Albert AbrahamDownload PDFPatent Trials and Appeals BoardSep 6, 201913320289 - (D) (P.T.A.B. Sep. 6, 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. 13/320,289 11/14/2011 Albert Abraham BHC 097002 BAYR6427 7634 71396 7590 09/06/2019 BAYER HEALTHCARE LLC (AH) 1 Bayer Drive Indianola, PA 15051 EXAMINER POPA, ILEANA ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 09/06/2019 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): USPOCCS@BAYER.COM PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte ALBERT ABRAHAM1 ____________ Appeal 2018-005406 Application 13/320,289 Technology Center 1600 ____________ Before ERIC B. GRIMES, DEBORAH KATZ, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. § 134(a) involving claims to methods for administering an immunomodulator composition to an egg in ova (aka, in ovo).2 The Examiner’s rejection of claims 34–40 and 49 under 35 U.S.C. § 103(a) remains appealed.3 We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellant identifies the real party-in-interest as, “Bayer Intellectual Property GMBH.” Appeal Br. 1. 2 The Specification refers to “in ovo” administration and the claims recite “in ova” administration, which are synonymous terms. 3 As of the filing of this appeal, claims 1–26 and 28–33 stand cancelled and, in the Reply Brief, Appellant withdrew the appeal as to claims 27, 41–48, and 50. Final Action 2; Reply Br. 1. Appeal 2018-005406 Application 13/320,289 2 In the Reply Brief, Appellant states, “Appellant requests that the appeal be withdrawn with respect to claims 27, 41 through 48, and 50 and proceed on the basis of claim 35 and claims 34, 36 through 40, and 49 dependent therefrom.” Reply Br. 1. We, therefore, summarily dismiss this appeal with respect to claims 27, 41–48, and 50 and herein consider the outstanding rejection as it applies to claims 34–40 and 49. STATEMENT OF THE CASE The Specification states, “[t]he present invention relates to a method of immune activation in an avian species.” Spec. 1:3.4 The Specification further states: Some live viral vaccines can be administered in eggs before the birds hatch. This procedure is referred to as “in ovo vaccination.” The in ovo vaccinated birds develop resistance to the target disease. However, many vaccines used for hatched birds cannot be used for in ovo vaccination due to the embryonic pathogenicity of the vaccine agents. Late stage embryos are highly susceptible to infection with most vaccine viruses examined. Id. at 2:7–11. Further, “a need exists for a method of eliciting a non-antigen- specific immune response that enhances protection of birds from infectious disease and is easy to administer.” Id. at 2:20–22. As set forth below, the claimed invention is directed to administering a composition including a cationic liposome and a non-coding (for immunogen) nucleic acid molecule to elicit such an immune response. The Specification states, “[a] suitable liposome delivery vehicle comprises a lipid 4 When referencing the Specification or “Spec.” we refer to the Specification filed as PCT/EP2010/002809 on November 14, 2011. Appeal 2018-005406 Application 13/320,289 3 composition that is capable of delivering nucleic acid molecules to the tissues of the treated subject,” and explains, “[s]uitable liposomes include any liposome, such as those commonly used in, for example, gene delivery methods known to those of skill in the art,” for example, “cationic liposome compositions.” Spec. 9:29–30, 10:21–27. The Specification states, “[a] suitable nucleic acid molecule includes any nucleic acid sequence such as coding or noncoding sequence, and DNA or RNA,” specifically, “such as a plasmid vector without a gene insert.” Id. at 11:1–8. The Specification states, “[c]omplexing a liposome with a nucleic acid molecule may be achieved using methods standard in the art.” Id. at 11:15–16. The Specification states, “protecting a subject from a disease is accomplished by eliciting an immune response in the member of the avian species by inducing a beneficial or protective immune response.” Id. at 14:20–22. Independent claim 27 and dependent claim 35, reproduced below, are representative: 27. A method of increasing hatchability of an embryonated chicken egg comprising administering in ova to the egg from about 0.05 to about 10 micrograms of an immunomodulator composition prior to hatching, wherein the immunomodulator composition comprises: a. a cationic liposome delivery vehicle; and b. a nucleic acid molecule that does not code for an immunogen, wherein said administration increases the hatchability of said egg following challenge with Escherichia coli. 35. The method of claim 27, wherein the nucleic acid molecule is a DNA plasmid. Appeal 2018-005406 Application 13/320,289 4 Supplemental Appeal Br. 2 (Claims Appendix). Although the rejection of claim 27 is no longer appealed (see supra n.3), claims 34–40 and 50 depend therefrom. The following rejection is on appeal: Claims 27 and 34–50 stand rejected under 35 U.S.C. § 103(a) over Gomis,5 Dow,6 and Zaks.7 Final Action 9. FINDINGS OF FACT We adopt the Examiner’s findings of fact and rationale on obviousness as set forth in the Final Action and Answer. Final Action 2–5; Answer 3–15. The following findings of fact highlight certain evidence: FF1. Gomis discloses “[o]ligodeoxynucleotides (ODN) containing cytosine-phosphodiester-guanine (CpG) motifs [“CpG ODN”] have been shown to be effective immunoprotective agents” and discloses a study where “embryonated [chicken] eggs that had been incubated for 18 or 19 days, received 50 µg CpG ODN.” Gomis 813 (abstract). FF2. Gomis discloses that chick groups that received CpG ODN, either by intramuscular or in ovo routes, had significantly higher survival rates (P < 0.0001) [post- 5 Susantha Gomis et al., Protection of Neonatal Chicks Against a Lethal Challenge of Escherichia coli Using DNA Containing Cytosine- Phosphodiester-Guanine Motifs, 48 AVIAN DISEASES 813–822 (2004) (“Gomis”). 6 Steven W. Dow, DVM, PhD, Liposome-Nucleic Acid Immunotherapeutics, 5(1) EXPERT OPIN DRUG DELIV. 11–24 (2008) (“Dow”). 7 Karen Zaks et al., Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes, 176 J. IMMUNOL. 7335–45 (2006) (“Zaks”). Appeal 2018-005406 Application 13/320,289 5 E. coli challenge]. Bacterial counts in air sacs were significantly lower when birds or embryos were treated with CpG ODN as compared with controls. A dose as low as 10 µg of CpG ODN, administered intramuscularly, was able to protect birds significantly against E. coli challenge, thus “[t]his is the first time that CpG ODN has been demonstrated to have an immunoprotective effect against a bacterial infection in chicks following in ovo delivery.” Gomis 813 (abstract); see also id. at 814 (“The objective of this study was to determine the effect of CpG ODN, delivered either intramuscularly or in ovo, as an immunostimulant in broiler chicks, using an E. coli infection model.”). FF3. Gomis teaches that “Escherichia coli causes a variety of disease syndromes in poultry, including yolk-sac infection [i.e., an infection in ovo], omphalitis, respiratory tract infection, swollen head syndrome, septicemia, and cellulitis.” Gomis 814. FF4. Gomis states, “further work on delivery mechanisms (such as in ovo administration with encapsulation for the slow release of CpG ODN, and aerosol or oral delivery) are necessary to expand the utility of CpG ODN use in the poultry industry,” which suggests that the CpG ODN should be complexed with another component for encapsulation to control administration. Gomis 820. FF5. Dow teaches that “liposome-nucleic acid complexes also show promise for immunotherapy of acute . . . bacterial infections,” and “cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.” Dow 1 (abstract); see also id. at 9–11 (concluding that “liposomal delivery Appeal 2018-005406 Application 13/320,289 6 offers important advantages over treatment with the innate immune receptor agonist alone” and there are “major advantages” in complexing cationic liposomes with immunotherapeutics based on nucleic acids). FF6. Dow teaches that “[l]iposomes enhance innate immune activation by nucleic acids,” and, specifically, cationic liposomes complexed with bacterial DNA, CpG ODN, and plasmid DNA. Dow 3–4. FF7. Zaks teaches that “[c]omplexing . . . plasmid DNA to cationic liposomes markedly potentiates their ability to activate innate immunity.” Zaks 7335 (abstract). DISCUSSION “[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. [Once] . . . that burden is met, the burden of coming forward with evidence or argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). Arguments made by Appellants in the Appeal Brief and properly presented in the Reply Brief have been considered; arguments not so-presented are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived.”). Appeal 2018-005406 Application 13/320,289 7 CLAIM INTERPRETATION The Patent Office applies the broadest reasonable construction standard in prosecution proceedings. Cuozzo Speed Tech., LLC v. Lee, 136 S. Ct. 2131, 2145 (2016). A claim preamble does not further limit claims if it merely states a purpose or intended use of subject matter, but, if the preamble expresses an “essential” characteristic of the invention necessary to point out the defined invention, it may be said to “give life and meaning” to the claims and, thereby, be considered a limitation. Kropa v. Robie, 187 F.2d 150, 152 (CCPA 1951). Further, “[w]here . . . a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation.” Rowe v. Dror, 112 F.3d 473, 478 (Fed. Cir. 1997). Moreover, as explained at MPEP § 2111.04, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” See Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329 (Fed. Cir. 2005) (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003)). Much of the dispute on appeal focuses upon whether the claims require improved chicken hatchability after eggs are challenged with E. coli. As noted above, independent claim 27 (and, therefore, its dependent claims), in its preamble, states that its claimed method is for “increasing hatchability of an embryonated chicken egg,” and, as a concluding “wherein” clause, recites that the administration step “increases the hatchability of said egg following challenge with Escherichia coli.” Thus, an issue presented in this Appeal 2018-005406 Application 13/320,289 8 case is whether, or to what extent, this claim language limits the respective claims. As noted above, a preamble will not be considered a claim limitation where it merely states a purpose or intended use of the subject matter of the claim’s body and, also, will not be considered a claim limitation where the body of the claim recites a complete structure or method. Here, the preamble of claim 27 recites an intended use or result/purpose of the claimed method. And, the body of the claim, i.e., that portion following the transition claim term “comprising,” recites a complete method including the single step of administering a specific composition at a specific dosage range. Therefore, the preamble of the claim is not a limitation. As also noted above, a “wherein” (or “whereby”) clause in a claim does not limit a claim where it merely identifies an intended result of an affirmative method step recited by the claim. Here, the step recited by claim 27, i.e., administering the claimed composition to a chick in ova within a specific dosage range, is a complete method regardless of its intended result. The claim does not recite an affirmative step of challenging such a therapeutically treated egg with E. coli, but only that the result of such an administration step is that it “increases the hatchability of said egg following challenge with Escherichia coli.” Whether or not the egg is ever challenged with E. coli, the administration step, which is the sole step of the claimed method, would not change and its results would be effected. Therefore, the “wherein” clause of claim 27 does not limit the claim. We note the recent Federal Circuit decision in Allergan Sales, LLC v. Sandoz, Inc., where two “wherein” clauses of a claim were held to have been Appeal 2018-005406 Application 13/320,289 9 correctly construed by district court to be limitations. Allergan Sales, LLC v. Sandoz, Inc., --- F.3d ---, 2019 WL 4063570 (Fed. Cir. Aug. 29, 2019). The wherein clauses in Allergan Sales related to (1) the effectiveness of an administered glaucoma or ocular hypertension therapeutic formulation given twice daily as compared to another therapeutic formulation given three times daily and (2) the reduction of adverse events. On their face, such wherein clauses share some similarities with that of the present claims because all appear to merely recite some intrinsic functionality or intended result of a claimed administration step. Moreover, in Allergan Sales, as here, the patent applicant (cum-patent owner) argued during prosecution that the wherein clauses were limitations that distinguished over the prior art. See id. at *4. However, we find the current case distinguishable from Allergan Sales. First, in Allergan Sales, the characteristics of the wherein clauses were argued during prosecution to be “unexpected results” that was evidence of non-obviousness. Id. Second, the Examiner in the application that would become the patent-in-suit in Allergan Sales “explicitly relied on the ‘wherein’ clauses in explaining why the claims of the Patents-in-Suit were ‘novel and non-obvious over the prior art,’” meaning the evidence of unexpected results was persuasive of patentability. Id. These facts were important to the Federal Circuit’s affirmance in Allergan Sales. Id. at *4– *5. Here, such facts are not present. Here, Appellant has not presented persuasive evidence that the claimed increase in hatchability of a treated egg following a challenge with Escherichia coli would have been an unexpected result as compared to the closest prior art. It follows that, here, the Examiner has not relied upon such evidence to find the claims non-obvious. Appeal 2018-005406 Application 13/320,289 10 In fact, based on her review of the Specification, here, the Examiner determined that Appellant’s claimed invention and its activation of an innate immune response in embryonic chicks, which results in potentially improving hatchability if eggs are challenged with E. coli, was not unexpected. See Answer 9–14. OBVIOUSNESS ANALYSIS “The combination of familiar elements [or steps] according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem; it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). “[T]he test of obviousness is not express suggestion of the claimed invention in any or all of the references[,] but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” In re Rosselet, 347 F.2d 847, 851 (CCPA 1965) (emphasis in original). “[T]he analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR, 550 U.S. at 418. Where . . . the claimed and prior art products are identical or substantially identical . . . the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. § 102, on Appeal 2018-005406 Application 13/320,289 11 ‘prima facie obviousness’ under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations and footnote omitted). “It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990). With these standards in mind and in view of our claim interpretation above, we address the Examiner’s rejections and Appellant’s arguments there-over. The Examiner determined that claims would have been obvious over the Gomis, Dow, and Zaks combination. See Final Action 2–5, and Answer 3–15 (collectively citing Gomis 813 (abstract), 816, 820, 821; Dow 1 (abstract), 3–4; Zaks 7335 (abstract), 7336, 7341). To summarize, it is the Examiner’s position that Gomis teaches the stimulation of the innate immune system (non-specific) of unhatched chickens to protect against E. coli infection (we note, Gomis discloses E. coli can infect chick in ovo) by administering in ovo a composition of CpG ODN, which is a non-coding (for immunogen) nucleic acid molecule; while Gomis teaches its in ovo dosage was 50 µg, it also taught a 10 µg dosage (provided intramuscularly) was similarly effective, which suggests the claimed dosage. See FF1–FF4. The Examiner notes that Gomis does not disclose that CpG ODN is administered with a cationic liposome, but takes the position that it would have been obvious for the skilled artisan to look to Dow for such a teaching because it disclosed that administering a cationic liposome-nucleic acid molecule complex (and cationic liposome-DNA plasmid complex) provided Appeal 2018-005406 Application 13/320,289 12 significant advantages in therapeutic immune-stimulation. See FF5–FF6. The Examiner also notes that Gomis does not disclose that an immune- stimulating nucleic acid molecule can be a plasmid DNA, but takes the position that it would have been obvious for the skilled artisan to look to Zaks for such a teaching because Zaks discloses that liposomes can be complexed with both plasmid DNA and CpG ODN to elicit enhanced immune response. See FF7. We discern no error in the Examiner’s determinations and, as noted above, adopt the Examiner’s findings of fact and rationale on obviousness. Appellant argues that the Examiner’s rejection relies on an inherency theory that the claimed increased hatchability after an egg’s challenge with E. coli would result from Gomis’s disclosed in ovo CpG ODN administration, but that it would have been impossible for the skilled artisan to determine whether such a result would necessarily occur. Appeal Br. 4–5. Appellant argues Gomis’s composition is not the same as that claimed (it does not include a liposome), so there can be no basis for such a determination. Id. Appellant also argues that Gomis did not disclose challenging eggs with E. coli, but only hatched chicks, which also forecloses a determination under an inherency theory. Id. at 6–11. In a related argument, Appellant contends the skilled artisan would not have had a reasonable expectation of successfully inoculating chicken embryos to result in increased hatchability. Id. at 11. These arguments are not persuasive. As discussed above, the claim language in the preamble and in the wherein clause relating to increased hatchability after E. coli challenge does not limit the claims. Therefore, Appeal 2018-005406 Application 13/320,289 13 Gomis’s lack of teaching focusing on such a result is not determinative. Gomis discloses the same administration timing, using a nucleic acid molecule, to the same organism as claimed. Gomis also suggests the claimed dosage to be administered and teaches that it elicited immunoprotection against E. coli infection. Dow and Zaks would have been obvious to combine with Gomis as they are related to the same general treatment and intended results as Gomis, and they teach or suggest complexing a plasmid DNA with a cationic liposome, as claimed. Based on the disclosures of Gomis, Dow, and Zaks, a skilled artisan would have reasonably expected to successfully administer such a therapeutic plasmid DNA-cationic liposome complex to chickens in ova and that such administration would protect the embryonic chicks from E. coli. by stimulating an immunoprotective response against infection by the bacteria. See supra Findings of Fact; see also Best, 562 F.2d at 1255; and Woodruff, 919 F.2d at 1578. Regarding claim 35, specifically, Appellant notes it requires using a plasmid DNA as a nucleic acid in the administered composition, but reiterates the aforementioned argument that the cited prior art does not discuss pre-hatch innate immunity for increasing hatchability. Id. at 12. This argument is not persuasive. For the reasons discussed above regarding claim 27, claim 35 also would have been obvious over the combination of Gomis, Dow, and Zaks. As noted above, the prior art combination made it obvious to use a plasmid DNA as the nucleic acid molecule of claim 27, as required by claim 35. Furthermore, as noted above, the claims’ recited increased hatchability is not a limitation. Appeal 2018-005406 Application 13/320,289 14 In the Reply Brief, Appellant argues that Gomis does not teach cationic liposomes and that this component is an important component of the claims. Reply Br. 3. This argument is not persuasive. The rejection is over the combination of Gomis, Dow, and Zaks, not Gomis individually. “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). Here, it would have been obvious to combine Gomis with Dow and Zaks and both Dow and Zaks teach or suggest the advantages of complexing a nucleic acid molecule or plasmid DNA with a cationic liposome to stimulate an immunoresponse, which would have rendered the claimed invention obvious. As noted above, we agree with and adopt the Examiner’s findings of fact and rationale regarding the obviousness of the claims. We discern no error in the Examiner’s determinations, which we find present a prima facie case for the claims’ obviousness over the cited prior art combination. We have considered Appellant’s arguments over the rejections in their entirety, but find them unpersuasive. Appeal 2018-005406 Application 13/320,289 15 SUMMARY The obviousness rejection of claims 34–40 and 49 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). AFFIRMED Copy with citationCopy as parenthetical citation