Dirk Burdinski et al.Download PDFPatent Trials and Appeals BoardDec 3, 201913379056 - (D) (P.T.A.B. Dec. 3, 2019) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/379,056 12/19/2011 Dirk Burdinski 2009P00847WOUS 1013 24737 7590 12/03/2019 PHILIPS INTELLECTUAL PROPERTY & STANDARDS 465 Columbus Avenue Suite 340 Valhalla, NY 10595 EXAMINER PERREIRA, MELISSA JEAN ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 12/03/2019 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): katelyn.mulroy@philips.com marianne.fox@philips.com patti.demichele@Philips.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ________________ Ex parte DIRK BURDINSKI, JEROEN A. PIKKEMAAT, BERTRAND SCHMITT, HOLGER GRUELL, and SANDER LANGEREIS1 ________________ Appeal 2018-007312 Application 13/379,056 Technology Center 1600 ________________ Before JOHN G. NEW, SHERIDAN K. SNEDDEN, and RICHARD J. SMITH, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1We use the word “Appellant” to refer to the “applicant” as defined in 37 C.F.R. § 1.142. Appellant states the real party-in-interest is Koninklijke Philips Electronics N.V. App. Br. 3. Appeal 2018-007312 Application 13/379,056 2 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1, 3–7, and 9–17. Specifically, claims 1, 3–7, and 9–17 stand rejected as unpatentable under U.S.C. § 103(a) as being obvious over the combination of Kirpotin et al. (US 5,411,730, May 2, 1995) (“Kirpotin”), Briel et al. (US 2007/0014730 A1, January 18, 2007) (“Briel”), P. Reimer et al., Ferucarbotran (Resovist): A New Clinically Approved RES-Specific Contrast Agent for Contrast-Enhanced MRI of the Liver: Properties, Clinical Development, and Applications, 13 EUR. RADIOL. 1266–76 (2003) (“Reimer”), G. Bottoni, Size Effect on the Time Dependence of Magnetization of Iron Oxide Particles, 33 IEEE TRANS. MAG. 3049–51 (1997) (“Bottoni”), Markov et al. (WO 2008/0099346 A1, August 21, 2008) (“Markov”), and Viglianti et al. (US 7,672,704 B2, March 2, 2010) (“Viglianti”). Claims 1, 3–7, and 9–17 also stand rejected as unpatentable under U.S.C. § 103(a) as being obvious over the combination of Briel, Reimer, Kirpotin, Bottoni, Markov, Viglianti, Fisher et al. (US 7,947,307 B2, May 24, 2011) (“Fisher”), and S. Hashimoto et al., The Measurement of Small Magnetic Signals from Magnetic Nanoparticles Attached to the Cell Surface and Surrounding Living Cells Using a General-Purpose SQUID Magnetometer, 54 PHYS. MED. BIOL. 2571–83 (2009) (“Hashimoto”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. Appeal 2018-007312 Application 13/379,056 3 NATURE OF THE CLAIMED INVENTION Appellant’s invention is directed to a composition comprising a shell structure forming a cavity, wherein said shell structure comprises a drug and wherein said composition is associated with at least one contrast agent. Abstr. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A composition comprising a shell structure forming a cavity, wherein said shell structure comprises a drug and wherein said composition is associated with at least one contrast agent; wherein said shell structure is capable of releasing its contents into the exterior upon the application of an external stimulus and wherein said contrast agent comprises magnetic particles composed of Fe, Co, Ni, Zn or Mn or alloys thereof or oxides of any of these, preferably composed of Fe2O3 or Fe3O4, which are capable of being detected by Magnetic Particle Imaging (MPI), wherein at least more than 5% (w/w) of the magnetic particles comprised in said contrast agent have a magnetic moment of at least 10-18 m2A and wherein at least more than 5% (w/w) of said magnetic particles have a remagnetization time of less than l0 milliseconds per particle and wherein at least more than 5% (w/w) of said magnetic particles have a size of about 5nm to 50nm, wherein the composition includes a distribution of magnetic particles that balances between size, remagnetization time and magnetic moment to support MPI. App. Br. 22. ISSUES AND ANALYSES We agree with, and adopt, the Examiner’s findings and conclusion that the appealed claims are obvious over the combined cited prior art references. We address the arguments raised on appeal by Appellant below. Appeal 2018-007312 Application 13/379,056 4 A. Rejection of the claims over Briel, Reimer, Kirpotin, Bottoni, Markov, and Viglianti 1. Claims 1, 3–6, and 13–16 Issue 1 Appellant argues the Examiner erred in finding the combined cited prior art references teach or suggest the limitation of claim 1 reciting: “wherein at least more than 5% (w/w) of said magnetic particles have a remagnetization time of less than 10 milliseconds per particle.” App. Br. 8. Analysis The Examiner finds that Kirpotin teaches superparamagnetic iron oxide particles having an effective hydrodynamic diameter in the range of 5– 50 nm. Final Act. 3. The Examiner finds that Kirpotin teaches particles displaying a magnetic moment greater than 10–15 erg/Gauss, which the Examiner finds encompasses the claimed 10-18 Am2). Id. The Examiner finds that Briel teaches polycrystalline magnetic iron oxide particles (Resovist) in a pharmaceutically acceptable shell (e.g., dextran) and the use of these compositions in magnetic particle imaging (“MPI”). Final Act. 3–4. The Examiner finds that Briel teaches that Resovist comprises SPIO microparticles (magnetite-Fe3O4/Maghemite- Fe2O3) coated with carboxydextran, as further evidenced by Reimer. Id. at 4. The Examiner finds that Appellant’s Specification teaches that the magnetic particles of the instant claims include Resovist. Final Act. 4 (citing Spec. 31, ll. 2–6). Therefore, the Examiner finds, the 5–50 nm Appeal 2018-007312 Application 13/379,056 5 dextran-coated iron oxide particles of Kirpotin encompass the Resovist of the instant claims and have the same properties and are capable of the same functions, such as at least more than 5% of the dextran-coated particles having a size about 5 nm to 50 nm. Id. The Examiner further finds that Bottoni teaches generally that the variation of the magnetization in the time of the samples, in a magnetic field, occurs with decreasing size of the particles, and that it would therefore have been predictable to examine the magnetization of iron oxide particles of different sizes. Final Act. 4. Finally, the Examiner finds that Markov teaches that MPI requires high-performance tracer materials (e.g., Resovist) that are highly magnetic monodispersed particles with fast remagnetization behavior. Final Act. 4. The Examiner therefore concludes that, at the time of Appellant’s invention, it would have been obvious to a person of ordinarily skill in the art that the remagnetization time of the iron oxide particles is less than 10 milliseconds per particle. Final Act. 4. The Examiner arrives at this conclusion because Markov teaches that Resovist is a highly magnetic monodispersed particles with fast remagnetization behavior and because Bottoni teaches that the variation of the magnetization in the time of the samples occurs with decreasing size of the particles. Id. Appellant argues that neither Markov nor Bottoni teach or suggest the limitation of claim 1 reciting: “wherein at least more than 5% (w/w) of said magnetic particles have a remagnetization time of less than l0 milliseconds per particle.” App. Br. 9. Appellant contends that, even assuming, arguendo, that Markov teaches that Resovist is a highly magnetic monodispersed particle with fast remagnetization behavior and that Bottoni Appeal 2018-007312 Application 13/379,056 6 teaches that the variation of the magnetization in the time of the samples occurs with decreasing size of the particles, the combined teachings of Markov and Bottoni still do not explicitly or implicitly disclose magnetic particles having the specific remagnetization time of less than 10 milliseconds. Id. at 10. Instead, argues Appellant, both Markov and Bottoni are silent with respect to the recited magnetization time of less than 10 milliseconds. Id. Therefore, Appellant asserts, a person of ordinary skill in the art would have had no suggestion from the cited references to provide a contrast agent having magnetic particles with a specific remagnetization time of less than 10 milliseconds per particle. Id. Furthermore, argues Appellant, a skilled artisan would have no motivation to combine the teachings of Markov and Bottoni. App. Br. 10. According to Appellant, Markov concerns magnetic particle separation for MPI, whereas Bottoni concerns the thermal stability of magnetic particles in a recording medium. Id. Appellant specifically notes that Bottoni does not involve the remagnetization activity of a contrast agent, but rather teaches the magnetic decay of a recording media in the presence of reverse field. Id. Appellant argues that the teachings of Bottoni with respect to magnetization decay in the presence of a reverse field to determine thermal stability of the magnetic particle does not pertain in any way to remagnetization or the duration of particle remagnetization time. Id. Appellant further argues that Bottoni also does not disclose that the magnetization differences affect properties of the magnetic particles for a contrast agent. Id. Appellant contends that the Examiner has failed to provide any reasonable basis for a person with ordinary skill in the art to have combined the references. Id. Appeal 2018-007312 Application 13/379,056 7 Finally, Appellant notes that the Examiner relies upon Reimer as teaching that Resovist comprises superparamagnetic iron oxide (“SPIO”) microparticles coated with carboxydextran. App. Br. 12 (citing Final Act. 4) We are not persuaded by Appellant’s argument. Both Markov and Reimer teach Resovist as suitable for use in MPI and MRI, including possessing “fast remagnetization time.” See Bottoni Abstr.; Markov Abstr., col. 7, ll. 23–27. Appellant’s Specification expressly discloses Resovist as a SPIO suitable for the purposes of the claimed invention. Specifically, Appellant’s Specification discloses that: Particularly preferred is a combination of MPI and MRI as mentioned herein above, wherein MPI may preferably be used upon the induction of a release from the composition to determine the absolute local particle concentration at a certain site and wherein MRI may preferably be used to visualize the drug release event as such. This approach may be carried out with only one type of contrast agent, which is capable of being detected by MPI and by MRI, e.g. a contrast agent comprising magnetic particles of different sizes or different magnetic moments or remagnetization times such as Resovist, or by combining typical MPI contrast agents and typical MRI contrast agents as defined herein above. Spec. 30–31 (emphasis added). This disclosure is directly reflected in independent claim 1’s recitation of “wherein the composition includes a distribution of magnetic particles that balances between size, remagnetization time and magnetic moment to support MPI.” We agree with the Examiner that a person of ordinary skill would understand from the teachings of Reimer and Markov, and from the disclosure of Appellant’s Specification, that Resovist, which was well known in the prior art, must necessarily, and thus inherently, possess the Appeal 2018-007312 Application 13/379,056 8 claimed properties recited in claim 1 of “a distribution of magnetic particles that balances between size, remagnetization time and magnetic moment to support MPI,” in which “at least more than 5% (w/w) of said magnetic particles have a remagnetization time of less than l0 milliseconds per particle” See Final Act. 4. With respect to Appellant’s argument that a skilled artisan would have had no reason to combine Bottoni and Markov because the references are, impliedly, nonanalogous art, we are similarly not persuaded. Appellant’s claims recite magnetic particles, preferable composed of iron oxides (i.e., Fe2O3 or Fe3O4). Bottoni is directed to determining the dependence of the thermal stability of the magnetization on the size of iron oxide particles, by measuring the variation of the magnetization in presence of a reverse field. Bottoni Abstr. Bottoni teaches that “when the size of the particles decreases, the thermal stability of the magnetization is progressively weakened, with increase of magnetization decay, magnetic viscosity and fluctuation field and decrease of activation volume.” Id. The Examiner relies upon Bottoni’s teaching that the stability of magnetization is a function of particle size, which would have been a factor in selecting the claimed size range of iron oxide particles. See Final Act. 4. Markov teaches that MPI requires high-performing tracer materials that are highly magnetic monodispersed particles with fast remagnetization behavior. Markov Abstr. Specifically, Markov teaches that: “It is therefore an object of the present invention to provide a method such that improved magnetic particles result [i.e., with the requisite fast magnetization times], especially for an application in magnetic particle imaging.” Markov teaches that: “It is anticipated that, in a particular particle assay, there is a Appeal 2018-007312 Application 13/379,056 9 relationship between magnetic anisotropy and magnetic moment. In a mixture of poly-grain iron[ ]oxide particles, e.g.[,] Resovist, particle magnetic anisotropy will be set by a combination of shape and intrinsic anisotropy.” Id. at col. 7, ll. 23–27. Therefore, both Bottoni and Markov are related to the magnetic stability, and the related remagnetization time of iron oxide particles, including, in the case of Markov, Resovist. “Two separate tests define the scope of analogous prior art: (1) whether the art is from the same field of endeavor, regardless of the problem addressed and, (2) if the reference is not within the field of the inventor's endeavor, whether the reference still is reasonably pertinent to the particular problem with which the inventor is involved.” In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004). Whereas it is true that Bottoni is silent with respect to MPI, both references are directed to the magnetic properties, including remagentization time, of iron oxide particles, which are recited in Appellant’s claims and are certainly pertinent to the problem with which the inventor is concerned. Appellant’s argument that a skilled artisan would not combine the references because they are nonanalogous art is, consequently, not persuasive. Issue 2 Appellant argues that the combined cited references neither teach nor suggest the limitation of claim 1 reciting: “a shell structure forming a cavity, wherein said shell structure comprises a drug and wherein said composition is associated with at least one contrast agent compris[ing] metal particles,” in which “the composition includes a distribution of magnetic particles that Appeal 2018-007312 Application 13/379,056 10 balances between size, remagnetization time and magnetic moment to support MPI.” App. Br. 12. Analysis Appellant argues that Kirpotin, Briel, Viglianti, Needham, and Reimer, taken either singly or in combination, fail to teach or suggest at least a composition which includes “a shell structure forming a cavity, wherein said shell structure comprises a drug and wherein said composition is associated with at least one contrast agent compris[ing] metal particles,” in which “the composition includes a distribution of magnetic particles that balances between size, remagnetization time and magnetic moment to support MPI” as recited in independent claim 1. App. Br. 12. According to Appellant, there is no teaching or suggestion in any of these references that the magnetic particles may be distributed specifically to balance between size, remagnetization time and magnetic moment to support MPI. Id. at 13. Instead, argues Appellant, these references are silent with respect to balancing a distribution of magnetic particles with respect to size, remagnetization time and magnetic moment. Id. Appellant asserts that the Examiner has failed to sufficiently explain how the cited references teach these specific features, and has therefore failed to establish a prima facie case of obviousness with respect to these features. Id. We disagree. Both Markov and Reimer teach Resovist, which comprises SPIOs suitable for MPI as prior art to Appellant’s claimed invention. As we have explained, Appellant’s Specification discloses that Resovist is “a contrast agent comprising magnetic particles of different sizes or different magnetic moments or remagnetization times.” Spec. 31. We Appeal 2018-007312 Application 13/379,056 11 therefore agree with the Examiner that a skilled artisan would have known that Resovist which was known at the time of invention, inherently possessed the recited qualities. We consequently affirm the Examiner’s rejection of claims 1, 3–6, and 13–16. 2 Claims 7, 9–12, and 17 Issue Appellant argues that the Examiner erred because the combined cited prior art neither teaches nor suggests “administering a composition that is a carrier for a controlled delivery of a drug” which has a “shell structure [that] is capable of releasing its contents including the drug into the exterior upon the application of an external stimulus” and “imaging the composition by MPI to provide quantitative information concerning a release of the drug and modifying the application of an external stimulus for releasing a drug from a carrier based upon quantitative information concerning the release of the drug acquired by MPI imaging.” App. Br. 14. Analysis Appellant relies upon the same arguments presented supra with respect to claims 1, 36, and 13–16. App. Br. 13. Appellant argues further that the cited prior art neither teaches nor suggests a method which includes the features of modifying the application of an external stimulus for releasing a drug from a carrier based upon quantitative information concerning the release of the drug acquired by MPI imaging. App. Br. 14. Appellant argues that the Examiner relies upon Viglianti as teaching these features. App. Br. 14. According to Appellant, Viglianti teaches that Appeal 2018-007312 Application 13/379,056 12 the accumulation of the compound of interest may be monitored by magnetic resonance imaging. Id. Appellant contends that Viglianti teaches only that treatment variables may be modified to improve the uniformity of drug delivery based on monitoring of tissue drug concentration distribution. Id. (citing Viglianti col. 18, ll. 31–37). However, Appellant argues, Viglianti does not teach or suggest that an external stimulus for releasing a drug from the carrier may be modified based upon quantitative information concerning the drug release obtained by MRI imaging. Id. Nor, Appellant argues, does Kirpotin, upon which the Examiner relies, teach the disputed limitation. App. Br. 15. Appellant contends that Kirpotin teaches only that liposomes that encapsulate particles may transport chemotherapeutic drugs, and that the release of the drugs may be induced by localized heating. Id. (citing, e.g., Kirpotin cols. 4–5, ll. 55–13). However, Appellant asserts, Kirpotin is silent with respect to modifying the application of the external stimulus, such as the localized heating taught by Kirpotin, based on imaging which provides quantitative information concerning the release of the drug. Id. The Examiner responds that Kirpotin teaches that its ferroliposomes can be induced to release chemotherapeutic agents by “melting” of the liposome structure at a tumor site via localized heating induced by application of an oscillating electromagnetic field (i.e., an external stimulus). The Examiner finds that the proper choice of liposome transition temperature allows for the release of the therapeutic agent at the desired time and place via localized heating. Ans. 19. Appeal 2018-007312 Application 13/379,056 13 The Examiner finds that Viglianti teaches an in vivo method of monitoring the localization and distribution of a compound of interest to a desired site in an organism by magnetic resonance imaging. Ans. 19. The Examiner concludes that it would have been obvious to a person of ordinary skill in the art to monitor the distribution of a compound of interest to a desired site (e.g., drug delivery/data acquisition for the control of a drug delivery process) in an organism by MPI with the ferroliposomes. Ans. 19. The Examiner arrives at this conclusion because both references are directed to the release of drugs, contrast agents, etc., from an envirosensitive liposome to a desired site for the treatment and/or diagnosis of a disease, and because Viglianti further teaches the advantage of real-time monitoring of drug delivery and allows for monitoring of liposomal drug delivery in individual patients, leading to individualized treatment that can increase overall efficacy which encompasses determining the treatability of a disease condition in a patient, and/or improving treatment of a patient. Id. We agree with the Examiner. Kirpotin teaches that: [M]agnetic particles prepared according to the invention and encapsulated in liposomes can have an extended lifetime in the bloodstream. Such particles largely escape the RES clearance which is the usual fate of injected magnetic particles. Such liposome encapsulated particles are termed ferroliposomes herein. In addition to acting as carriers for magnetic particles, the liposomes serve as vehicles for transport of incorporated therapeutic agents such as chemotherapeutic drugs. By proper choice of liposome transition temperature, the therapeutic agent can be released at the desired time and place by localized heating induced by application of an oscillating electromagnetic field. Kirpotin col. 4, ll. 55–68. Viglianti teaches: Appeal 2018-007312 Application 13/379,056 14 [M]ethods and compositions … generally relat[ing] to employing magnetic resonance techniques to monitor drug delivery in vivo. More particularly, the disclosure relates to the use of liposomes encapsulating a drug and a contrast agent to monitor drug delivery to a desired site in vivo by magnetic resonance imaging techniques. Specifically, Viglianti teaches that: Yet another advantage of the present methods and compositions is the ability to perform real time monitoring of events occurring in vivo. A researcher can monitor, for example, the accumulation of liposome compositions at a heated site as the accumulation is occurring. The only delay is that delay associated with obtaining (for example, about 0.5–4 minutes, depending on scan settings) and processing (for example, less than about 3–6 seconds) the nucleus relaxation times to 40 images. This ability can be of great benefit in determining the time scale upon which events are occurring. This can translate into an estimate of the efficiency with which a given compound of interest is not only delivered to a site of interest, but also how the compound behaves once it has been delivered. Id. at col. 16, ll. 3–46. Viglianti further teaches that: A Site Can be Heated by Invasive/Noninvasive Techniques In one aspect of the present disclosure, a site of interest is heated. Heating of the site of interest leads to the accumulation of liposome composition at the heated site over a period of time (FIGS. 2A-2B). Without heating the site of interest, the liposome might at best diffusely accumulate at the site (particularly if it is a tumor) for a brief time (FIG. 2E), or not at all (FIG. 2D). The site can be heated by invasive or noninvasive methods and can depend on the nature of the site being heated. Id. at ll. 47–57. We agree with the Examiner that a person of ordinary skill in the art would have understood that the combined teachings of Viglianti, Kirpotin, Appeal 2018-007312 Application 13/379,056 15 and the other cited references teach using the magnetic particles as an quantitative indicator of the concentration of ferroliposomes at a target site, via MPI, to provide quantitative information concerning a release of the drug, and modifying the application of an external stimulus, i.e., "selecting a liposome transition temperature, for releasing a drug from a carrier based upon quantitative information concerning the release of the drug acquired by MPI imaging. We consequently affirm the Examiner’s rejection of claims 7, 9–12, and 17. B. Rejection of the claims over Briel, Reimer, Kirpotin, Bottoni, Markov, Viglianti, Fisher and Hashimoto Appellant argues that Fisher and Hashimoto fail to claim the alleged deficiencies of the remaining references, as argued supra. App. Br. 17–20. We have explained why we affirm the Examiner’s rejection over Briel, Reimer, Kirpotin, Bottoni, Markov, and Viglianti, and we incorporate that reasoning by reference here. We consequently affirm the Examiner’s rejection of the claims. DECISION The Examiner’s rejection of claims 1, 3–7, and 9–15 as unpatentable under 35 U.S.C. §103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R. § 1.136(a)(1)(iv). Appeal 2018-007312 Application 13/379,056 16 AFFIRMED Claims Rejected 35 U.S.C. § Basis Affirmed Reversed 1, 3–7, 9–15 103(a) Kirpotin, Briel, Reimer, Bottoni, Markov, Viglianti 1, 3–7, 9–15 1, 3–7, 9–15 103(a) Kirpotin, Briel, Reimer, Bottoni, Markov, Viglianti, Fisher, Hashimoto 1, 3–7, 9–15 Overall Outcome 1, 3–7, 9–15 Copy with citationCopy as parenthetical citation