individual UV absorbing chromophoresthat function as the sunscreen.
`
`In one embodiment
`
`10
`
`of the invention, a symmetric a,@-diene monomer can be polymerized via a step-growth acyclic
`
`diene metathesis (ADMET)self-condensation polymerization to yield polymers with a perfectly
`
`defined primary structure where UV absorbing chromophores are equally spaced in a periodic
`
`fashion along the polymer backbone.
`
`Three poly(non-conjugated diene) based sunscreens
`
`according to embodiments of the invention are illustrated in Figure 2. The monomer can be
`
`15
`
`designed to have a chain with one specific chain length between the ene groups and a
`
`chromophore unit containing at least one UV absorbing chromophore.
`
`In other embodiments of the invention, the UV absorbing chromophores can be separated
`
`from the enes by chains of two different lengths in a quasi periodic manner wherethere are only
`
`three different chain lengths between the UV absorbing chromophores. For example where a
`
`20
`
`monomer with 5 methylene units situated between one mono-ene and the UV absorbing
`
`chromophore and 10 methylene units situated between the other mono-ene and the UV absorbing
`
`chromophore is polymerized, chains of 12, 17, and 22 carbons between UV absorbing
`
`chromophores in the polymer occur in a 1:2:1 ratio but where chains of 12 or 22 carbons cannot
`
`be on adjacent sides of any given UV absorbing chromophore.
`
`In yet another embodiment of the
`
`25
`
`invention, a UV absorbing chromophores can be pseudo-randomly situated in a poly(non-
`
`conjugated diene) based sunscreen when two or more monomers are used where the chains
`
`between enes and UV absorbing chromophores have three or more values. These systems are
`
`only pseudo-random because every repeating unit of the resulting copolymer has only specific
`
`lengths of chains between UV absorbing chromophores defined by the monomerfeed ratio. For
`
`30
`
`example, in similar manner to the quasi-periodic polymer above, two monomers, one having 5
`
`methylene units between the UV absorbing chromophore and both mono-enes and another
`
`J\UF\827P\Application.doc\srv
`
`

`

`7
`
`UF.827P
`
`having 10 methylene units between the UV absorbing chromophore and both mono-ene units can
`
`be copolymerized in a one to one ratio to produces a polymer where chains of 12, 17, and 22
`
`carbons between UV absorbing chromophoresin a 1:2:1 ratio where chains of 12 or 22 carbons
`
`exist on adjacent sides of many UV absorbing chromophores of the copolymer.
`
`In some embodiments of the invention,
`
`the chains between the terminal enes of the
`
`monomersand their UV absorbing chromophore unit can consist exclusively of methylene units.
`
`In other embodiments of the invention the chains can comprise units that provide specific groups
`
`that provide specific functionality to the resulting polymers. For example, the chains can have
`
`units that provide groups for substantive properties to the skin, groups to promote dispersion in a
`
`10
`
`solvent, or groups to promote interaction with specific particles or chemicals in a sunscreen
`
`formulation. The structures of such groups are readily appreciated by those skilled in the art, and
`
`include, but are not exclusive to:
`
`tetra-alkyl ammonium salts, poly or oligo(ethyleneoxide)
`
`chains, or di or trialkoxysilane functionality. More than one UV absorbing chromophore can be
`
`attached to the monomer and two or more different UV absorbing chromophores can be included
`
`15
`
`in the monomer.
`
`For example, one chromophore that absorbs UVA radiation and one
`
`chromophorethat absorbs UVBradiation can be attached to the chromophore unit containing the
`
`UV absorbers.
`
`The invention employs o,w-diene monomers that can be homopolymerized by ADMET
`
`methods, yet, because the dienes
`
`are unreactive to a
`
`large proportion of chemical
`
`20
`
`transformations, a large variety of transformations can be carried out to attach the UV absorbing
`
`chromophores or other groups to impart other properties for the polymers from these monomers.
`
`Although, in principle, all of the novel polymers can be prepared alternately by the ring-opening
`
`metathesis polymerization of cyclic mono-enes, typically the lengths of the chains between the
`
`ene units in the polymers are larger than those that generally permit efficient preparation of
`
`25
`
`cyclic monoene monomers. By changing the number of methylene units between terminal
`
`mono-enes of the monomers and the chromophore unit, the resultant polymers can be loaded
`
`with different amounts of the UV absorbing chromophores. Where the repeating units are
`
`sufficiently large, the polymeric sunscreens can be oligomeric sunscreens as defined by the
`
`number of repeating units of the polymer, but can still be of sufficient molecular weight as to
`
`30
`
`possess the desirable properties of polymeric sunscreens, such as a lack of toxicity or
`
`J\UF\827P\Application.doc\srv
`
`

`

`8
`
`UF.827P
`
`carcinogenicity. Because ADMET polymerization can be carried out to any degree and stopped
`
`whenthe desired amount of ethylene is generated, any desired molecular weight can be achieved.
`
`In various embodiments of the invention, the molecular weight can be controlled by the
`
`inclusion of a mono-ene end-capper where the proportion of the diene monomers and the mono-
`
`enes can define the degree of polymerization of the resulting polymer in addition to the amount
`
`of ethylene released, or exclusively define the molecular weight for extremely high conversions
`
`of the terminal enes. The mono-enes can be compounds that have a group that provides
`
`substantive properties to the skin, groups to promote dispersion in a solvent or other vehicle, or
`
`promote interaction with specific particles or chemicals in a sunscreen formulation.
`
`The
`
`10
`
`structures of such groups are readily appreciated by those skilled in the art, and include, but are
`
`not exclusive to:
`
`tetraalkyl ammonium salts, poly or oligo(ethyleneoxide) chains, or di or
`
`trialkoxysilane functionality.
`
`The type of UV absorbing chromophores can be, but is not limited to those that have
`
`equivalent conjugated structures to those approved for use by the FDA or other worldwide
`
`15
`
`regulatory agencies.
`
`Those approved chromophores: Aminobenzoic acid; Avobenzone;
`
`Cinoxate;
`
`Dioxybenzone;
`
`Homosalate; Menthyl
`
`anthranilate;
`
`Octocrylene;
`
`Octyl
`
`methoxycinnamate; Octyl salicylate; Oxybenzone; Padimate O; Phenylbenzimidazole sulfonic
`
`acid; Sulisobenzone; Trolamine salicylate; Ecamsule; Phenylbenzimidazole sulfonic acid; 4-
`
`Methylbenzylidene camphor; Bisoctrizole; Bemotrizinol; Bisdisulizole disodium; Drometrizole
`
`20
`
`trisiloxane; Benzophenone-9; Ethylhexyl
`
`triazone; Diethylamino hydroxybenzoyl hexyl
`
`benzoate; Iscotrizinol; Isoamyl p-Methoxycinnamate; and those attached to Polysilicone-15.
`
`Other UV absorbing chromophores can be used including those equivalent to UV absorbing
`
`conjugated systems disclosed in: US Patents 7,291,322; 7,087,692; 6,962,692; 6,926,887;
`
`6,919,473; 6,899,866; 6,890,521; 6,800,274; 6,376,679; 6,312,673; 6,251,373; 6,221,343;
`
`25
`
`6,214,324; 6,200,557; 6,159,456; 5,993,789; 5,753,209; 5,741,924; 5,487,885; 5,250,652;
`
`5,243,021; 5,134,223; 5,099,027; 4,524,061; 4,233,430; 4,004,074; and 3,864,473 and US Patent
`
`Application Publications
`
`2007/0020204;
`
`2005/0186152;
`
`2004/0213746;
`
`2004/0101498;
`
`2002/0054860; and 2001/0026789. Many other conjugated systems that absorb in the UVA
`
`and/or UVB spectral ranges can be used, even somethat are known to be damagingto the skin or
`
`30
`
`to other organs or systems of an individual using a sunscreen, because the chromophoresis
`
`irreversibly bound to a polymer chain, rendering it passive to the system. The UV absorbing
`
`J:\UF\827P\Application.doc\srv
`
`

`

`9
`
`UF.827P
`
`chromophores can be linked in the chromophore unit by any sufficiently stable bridging group.
`
`For example, where the conjugated UV absorbing chromophore unit contains a carboxylic acid
`
`group, the chromophore unit can have a hydroxy group and the UV absorbing chromophores can
`
`be attached via ester functionality. One skilled in the art can readily appreciate appropriate
`
`complimentary functionalities to bridge the UV absorbing chromophores to chromophore unit of
`
`the monomers. Some embodiments of the invention are directed to preparation of monomers for
`
`the preparation of the novel poly(non-conjugated diene) based sunscreens where a UV absorbing
`
`chromophore comprising molecule is attached to a functional group of an a,@-diene molecule.
`
`The chromophore unit comprising the UV absorbing chromophore or chromophores can
`
`10
`
`include a coupling unit between a plurality of UV absorbing chromophores. For example, as
`
`illustrated in Figure 3, a chromophore unit can have a UVA absorbing chromophore and a UVB
`
`absorbing chromophoreattached at the ends of a 5 to 10 carbon linked chromophore unit by a
`
`spacer.
`
`Embodiments of the invention are directed to the formation of poly(non-conjugated
`
`15,
`
`diene) based sunscreens by the ADMET polymerization of a,@-diene monomers covalently
`
`attached to UV absorbing chromophores. Monomers, as described above, can be coupled by the
`
`use of any known metathesis catalyst, for example Schrock's catalyst Mo(=CHCMe>Ph)(N-2,6-
`
`C6H3-i-Pr2)(OCMe(CF3)2)2 or Grubbs’ catalyst RuClo(=CHPh)(PCy3)2. The formation of an a,-
`
`diene monomers and its polymerization to a poly(non-conjugated diene) based sunscreen is
`
`20
`
`illustrated by example in Figure 5 for a polymer formed having the UV absorbing chromophore
`
`derived from Avobenzone.
`
`In some embodiments of the invention, the poly(non-conjugated diene) based sunscreens
`
`can be further modified at the residual ene units of the polymer backbone. The ene units can be
`
`hydrogenated to methylene units or can undergo other addition reactions to form functional
`
`25
`
`groups that can be further elaborated into other groups. For example, water, ammonia, hydrogen
`
`sulphide, or HCl can be added across the ene units to form hydroxy, amine, thiol or chloride
`
`units with some regularity along the polymer backbone. The resulting units can be used to
`
`undergo condensation or addition reactions to form other functional groups. For example, a
`
`hydroxy unit can be used to add to ethylene oxide or other epoxy group or to condense with a
`
`30
`
`carboxylic acid ester or halide to functionalize the polymer. Someorall of the ene units can be
`
`J.\UF\827P\Application.doc\srv
`
`

`

`10
`
`UF.827P
`
`converted. Those skilled in the art can readily envision the scope of possible structures that can
`
`be generated from the ene units.
`
`All patents, patent applications, provisional applications, and publications referred to or
`
`cited herein are incorporated by reference in their entirety, including all figures and tables, to the
`
`extent they are not inconsistent with the explicit teachings of this specification.
`
`It should be understood that the examples and embodiments described herein are for
`
`illustrative purposes only and that various modifications or changes in light thereof will be
`
`suggested to persons skilled in the art and are to be included within the spirit and purview ofthis
`
`application.
`
`J:\UF\827P\Application.doc\srv
`
`