Ex Parte Richard

Patent Trial and Appeal BoardSep 25, 2012

11856237 (P.T.A.B. Sep. 25, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ROBERT E. RICHARD __________ Appeal 2011-005836 Application 11/856,237 Technology Center 1600 __________ Before TONI R. SCHEINER, ERIC GRIMES, and JEFFREY N. FREDMAN, Administrative Patent Judges. SCHEINER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52, directed to a polymeric particle. The claims have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. Appeal 2011-005836 Application 11/856,237 2 STATEMENT OF THE CASE Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 are pending and on appeal. Claim 1 is representative of the subject matter on appeal: 1. A particle, comprising: a material comprising a polymer backbone bonded to a chemical species via a 1,2,3-triazole group the particle has a maximum dimension of at most 5,000 microns. The Examiner relies on the following evidence: Lanphere et al. US 2004/0096662 A1 May 20, 2004 Hartmuth C. Kolb & K. Barry Sharpless, The growing impact of click chemistry on drug discovery, 24 DRUG DISCOVERY TODAY 1128-1137 (2003). Maisie J. Joralemon et al., Shell Click-Crosslinked (SCC) Nanoparticles: A New Methodology for Synthesis and Orthogonal Functionalization, 127 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 16892-16899 (2005). Dmitri A. Ossipov & Jöns Hilborn, Poly(vinyl alcohol)-Based Hydrogels Formed by “Click Chemistry”, 39 MACROMOLECULES 1709-1718 (2006). The claims stand rejected as follows: I. Claims 1, 3-5, 7, 10, 11, 13, 14, and 31 under 35 U.S.C. § 103(a) as unpatentable over Joralemon (Ans. 8-9). II. Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 under 35 U.S.C. §103(a) as unpatentable over Lanphere and Joralemon (Ans. 9-10). III. Claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 under 35 U.S.C. §103(a) as unpatentable over Lanphere and Ossipov (Ans. 4-6). IV. Claim 11 under 35 U.S.C. §103(a) as unpatentable over Lanphere, Ossipov, and Kolb (Ans. 6-7). Appeal 2011-005836 Application 11/856,237 3 PRINCIPLES OF LAW A rejection on the ground of obviousness must include “articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). “[T]his analysis should be made explicit” and it “can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does.” KSR Int’l Co., v. Teleflex Inc., 550 U.S. 398, 418 (2007). FINDINGS OF FACT 1. Joralemon discloses that “[c]lick chemistry between an alkynyl shell functionalized block copolymer micelle [i.e., a micelle formed from an amphiphilic diblock copolymer of poly(acrylic acid)80-b-poly(styrene)90] and an azido terminated dendrimer was employed to construct crosslinks between the polymer chain segments within the micelle corona, to yield shell Click-crosslinked (SCC) nanoparticles” (Joralemon Abstract; 16899, col. 1). The polymers in the resultant nanoparticles are cross-linked via 1,2,3-triazole groups, and have average diameters well below 5,000 microns, as shown in Table 1 below: (Joralemon 16897, Table 1.) Appeal 2011-005836 Application 11/856,237 4 2. Joralemon further teaches that “[t]his type of nanoparticle crosslinking and subsequent functionalization provides a facile route for the future attachment of biologically important molecules, therapeutics, and targeting ligands onto the nanoparticle” (Joralemon 16899, col. 2). 3. Lanphere discloses polymeric particles “having a diameter of about 500 microns or less . . . [with] a first density of pores in an interior region and a second [different] density of pores at a surface region” or “a first average pore size in an interior region and a second [different] average pore size at the surface region” (Lanphere ¶¶ 4, 5). For example, the density of pores in the center of the particle may be greater than the density of pores at the surface of the particle, or pores near the center of the particle may be relatively large, and pores near the surface may be relatively small (id. at ¶¶ 54, 62). According the Lanphere, this variation in pore size and/or density affects various properties of the particles, including compressibility and resistance to shear forces and abrasion (id. at ¶¶ 54, 55). 4. Lanphere‟s particles “are substantially formed of a polymer, such as . . . a high molecular weight polyvinyl alcohol (PVA) . . . [and] a minor amount . . . of a gelling material . . . such as [an] alginate” (Lanphere ¶ 53). Essentially, the base polymer and gelling material are combined, formed into droplets and solidified, and then the polymer in the solid drops is reacted with “an agent that chemically reacts with the base polymer to cause cross-linking between polymer chains and/or within a polymer chain” (id. at ¶¶ 84, 85). “For polyvinyl alcohol,” the cross-linking agent “includes one or more aldehydes, such as formaldehyde . . . and glutaraldehyde (id. at ¶ 85). Appeal 2011-005836 Application 11/856,237 5 5. According to Lanphere, the cross-linking agent “diffuses into the solid drops from the surface of the particle in a gradient which . . . provides more cross-linking near the surface of the solid drop than in the body and the center of the drop . . . providing a stiff, abrasion-resistant exterior” (Lanphere ¶ 85). 6. Ossipov teaches that “[c]hemically cross-linked PVA [poly(vinyl alcohol)] hydrogels have been mostly prepared using bifunctional cross-linking agents, such as glutaraldehyde . . . which react directly with PVAs hydroxyl groups” (Ossipov 1712, col. 1), but “cross- linking with low-molecular-weight toxic reagents is not practicable for in- situ hydrogel formation” (id.). 7. Ossipov discloses an alternative method, “which could afford in-vivo hydrogel formation” (Ossipov 1709, col. 1), in which hydrogels are prepared by “click chemistry” (id. at 1711, col. 2 (emphasis omitted)), i.e., by mixing “alkyne- and azide-modified PVAs . . . in the presence of Cu + catalyst” (id.). According to Ossipov, “chemoselective 1,3-cycloaddition between alkynyl and azido functional groups of PVA components . . . [resulted in] the multiple formation of triazole cross-links” (id. at 1712, col. 1; Figure 4A). 8. Ossipov teaches that the click-chemistry technique produces “solid, uniform hydrogels” (Ossipov 1718, col. 1). Ossipov does not disclose particles of any kind made from the PVA hydrogels. Appeal 2011-005836 Application 11/856,237 6 DISCUSSION I. Claims 1, 3-5, 7, 10, 11, 13, 14, and 31 stand rejected as unpatentable over Joralemon. The Examiner‟s position is that the claimed invention would have been obvious because Joralemon “teaches nanoparticles of poly(acrylic acid)-block-styrene that are cross-linked via 1,2,3-triazoles” (Ans. 8), and also suggests “[i]ncorporation of a drug, and attaching the drug to the nanoparticle, including covalent attachment to the 1,2,3-triazole” (id.). Appellant contends that Joralemon “teaches amphiphilic diblock copolymers of poly(acrylic acid)80-b-poly(styrene)90 that have been assembled into micelles . . . [which] flatten onto a mica surface „when drop deposited and allowed to dry freely in air . . . ‟” (App. Br. 6). Appellant contends that “[o]ne skilled in the art would have known that such a flattened micelle is not a particle” (Reply Br. 2). This argument is not persuasive. As discussed above, Joralemon explicitly describes the product of 1,2,3-triazole crosslinking between alkynyl shell functionalized block copolymer micelles and azido terminated dendrimers as SCC “nanoparticles” (FF1). The flattened shape of the nanoparticles is irrelevant, as the claims do not require spherical particles. The rejection of claims 1, 3-5, 7, 10, 11, 13, 14, and 31 as unpatentable over Joralemon is affirmed. II. Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 stand rejected as unpatentable over Lanphere and Joralemon. Appeal 2011-005836 Application 11/856,237 7 Again, the Examiner finds that Joralemon “teaches nanoparticles of poly(acrylic acid)-block-styrene that are cross-linked via 1,2,3-triazoles” (Ans. 8), and also suggests “[i]ncorporation of a drug, and attaching the drug to the nanoparticle, including covalent attachment to the 1,2,3-triazole” (id.). The Examiner further finds that Lanphere “teaches polyvinyl alcohol . . . particles cross-linked with formaldehyde . . . [with] diameters from 300- 500 microns” (id. at 4). The Examiner‟s position is that it would have been obvious to use a 1,2,3-triazole group to crosslink Lanphere‟s particles because Joralemon provides evidence that “1,2,3-triazole groups are known functionalities for crosslinking of nanoparticles used for drug delivery” (Ans. 10). Appellant contends that “the chemicals used by Joralemon to obtain his 1,2,5-triazole linkage are chemically incompatible with Lanphere‟s polyvinyl alcohol” (App. Br. 7). Appellant contends that “Joralemon‟s polymer contains polyacrylic acid, whose carboxylic acid group reacts with propargylamine to form a precursor product that subsequently reacts with 1- [3'-(dimethylamino)propyl]-3-ethylcarbodiimide methiodide to form the 1,2,3-triazole group when a copper sulfate catalyst is added” (id.). Appellant contends that “one skilled in the art would readily appreciate[] [that] Lanphere‟s polyvinyl alcohol (PVA) does not react with Joralemon‟s propargylamine to form the precursor product needed for formation of the 1,2,3-triazole group” (id.). Appellant‟s argument is persuasive with respect to dependent claim 15, the only claim on appeal actually limited to particles made of cross- linked polyvinyl alcohol backbones, and we will reverse the rejection with respect to this claim. Appeal 2011-005836 Application 11/856,237 8 However, Appellant‟s argument is not persuasive with respect to claims 1, 3-5, 7-11, 13, 14, 31, 45, 48, 49, and 52. As discussed above, Appellant‟s arguments with respect to Joralemon do not persuade us that claims 1, 3-5, 7, 10, 11, 13, 14, and 31 are patentable over Joralemon alone. Moreover, Appellant‟s arguments, whether in response to this rejection over Lanphere and Joralemon, or the previous rejection over Joralemon alone, are not relevant to the limitations of claims 8, 9, 45, 48, 49, and 52. The rejection of the claims as unpatentable over Lanphere and Joralemon is reversed with respect to claim 15, and affirmed with respect to claims 1, 3-5, 7-11, 13, 14, 31, 45, 48, 49, and 52. III. Claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 stand rejected as unpatentable over Lanphere and Ossipov. The Examiner finds that Lanphere “teaches polyvinyl alcohol . . . particles cross-linked with formaldehyde . . . [with] diameters from 300-500 microns” (Ans. 4). The Examiner finds that Lanphere‟s particles “may be porous” and that “Lanphere suggests the delivery of drugs . . . which may be in or on the particle[s]” (id.). The Examiner finds that Lanphere “does not teach cross-linking by a 1,2,3-triazole group” (id.). However, the Examiner finds that Ossipov “teaches cross-linked polyvinyl alcohol through a 1,2,3-triazole group” and also “teaches that the method . . . is advantageous over previously known methods of cross-linking PVA with toxic crosslinkers such as glutaraldehyde which is toxic and therefore unsuitable for in vivo crosslinking” (id. at 5). The Examiner concludes that it would have been obvious “to have used the cross-linking method of Ossipov to cross-link the PVA particle of Appeal 2011-005836 Application 11/856,237 9 Lanphere, thereby resulting in cross-links that contain the 1,2,3-triazole group structure” (id.), “instead of using an aldehyde for cross-linking as it eliminates the use of toxic substances” (id.). Appellant contends that “it would not have been obvious to modify Lanphere based on Ossipov” because Lanphere‟s objective was to produce an embolic particle with variable pore sizes in different regions of the particle, e.g., with small pores near the surface of the particle, to make the particle relatively stiff and incompressible, and enhance resistance to shear forces and abrasion (App. Br. 3-4), while “Ossipov‟s cross-linked product is described as a solid, uniform hydrogel” (id. at 4). Appellant‟s argument is persuasive. Lanphere uses an extrinsic cross- linker to diffuse into pre-gelled particles in order to form non-uniformly cross-linked particles with variable pore sizes and/or densities in different regions of the particles (FFs 3-5). Ossipov, on the other hand, forms a uniform hydrogel “by simply mixing . . . the prepared PVA components in the presence of Cu + catalyst” (Ossipov 1711, col. 2; FF7), and in any case, does not form particles at all (FF8). The Examiner has not explained how or why one of ordinary skill in the art would use Ossipov‟s click chemistry technique, in which functionalized polymers self-cross-link to form a solid, uniform structure, to form Lanphere‟s heterogeneous, non-uniformly cross- linked embolic particles. The rejection of claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 as unpatentable over Lanphere and Ossipov is reversed. Appeal 2011-005836 Application 11/856,237 10 IV. Claim 11 stands rejected as unpatentable over Lanphere, Ossipov, and Kolb. The Examiner relies on Lanphere and Ossipov as above, and cites Kolb as evidence that that “the covalent binding of drugs to the triazole reaction product of an azide and [an] alkyne” was known in the art (Ans. 6). As Kolb does not cure the underlying deficiency in the proposed combination of Lanphere and Ossipov, we will reverse this rejection as well. SUMMARY I. The rejection of claims 1, 3-5, 7, 10, 11, 13, 14, and 31 as unpatentable over Joralemon is affirmed. II. The rejection of claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 as unpatentable over Lanphere and Joralemon is reversed with respect to claim 15, and affirmed with respect to claims 1, 3-5, 7-11, 13, 14, 31, 45, 48, 49, and 52. III. The rejection of claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 as unpatentable over Lanphere and Ossipov is reversed. IV. The rejection of claim 11 as unpatentable over Lanphere, Ossipov, and Kolb is reversed. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED-IN-PART alw