Ex Parte Grabowski et alDownload PDFPatent Trial and Appeal BoardDec 21, 201612683265 (P.T.A.B. Dec. 21, 2016) 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. 12/683,265 01/06/2010 Gregory A. Grabowski 0010872/0573008 2718 26874 7590 12/23/2016 FROST RROWN TODD T T C EXAMINER 3300 Great American Tower SAIDHA, TEKCHAND 301 East Fourth Street CINCINNATI, OH 45202 ART UNIT PAPER NUMBER 1652 NOTIFICATION DATE DELIVERY MODE 12/23/2016 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): patents @ fbtlaw. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GREGORY A. GRABOWSKI and HONG DU1 Appeal 2015-007126 Application 12/683,265 Technology Center 1600 Before ULRIKE W. JENKS, JOHN G. NEW, and RYAN H. FLAX, Administrative Patent Judges. NEW, Administrative Patent Judge. 1 Appellants state the real party-in-interest is Children’s Hospital Research Foundation. App. Br. 3. Appeal 2015-007126 Application 12/683,265 DECISION ON APPEAL Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1, 4—14, and 30.2 Specifically, claims 1, 4—14, and 30 stand rejected as unpatentable under 35 U.S.C. § 112, first paragraph, for lack of adequate descriptive support. Claims 1, 4—14, and 30 also stand rejected as unpatentable under 35 U.S.C. § 112, second paragraph, as being indefinite. Claims 1, 4—14, and 30 further stand rejected as unpatentable under 35 U.S.C. § 102(a) as being anticipated by R.A. Anderson and G.N. Sando, Cloning and Expression of cDNA Encoding Human Lysosomal Acid Lipase/Cholesteryl Ester Hydrolase, 266(3:1) J. Biol. Chem. 22479—22484, (1991) (“Anderson”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellants’ invention is directed to a method to diminish and/or eliminate atherosclerotic plaques, in mammals, through direct and indirect treatment of these plaques, in situ, using suitable substances which are capable of lipid removal, primarily through hydrolysis, either by a catalytic or stoichiometric process, wherein the substance targets receptors in and/or on the cell which lead to uptake into the lysosome. Abstract. 2 Claims 2 and 3 are canceled. App. Br. 16. Claims 15—29 are withdrawn. Final Act. 1. 2 Appeal 2015-007126 Application 12/683,265 REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A pharmaceutical composition comprising a. a protein or polypeptide comprising lysosomal acid lipase or a protein or polypeptide having at least 85% sequence homology to SEQ ID No: 2; and b. a pharmaceutically acceptable carrier; wherein said protein or polypeptide is present in an amount sufficient to cause a decrease in a level of atherosclerotic plaques in a patient while minimizing undesired side effects. App. Br. 16. ISSUES AND ANALYSES We agree with, and adopt, the Examiner’s findings and conclusion that the appealed claims are prima facie anticipated over Anderson and that the Specification does not provide sufficient descriptive support for “lysosomal acid lipase” as claimed. We address the arguments raised by Appellants below. A. Rejection of the claims under 35 U.S.C. $ 112, first paragraph Issue 1 Appellants argue the Examiner erred because the claim term “lysosomal acid lipase” satisfies the written description requirement of 35 U.S.C. § 112, first paragraph despite the lack of a sequence listing. App. Br. 7. 3 Appeal 2015-007126 Application 12/683,265 Analysis Appellants point to the Office Actions of June 3, 2013, December 11, 2013, and June 24, 2014, in each of which, Appellants assert, the Examiner rejected the claims containing the term “lysosomal acid lipase” as not meeting the written description requirement of the first paragraph of 35 U.S.C. § 112. App. Br. 7. Appellants quote the Examiner as finding Appellants’ arguments are not persuasive “because a reference sequence is vital for calculating sequence homology.” Id. (quoting Final Act 8). Appellants assert that, in rejecting the claims on this ground, the Examiner relied on the MPEP and case law holdings from 1974 and 2003, and failed to recognize the holding of Falko-Gunter Falkner v. Inglis, 448 F.3d 1357 (Fed. Cir. 2006), which Appellants contend applies directly to the instant appeal. Id. According to Appellants, Falko-Gunter holds that an application need not contain a sequence listing or an express incorporation by reference statement for the written description requirement to be satisfied. Id. at 7—8. In Falko-Gunter, Appellants argue, the Federal Circuit considered whether the written description requirement was met for claims directed to a vaccine comprising a DNA polynucleotide encoding an antigen. App. Br. 8. Appellants point out that the Falko-Gunter Appellants’ Specification did not incorporate by reference any literature that described the DNA sequence or the locations of the “essential regions.” Id. Nevertheless, Appellants note, the specification was held to have met the written description requirement because accessible literature sources clearly provided the genes and the nucleotide sequences, holding that “it is the binding precedent of this court that Eli Lilly does not set forth a per se rule that whenever a claim limitation is directed to a macromolecular sequence, the specification must always 4 Appeal 2015-007126 Application 12/683,265 recite the gene or sequence, regardless of whether it is known in the prior art.” Id. (quoting Falko-Gunter, 448 F.3d at 1368). Appellants further quote Falko-Gunter as holding “that where, as in this case, accessible literature sources clearly provided, as of the relevant date, genes and their nucleotide sequences ..., satisfaction of the written description requirement does not require either the recitation or incorporation by reference (where permitted) of such genes and sequences.” Id. Appellants contend that 1) the facts of the present case fall within those of Falko-Gunter, because a sequence listing in the application is not required to satisfy the written description requirement; 2) the written description requirement is therefore met in the instant case. App. Br. 8. Appellants point out that the claims recite compositions containing SEQ ID No: 2, which, Appellants assert, corresponds to lysosomal acid lipase (“LAL”). Appellants maintain that SEQ ID No: 2 was added at the insistence of the Examiner, who found the LAL sequence was unclear without such a sequence listing. Id. Appellants assert that their Specification describes LAL in detail and, further, directly cites an accessible literature source, Anderson. App. Br. 9. According to Appellants, the state of the art at the time of filing was such that Appellants were fully in possession of the claimed invention by virtue of the reference to Anderson, and thus satisfied the written description requirement. Id. Appellants contend Anderson discloses the LAL sequence in its entirety, including numbering the amino acid positions sufficient to identify the numbering referenced by Appellants’ Specification. Id. Appellants further point out that Anderson also discloses the GenBank 5 Appeal 2015-007126 Application 12/683,265 accession number of LAL, and that it would have been within the knowledge of a person of ordinary skill in the art to thus access the sequence in full. Id. Consequently, Appellants argue, Anderson is disclosed in the Specification as an accessible reference that would have provided the genes and nucleotide sequence of LAL. Id. Appellants further argue that, with respect to the claimed sequence homology, the USPTO’s Written Description Training Materials (Revision 1, March 25, 2008) discloses that determination of variants are within the skill in the art. App. Br. 9. The Examiner responds that, with respect to incorporation by reference, 37 C.F.R. § 157(b) states: Except as provided in paragraph (a) of this section, an incorporation by reference must be set forth in the specification and must: (1) Express a clear intent to incorporate by reference by using the root words “incorporate(e)” and “reference” (e.g., “incorporate by reference”); and (2) Clearly identify the referenced patent, application, or publication. Ans. 20. The Examiner also points to 37 C.F.R. § 157(g)(2), which states: “A correction to comply with paragraph (b)(2) of this section is only permitted for material that was sufficiently described to uniquely identify the document.” Id. at 21. The Examiner next points to 37 C.F.R. § 1.57(f), which states: Any insertion of material incorporated by reference into the specification or drawings of an application must be by way of an amendment to the specification or drawings. Such an amendment must be accompanied by a statement that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 6 Appeal 2015-007126 Application 12/683,265 Ans. 21. The Examiner finds Appellants were unable to show in their Specification any statement pertaining to an “incorporation by reference” of Anderson. Consequently, the Examiner finds a clear intent to incorporate Anderson by reference is not present in Appellants’ Specification as required by 37 C.F.R. 157. Id. (also citing MPEP § 608.01). The Examiner rejects as not persuasive Appellants’ argument with respect to Falko-Gunter. Ans. 25. The Examiner finds Appellants’ claims recite homology and specific mutational modifications with respect to any of several versions of LAL, thereby leading to ambiguity even to a person of ordinary skill in the art. Id. The Examiner finds Appellants are attempting to incorporate by reference the sequence of SEQ ID No: 2, however, the Examiner finds, a person of ordinary skill in the art would find the discrepancies relating to claims directed to varying structural homologies and dissimilarities, due to the art showing different sequence versions of human LAL and the claimed homology and specific mutational modifications, resulting in different positional “mismatches” with respect to the different versions of LAL. Id. at 26. Consequently, the Examiner finds, a specific reference sequence, which was not required in Falko-Gunter, would be essential in this case. Id. The Examiner finds lysosomal acid lipases from various sources do not necessarily have the same amino acid sequences at the specific residues as claimed. Ans. 23. The Examiner finds that even human LAL (“hEAE”) from the same source can vary. Id. The Examiner points, by way of example, to AC M74775 (in which residue 153 is “P”) does not match exactly the hLAL sequence disclosed by Anderson, which discloses that residue 153 is “S.” Id. 7 Appeal 2015-007126 Application 12/683,265 Finally, the Examiner states, although the inclusion of SEQ. ID No: 2 into the claims was suggested by the Examiner, it was similarly suggested that the “incorporation by reference” be given a proper basis in Appellants’ Specification, and that no new matter be introduced. Ans. 27. We are not persuaded by Appellants’ arguments. As an initial matter, we do not agree with the Examiner that knowledge that was known in the prior art must be explicitly incorporated by reference in Appellants’ Specification. See Falko-Gunter, 448 F.3d at 1367. Rather, as our reviewing court has held: “[I]t is the binding precedent of this court that Eli Lilly does not set forth a per se rule that whenever a claim limitation is directed to a macromolecular sequence, the specification must always recite the gene or sequence, regardless of whether it is known in the prior art.” Id. (citing Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005)). Rather: The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence. The law must be applied to each invention that enters the patent process, for each patented advance is novel in relation to the state of the science. Since the law is applied to each invention in view of the state of relevant knowledge, its application will vary with differences in the state of knowledge in the field and differences in the predictability of the science. Id. at 1367—68 (quoting Capon, 418 F.3d at 1358 (Fed. Cir. 2005)). In the appeal before us, Appellants’ Specification states “LAL, a member of the lipase family, is a 372 amino acid glycoprotein that is trafficked to the lysosome via the mannose receptor system. The cDNA sequence which encodes LAL has been previously reported.” Spec. 134 (internal citations omitted). This passage also cites directly to the Anderson 8 Appeal 2015-007126 Application 12/683,265 reference. See Spec. 36. Furthermore, Anderson teaches: “The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) M74775.” Anderson 22479. The sequence provided in Figure 4 is this sequence, which is human lysosomal acid lipase (“hLAL”), is thus supported in the Specification. However, claim 1 recites, in relevant part: “A pharmaceutical composition comprising ... a protein or polypeptide comprising lysosomal acid lipase” and thus claims any lysosomal acid lipase, not limited to the hLAL sequence claimed by Anderson. Moreover, the word “comprising” indicates that additional elements of the composition may be included within the scope of the claim. The scope of claim 1, therefore, includes all LALs. Appellants’ Specification does not describe the variation in sequence homologies between hLAL and LALs from other species and, consequently, we agree with the Examiner’s conclusion that the Specification does not provide adequate written descriptive support for the claims. Issue 2 Appellants contend the Examiner erred in concluding the claims lack enablement because it would require a person of ordinary skill to conduct undue experimentation to practice them. Analysis Appellants argue the Examiner erred in finding that there was no data provided for pharmaceutical compositions for the treatment of any diseases or disorders. App. Br. 10. Appellants point to Figure 4, Table 2, and 9 Appeal 2015-007126 Application 12/683,265 [0064]-[0067] of the Specification, in which representative sections from the aortic valve of ldlr -/ mice with and without LAL treatment, and quantitative effects of LAL on the aortic valves and coronary arteries of ldlr -/ mice, are illustrated and described. Id. Appellants specifically cite 1 [0067], which discloses “[t]hese results show a major selective effect of a single fixed dose level of LAL on the presence of aortic valvular and coronary artery foam cell and progressive atherogenic lesions.” Id. Appellants contend that at least one suitable composition is thus clearly set forth in the Specification. Id. (citing, e.g., 1 51). As such, Appellants assert, no undue experimentation is required to practice the claimed composition. The Examiner responds that although the data presented in Figure 4 and Table 2 are relevant to Appellants’ arguments, Appellants’ Specification fails to address the entire scope of the claims, when given the broadest reasonable interpretation. Ans. 27—28. The Examiner finds that the claims recitation of “a protein or polypeptide having at least 85% sequence homology to SEQ ID No: 2” reasonably includes a protein or polypeptide with the requisite 85% sequence homology, but with no lysosomal acid lipase activity. Id. at 28. The Examiner finds that such an inactive protein or polypeptide has not been shown by Appellants’ Specification to be effective in a pharmaceutical composition in an amount sufficient to cause a decrease in a level of atherosclerotic plaques. Id. Appellants reply that the Examiner construes the claims to omit the limitation reciting “in an amount sufficient to cause a decrease in a level of atherosclerotic plaques in a patient.” Reply Br. 9. Appellants argue that LAL is the active agent that reduces atherosclerotic plaques and that if, as the Examiner finds, there is no lysosomal acid lipase activity, then such 10 Appeal 2015-007126 Application 12/683,265 construction improperly fails to consider each and every feature of the claims. Id. at 9—10. Appellants contend the data showing efficacy in reducing atherosclerotic plaques supports enablement of the claims. Although we find Appellants arguments persuasive with respect to this issue, our conclusion with respect to Issue 1, as explained supra, requires that we affirm the Examiner’s rejection of the claims under 35 U.S.C. § 112, first paragraph. B. Rejection of the claims under 35 U.S.C. $ 112, second paragraph Issue Appellants argue the Examiner erred in concluding that the claims are indefinite under 35 U.S.C. § 112 (second paragraph) as failing to particularly point out and distinctly claim the subject matter that Applicant regards as the invention. App. Br. 11. Analysis Appellants dispute the Examiner’s finding that “residue Ser 153” and “substitution of amino acid Pro(-6) to Thr and Gly2 to Arg” is unclear. App. Br. 11 (citing Final Act. 15). Appellants also contend the Examiner incorrectly concluded that “the claims are indefinite because it is unclear regarding the residue (153) of the reference sequence(s); and further it is not clear to which residue or position is referred to.” Id. Appellants also dispute the Examiner’s conclusion that the claims reciting the features of “lysosomal acid lipase having fewer than six N-linked acetylglycosylation residues or wherein the N-acetylglycosylation residue is oligosaccharide-terminated or wherein the oligosaccharide terminating residue is a mannose residue” are 11 Appeal 2015-007126 Application 12/683,265 “indefinite because it is unclear of the reference sequence(s) to which the limitations are related to.” Id. Appellants argue these findings and conclusions are improper because: (1) the Examiner failed to apply the applicable case law (i.e., Falko-Gunter, as discussed supra), and (2) the Examiner improperly disregarded the 37 CFR 1.132 Declaration by Dr. David Hui (the “Hui Declaration” that establishes that the claims meet the definiteness requirement of the second paragraph of 35 U.S.C. § 112. App. Br. 11. With respect to (1), Appellants repeat their argument that one of ordinary skill in the art would readily understand and have access to the referenced LAL sequence as it was cited in the Specification. App. Br. 11. With respect to (2), Appellants point to the Hui Declaration’s opinion that: [0]ne of ordinary skill in the art also would readily identify particular amino acids and/or nucleotides in view of the disclosure of the above-referenced application. In particular, Anderson provides the amino acid numbering in Figure 4, such that the residue at position 153 is identified as a serine residue, the residue at position -6 is identified as a serine residue, the residue at position 2 is identified as a glycine residue .... [and] that the disclosure of the above-referenced application, as it pertains to LAL is not merely a general description that is representative of a genus, but rather, has sufficient detail that one of ordinary skill in the art reasonably would conclude that the inventor had passion of the claimed invention. Id. at 11—12 (quoting Hui Decl. ^fl[ 12—13). Appellants argue further that the Dr. Hui opines that the disclosures of the Specification “provide [ ] sufficiently detailed relevant identifying characteristics, such that at the time the application was filed, one of 12 Appeal 2015-007126 Application 12/683,265 ordinary skill in the art readily understood the precise structure of LAL being described and appreciated that such structure was in the possession of the inventor.” App. Br. 12 (quoting Hui Decl. | 6). Appellants contend the Hui Declaration establishes that “the description provided in the ... application is more than sufficient to distinguish the claimed chemical structure of LAL from other materials.” Id. (quoting Hui Decl. 17). Appellants further assert that the Hui Declaration further opines: [T]hat the full length LAL sequence was also known to one of ordinary skill in the art at the time of filing, using the Entrz Pub Med database, available at http://www.ncbi.nlm.nih.gov/pubmed. This is a publicly available database conventionally used by those of ordinary skill in the art since well before the filing date of the instant application. Id. (quoting Hui Decl. 17) and, further, that: [T]he description provided in the ... application is more than sufficient to distinguish the claimed chemical structure of LAL from other materials and would have led one of ordinary skill in the art to conclude that applicant was in possession of the claimed invention. In particular, the ... application states that ‘ [t]he cDNA sequence which encodes LAL has been previously reported,’ citing to the Anderson reference.... The Anderson reference, which one of ordinary skill in the art would have readily accessed either online or via a library containing such widely distributed journals, clearly discloses the known and conventionally accessible amino acid sequence and the complete nucleotide sequence of LAL. Id. at 13 (quoting Hui Decl. 1 6). Finally, Appellants argue that the Hui Declaration asserts that “there is no question as to what the precise structure of LAL is and was at the time 13 Appeal 2015-007126 Application 12/683,265 of filing” and “further addresses the concern regarding the specific positions of the nucleotides.” Id. (quoting Hui Decl. 17; citing Hui Decl. 112). The Examiner responds that the variable nature of the sequences version, the vagueness of Appellants’ Figure 4, as well as the mismatch of the residues of accession number M74775 and the residues cited in the claims establish the indefmiteness of the claims. Ans. 31—32. The Examiner finds the Hui Declaration does not address the variable nature of the various sequence versions. Id. at 32. Specifically, the Examiner finds that although the Hui Declaration attests that: “In particular. Anderson provides the amino acid numbering in Figure 4, such that the residue at position 153 is identified as a serine residue, the residue at position -6 is identified as a serine residue, the residue at position 2 is identified as a glycine residue,” it is not possible to clarity the same from the unclear numbering and alignments of sequences in Figure 4 if that is the case. Ans. 32 (citing Hui Decl. 2). The Examiner finds that in Accession No. 841408, which is the LAL sequence disclosed by Anderson position 153 is not serine and, with respect to claim 6’s substitution of amino acid Pro(-6) to Thr and Gly2 to Arg, is unclear for the negative positional value 6. Ans. 32. The Examiner similarly finds claims 7—12, recite “lysosomal acid lipase having fewer than six N-linked acetylglycosylation residues or wherein the N-acetylglycosylation residue is oligosaccharide-terminated or wherein the oligosaccharide terminating residue is a mannose residue,” are indefinite because it is indefinite with respect to the positions are being referred to with respect to SEQ ID No: 2. Ans. 33. 14 Appeal 2015-007126 Application 12/683,265 We agree with Appellants concerning the limitations of claims 7—12, because they do not require a specific position on the claimed SEQ ID No: 2. Moreover, the claims recite: a protein or polypeptide comprising lysosomal acid lipase or a protein or polypeptide having at least 85% sequence homology to SEQ ID No: 2. Applying the broadest reasonable interpretation of the claim language, we interpret this limitation to mean either a protein or polypeptide that demonstrates acid lipase activity and that is derived from a lysosome of a eukaryotic cell or a cell with 85% sequence homology to SEQ ID No: 2. The latter is easily determined quantitatively. The former would also be easily recognized by a person of ordinary skill in the art. We consequently conclude that the claims, when read in view of the Specification, define the scope of the invention with sufficient clarity and distinction and we consequently reverse the Examiner’s rejection upon this ground. C. Rejection of the claims under 35 U.S.C. $ 102(a) Issue Appellants argue the Examiner erred because Anderson does not disclose a “pharmaceutically acceptable carrier” as required by the claims. App. Br. 14. Analysis Appellants contend there is no showing that a pharmaceutically acceptable carrier is disclosed by Anderson. App. Br. 14. At best, Appellants argue, the reference states merely that “[w]e succeeded in purifying small amounts of the secreted form of HLAL” and that “purified 15 Appeal 2015-007126 Application 12/683,265 lipase was applied to HLAL-deficient WD or CESD fibroblasts in culture.” Id. According to Appellants, there is no showing by the Examiner of any pharmaceutically acceptable carrier. Id. Furthermore, Appellants argue, the claims relate to an amount of LAL “sufficient to cause a decrease in a level of atherosclerotic plaques in a patient while minimizing undesired side effects.” App. Br. 14. Appellants contend that such an amount is not disclosed in Anderson. Id. The Examiner responds that, regardless of what LAL is used for, the LAL disclosed by Anderson in buffer or water may serve as a pharmaceutical carrier and provides a composition that is no different than what is claimed. Ans. 34. The Examiner also finds that a variation in the amount of a protein or polypeptide is not considered an altered property of the product. Ans. 34. The Examiner finds the composition taught by Anderson (hLAL) in solution comprises the claimed composition, regardless of its use. Id. Therefore, the Examiner finds the amount of hLAL, or its use in decreasing the level of atherosclerotic plaques in a patient is not accorded patentable weight. Id. We are not persuaded by Appellants’ arguments. Anderson teaches: “The [transfected] cells were harvested by scraping from the plates, rinsed in phosphate-buffered saline, and pelleted by a brief centrifugation. Extracts were prepared by sonication of cells in saline. Assays of acid lipase and 13- hexosaminidase activity and of cell protein content were conducted as was previously described.” Anderson 22480 (emphasis added; internal citations omitted). We agree with the Examiner that a person or ordinary skill in the art would recognize that phosphate-buffered saline, in which the hLAL is suspended, would constitute a pharmaceutically acceptable carrier, as 16 Appeal 2015-007126 Application 12/683,265 required by the claims. Furthermore, we agree that claim 1 ’s recitation of “present in an amount sufficient to cause a decrease in a level of atherosclerotic plaques in a patient while minimizing undesired side effects” speaks only to the amount required to achieve an intended use of the otherwise structurally complete composition claims and is therefore not limiting on the claimed composition. We consequently affirm the Examiner’s rejection on this ground. DECISION The Examiner’s rejection of claims 1, 4—14, and 30 as unpatentable under 35U.S.C. § 112, first paragraph, as lacking sufficient descriptive support is affirmed. The Examiner’s rejection of claims 1, 4—14, and 30 as unpatentable under 35 U.S.C. § 112, first paragraph, lacking enablement is reversed. The Examiner’s rejection of claims 1, 4—14, and 30 as unpatentable under 35 U.S.C. § 112, second paragraph, is reversed. The Examiner’s rejection of claims 1, 4—14, and 30 as unpatentable under 35 U.S.C. § 102(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)(l)(iv). AFFIRMED 17 Copy with citationCopy as parenthetical citation