YEH, James Shue-MinDownload PDFPatent Trials and Appeals BoardDec 13, 20212021002061 (P.T.A.B. Dec. 13, 2021) 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. 14/654,650 06/22/2015 James Shue-Min YEH 1380-6PUS (P528775US-PCT) 5448 31292 7590 12/13/2021 CHRISTOPHER & WEISBERG, P.A. 1232 N. University Drive Plantation, FL 33322 EXAMINER PERREIRA, MELISSA JEAN ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 12/13/2021 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): docketing@cpaglobal.com ptomail@cwiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAMES SHUE-MIN YEH Appeal 2021-002061 Application 14/654,650 Technology Center 1600 BEFORE ERIC B. GRIMES, JEFFREY N. FREDMAN, and JOHN E. SCHNEIDER, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70.2 We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies the real party in interest as the inventor, James Shue-Min Yeh. Appeal Br. 3. 2 Claims 65–69 and 71–75 are pending in the application but have been withdrawn from consideration. Final Act. 1. Appeal 2021-002061 Application 14/654,650 2 CLAIMED SUBJECT MATTER The claims are directed to ultrasound molecular imaging. Ultrasound molecular imaging “facilitates imaging of a given molecular moiety/moieties of interest (expressions) by way of targeting microbubbles, which comprise targeting ligands (molecular binding elements) on the particle shell.” Spec. 1. The invention is directed to microparticles suitable for use in ultrasound molecular imaging. Id. at 2. Claim 1, reproduced below, is illustrative of the claimed subject matter: 1. A microparticle composition suitable for molecular imaging, the composition comprising microparticles, wherein the microparticles comprise: a core microparticle structure having a central area and a shell, and wherein the core microparticle structure comprises: (i) a C18-24 saturated phosphatidylcholine lipid in a molar ratio of 72 to 78; (ii) a C18-24 saturated phosphatidylethanolamine lipid comprising at least one maleimide moiety in a molar ratio of 7 to 12 and a polyethylene glycol chain with a molecular weight of at least 500; and (iii) an alkoxylated fatty acid in a molar ratio of 12 to 18, the alkoxylated fatty acid being a C18-24 saturated polyethylene glycol fatty acid ester. REFERENCES The prior art relied upon by the Examiner is: Name Reference Date Unger US 6,088,613 July 11, 2000 Rychak US 2012/0244078 Sept. 17, 2012 Appeal 2021-002061 Application 14/654,650 3 REJECTION The Examiner has rejected claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70 under 35 U.S.C. § 103 as unpatentable over Rychak in view of Unger. OPINION Issue The issue before us is whether a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70 would have been obvious to one of ordinary skill in the art at the time the invention was made over Rychak combined with Under. The Examiner finds Rychak teaches “a gas-encapsulated injectable microbubble bearing a targeting ligand specific for a molecular target on its surface.” Ans. 3. The Examiner finds the microbubble of Rychak comprises a shell comprising a first surfactant which may be phosphatidyl choline which has a mole ratio of 5–90% relative to the other shell components Id. at 4. The Examiner finds that shell of Rychak also comprises a second surfactant which may be disteroylphosphatidylethanolamine-polyethylene glycol-2-pyridyl sulfide (“DSPE-PEG(2000)-PDP”) which is present in the shell in a moles/moles ratio of 0.1-99%, relative to other shell components. Id. The Examiner finds that the microbubble comprises a targeting ligand immobilized in the shell. Id. at 5. The Examiner finds the targeting ligand of Rychak is present in the shell in a mole ratio of from 0.1 to 5% relative to the other components of the shell. Id. The Examiner find the ligand can be a peptide, a protein or an antibody. Id. Appeal 2021-002061 Application 14/654,650 4 The Examiner finds Rychak does not teach the specific mole ratios recited in the claims but finds these mole ratios are suggested by Unger. Id. at 6–7. The Examiner concludes: At the time of the invention it would have been obvious to one ordinarily skilled in the art to vary and/or optimize the amount of the lipids, labelling moiety, molecular binding element etc., provided in the composition, according to the guidance provided by Rychak, to provide a composition having the desired properties such as the desired ratios as Rychak teaches of that the first surfactant is present in the shell in a moles/moles ratio of 5-90%, relative to other shell components, the second surfactant is present in the shell in a moles/moles ratio of 0.1-99%, relative to other shell components, the targeting ligand is present in the shell in a moles/moles ratio of 0.1-5%, relative to other shell components and the optically active probe is present in the shell in a moles/moles ratio of 0.1- 10%, relative to other shell components. Also, Unger teaches of gas filled microbubbles comprising 77.5 mole percent DPPC, 12.5 mole percent DPPA and 10 mole percent DPPE/PEG5000 or 82/10/8 ratio of mole percentages. Therefore, it would have been predictable to look to Unger for guidance for the mole% ratios of the microbubble lipid constituents. For example, one would examine the phosphatidylcholine in a range between about 77.5 to 82 mole%, and phosphatidylethanolamine lipid in a range between about 8-10 mole%. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955). Id. at 7–8. Appellant contends that Unger only discloses hypothetical examples and uses a negatively charged lipid which is not an element of the present claims. Appeal Br. 5–6. Appellant argues the examples of Rychak do not Appeal 2021-002061 Application 14/654,650 5 teach the claimed invention as the length of the phosphatidylcholine lipid in example 2 is not disclosed and Example 1 does not disclose the third component of the claims. Id. at 7. Appellant also contends that Rychak does not teach the specific mole ranges recited in the claims. Id. Appellant contends that the microparticles of Rychak and Unger are designed for different purposes and that one skilled in the art would not combine the teachings of the references. Id. at 7–9. Appellant contends that the microparticles of Rychak are designed to be fragile so that they can be easily degraded by acoustic action, whereas the microparticle of Unger are designed to be stable. Id. Appellant contends that combining the teachings of the references would result in a particle that is unsatisfactory for its intended purpose. Id. Appellant also contends that Unger incorporates a charged lipid into the shell to increase vesicle stability and that this would be contrary to the purpose of Rychak which is to have a vesicle that is easily disrupted. Id. at 9–10. Appellant contends that there is no motivation to combine the teachings of the references. Id. Appellant contends that one skilled in the art would not apply the mole ratios taught in Unger to the composition of Rychak. Id. at 11–13 and 15–18. Appellant contends that Unger teaches charged lipids that comprise fewer carbon atoms and that this would lead one skilled in the art way from using the mole ratios of Unger in Rychak. Id. Appellant contends that Unger fails to teach binding the negatively charged lipid to a PEG group. Id. at 13–14. Appellant contends that Rychak does not teach a C18-24 phosphatidylcholine lipid as Example 2, which teaches a microbubble comprising 40 mg of phosphatidylcholine, 20 mg polyoxyethylene 40 Appeal 2021-002061 Application 14/654,650 6 stearate, and 5 mg of PDP-PEG(2000)disteroylphosphatidylethanolamine does not disclose the chain length of the phosphatidylcholine. Id. at 19. Appellant contends that the rejection is based on the improper use of hindsight. Id. at 20. Appellant contends that only through the use of hindsight would one have been lead to the claimed composition. Id. Finally, Appellant contends that the claimed invention possesses unexpected advantages not taught or suggested by Rychak or Unger. Id. at 21–25. Legal Principles [T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant. After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). The test of obviousness is “whether the teachings of the prior art, taken as a whole, would have made obvious the claimed invention.” In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). “[W]here there is a range disclosed in the prior art, and the claimed invention falls within that range, there is a presumption of obviousness. But the presumption will be rebutted if it can be shown: (1) That the prior art Appeal 2021-002061 Application 14/654,650 7 taught away from the claimed invention, In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997); or (2) that there are new and unexpected results relative to the prior art, In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990).” Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004). Analysis We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions set out in the Final Action and Answer regarding this rejection. We find the Examiner has established a prima facie showing that the subject matter of the claims would have been obvious over Rychak combined with Unger to a person of ordinary skill in the art at the time the invention was made. Appellant has not produced evidence showing, or persuasively argued, that the Examiner’s determinations on obviousness are incorrect. Only those arguments made by Appellant in the Briefs have been considered in this Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv). We have identified claim 1 as representative; therefore, all claims fall with claim 1. We address Appellant’s arguments below. Appellant contends that Unger does not contain any data to show that any of the lipids disclosed therein would actually work as described and that Unger’s examples are prophetic. Appeal Br. 4–6. Appellant contends that this supports its contention that the rejection is in error. Id. We are not persuaded by this argument. Unger was relied on only for the teaching of the relative mole ratios of the different components recited in the claims. See Ans. 6–7. Appellant has offered no evidence to show why one skilled in the art would not accept this teaching at face value. “[A]ll disclosures of the prior art . . . must be considered.” In re Lamberti, 545 F.2d 747, 750 (CCPA1976). In addition, as discussed below, the recited Appeal 2021-002061 Application 14/654,650 8 ranges fall within the ranges taught by Rychak, supporting a prima facie case of obviousness. Appellant contends that Rychak fails to teach the claimed composition in that Example 2 does not disclose the length of the phosphatidylcholine used. Appeal Br. 7. Appellant contends that while Example 1 of Rychak discloses a C18 phosphatidylcholine, the composition recited in that example is missing the third element of the claims. Id. This argument is unpersuasive. Rychak teaches that the first lipid can be a phospholipid having an acyl chain of from 10 to 28 carbon atoms and lists phosphatidylcholine as an example. Rychak, claims 1–5. As Appellant points out, Example 1 of Rychak teaches the use of a C18 phosphatidylcholine. Id. ¶ 49. We find that, given the teachings of Rychak as a whole, it would have been obvious to one skilled in the art reading Rychak to use a C18 phosphatidylcholine to make the microbubbles of Rychak. Appellant contends that Rychak does not teach or suggest the ranges of mole ratios recited in the claims. Appeal Br. 7. Appellant contends that the ranges recited in Rychak are so broad “as to encompass practically any quantity of these components, and consequently provide no teaching of an actual amount or moles/moles ratio of these components that can be used in a microbubble composition.” Again, this argument is unpersuasive. Rychak teaches that the first surfactant is present in the shell in a moles/moles ratio of from 5–90% relative to the other components, the second lipid is present in a moles/moles ration of from 0.1–99%, relative to the other shell components, and the targeting ligand is present in the shell in a moles/moles ratio of from 0.1–5%. Rychak Claims 15–18. The ranges recited in Appellant’s claims fall within these recited ranges rendering the Appeal 2021-002061 Application 14/654,650 9 ranges obvious absent evidence that the references teach away from the claimed ranges or there is evidence of unexpected results. Iron Grip Barbell, 392 F.3d at 1322. Appellant does not point to nor do we discern any teaching away from the recited ranges in the references. See Appeal Br. 7. In addition, as discussed more fully below, Appellant has not presented any persuasive evidence of unexpected results. Appellant contends that one skilled in the art would not combine the teachings of Unger and Rychak as they are directed to two different objectives and that combining the references would produce a microbubble that is unsatisfactory for its intended purpose. Appeal Br. 7–9. Appellant contends that Rychak is directed to producing a fragile microbubble that can be easily ruptured. Id. Appellant contends that Unger is directed to a stable microbubble that is not easily ruptured. Id. Appellant contends that incorporating the teachings of Unger into Rychak would result in a microbubble that would be unsuitable for Rychak’s intended purpose. Id. We find this argument unpersuasive. Both Rychak and Unger teach the preparation of microparticles for use in imaging. Rychak ¶ 14; Unger Abst. Both Unger and Rychak teach that the microparticles can be ruptured using ultrasound once the microparticles are in the target region. Unger col. 5, ll. 4–6; Rychak ¶ 22. Rychak teaches that the microparticles are allowed to accumulate in a tumor of up to 30 minutes, then observed using ultrasound, and then disrupted by a more intense ultrasound signal to release a therapeutic agent. Rychak ¶ 75. Given that the microparticles of Unger and Rychak are both used for the same purposes and may possess similar degrees of stability we find that incorporation of the teachings of Unger into Rychak would not render the microparticles unsuitable for the purpose of Rychak. Appeal 2021-002061 Application 14/654,650 10 Appellant contends that one skilled in the art would not be motivated to use the mole ratio of Unger in the microparticles of Rychak as Unger uses a negatively charged lipid which would produce different properties in the microparticle. Appeal Br. 11–14. We are not persuaded by this argument. As discussed above, the mole ratios recited in the claims fall within the ratios taught by Rychak rendering those ranges obvious. Appellant contends that Unger does not teach or suggest a negatively charged lipid covalently bound to a PEG group, and thus “a skilled person would not consider combining the teachings of Rychak and Unger in order to arrive at component (iii) of pending claims 1 and 34.” Appeal Br. 14. This argument is unpersuasive. While Unger may not teach a negatively charged lipid bonded to PEG, Rychak teaches the C18 PEG bonded element of claim 1. Rychak ¶¶ 49 and 51, claim 6. Appellant contends that the Examiner engaged in the impermissible use of hindsight in making the rejection. Appeal Br. 20. Appellant contends that one skilled in the art would need to make several selections to arrive at the claimed invention and that the references provide no guidance as to how to arrive at the claimed invention. Id. Appellant contends that the specific mole ratios recited in the claims results in the specific in vivo functions that one skilled in the art would only achieve those results starting with Rychak through the use of hindsight. Id. We have considered Appellant’s argument and the evidence of record and are not convinced that the rejection is based on the improper use of hindsight. “Any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill at the Appeal 2021-002061 Application 14/654,650 11 time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). As discussed above, the mole ratios recited in the claims fall within the ratios taught by Rychak. Finding the optimum ratios would be within the skill of one skilled in the art and does not render the claims patentable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955). We discern nothing in the rejection that is gleaned solely from Appellant’s disclosure. Appellant contend that the present invention has advantages not taught by the references and that are unexpected. Appeal Br. 21–25. We are not persuaded that the evidence of record demonstrates unexpected results sufficient to demonstrate patentability. While the Specification reports results that appear to show certain advantages of the present invention, the comparisons reported in the Specification do not compare the invention against the closest prior art, Rychak. “To be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). The only comparison of the invention with Rychak is attorney argument comparing examples in the Specification with an example in Rychak. Appeal Br. 22. As the Examiner noted, this is not a proper comparison as the binding ligands are different which would affect the binding levels achieved. Ans. 15. Appeal 2021-002061 Application 14/654,650 12 Moreover, while Appellant argues that the results are unexpected, Appellant offers no evidence to support that argument. Appeal Br. 24. “Attorney’s argument in a brief cannot take the place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Conclusion Based on the foregoing we conclude that a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70 would have been obvious to one of ordinary skill in the art at the time the invention was made over Rychak combined with Unger. CONCLUSION The Examiner’s rejection is affirmed. More specifically, the rejection of claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70 under 35 U.S.C. § 103 as unpatentable over Rychak in view of Unger is affirmed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, 70 103 Rychak, Unger 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, 70 Appeal 2021-002061 Application 14/654,650 13 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED Copy with citationCopy as parenthetical citation