Thomas Skold

Patent Trials and Appeals Board

Mar 16, 2022

2021002524 (P.T.A.B. Mar. 16, 2022)

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. 11/616,658 12/27/2006 Thomas Skold SKD001 2891 39731 7590 03/16/2022 Moser Taboada / Art Jackson 1030 BROAD STREET, SUITE 203 SHREWSBURY, NJ 07702 EXAMINER WESTERBERG, NISSA M ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 03/16/2022 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@mtiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte THOMAS SKÖLD Appeal 2021-002524 Application 11/616,658 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDAMN, and TAWEN CHANG, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 64, 72, 77-81, and 83-91. 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. Appellant identifies the real party in interest as the inventor, Thomas Sköld. Appeal Br. 3. Appeal 2021-002524 Application 11/616,658 2 STATEMENT OF THE CASE According to the Specification, [t]he present application concerns oral, pulmonary and transmucosal delivery compositions that contain aqueous mixtures of three types of lipids: (1) phospholipids or certain similar lipids, (2) fatty acids, and (3) bilayer- stabilizing steroids. The variety of lipid structures that these lipids may form are believed to facilitate transport across mucosal membranes or epithelial tissue of intestines. In certain embodiments, the lipid structures are controlled so that the compositions contain one or both of two types of lipid aggregates, bilayer-enclosed vesicles and lipid particles. . . . In some embodiments, the transmucosal delivery composition includes a conjugate of a lipid-phase anchoring hydrophobic moiety and a flexible, soluble polymer. Such conjugates have been thought to be contraindicated for transdermal compositions. Spec. ¶ 4. CLAIMED SUBJECT MATTER The claims are directed to a systemic delivery composition. Claim 84 below is illustrative: 84. A systemic delivery composition consisting essentially of: a composition formed by drying to a dry form by lyophilization to remove water of an intermediate composition comprising an aqueous carrier; a lipid component suspended in the aqueous carrier comprising lipids consisting essentially of 20-50 mol % type A lipid, 30-50 mol % free fatty acid, and 22-35 mol % bilayer-stabilizing steroid(s), wherein Appeal 2021-002524 Application 11/616,658 3 type A lipid is one or more of any of phospholipid, ceramide(s) sphingomyelin(s), glucocerebroside(s) and conjugate(s) of (i) lipid-phase anchoring hydrophobic moieties and (ii) flexible, soluble polymers, wherein the lipid-phase anchoring hydrophobic moieties are phospholipid, ceramide(s), sphingomyelin(s) or glucocerebroside(s), more than 90 mole % of the type A lipid has a head group with no net charge; and formulated in the aqueous carrier to have: (i) a lipid particle component comprising particles of said lipids and having average diameter of 1 micron or more, said particles being surrounded by a lipid monolayer, and (ii) a vesicle component comprising vesicles enclosed by a single lipid bilayer, the bilayers comprising said lipids; sugar-based lyophilization protective agent(s) in a lyophilization protective amount, and a bioactive agent, wherein the type A lipid comprises (i) conjugate(s) of lipid-phase anchoring hydrophobic moieties and flexible, soluble polymers and (ii) other type A lipid(s), wherein the contribution of the lipid anchor portion of the conjugate to the lipid component is 5 mole % or less; wherein the delivery composition has been formulated for oral delivery by encapsulation, or coating, wherein the delivery composition is essentially lacking in cell-surface disruptors, wherein the bioactive agent has MW about 1000 or less and an octanol-water partition coefficient of 10 or higher, Appeal 2021-002524 Application 11/616,658 4 wherein 1 mole % or more of the bioactive agent is associated with the particles of said lipids, and 1 mole % or more of the bioactive agent is associated with the vesicles, and wherein, upon reconstitution with water the reconstituted composition has (i) the lipid particle component comprising particles of said lipids, and (ii) the vesicle component comprising vesicles comprising said lipids, wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization. Appeal Br. 53-54 (Claims App.). REJECTION(S) A. Claims 64, 72, 77-81, and 83-91 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. Ans. 3-5. B. Claims 64, 72, 77-81, and 83-91 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA), second paragraph, as being indefinite. Ans. 5-6. C. Claims 64, 72, 77-80, 84, 85, 87, 88, 90, and 91 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Sköld,2 Yoshioka,3 Choi,4 Katinger,5 and Schmidt.6 Ans. 6-14. 2 Sköld, US 2004/0009213 A1, published Jan. 15, 2004. 3 Yoshioka et al., US 5,593,622, issued Jan. 14, 2991 (hereinafter “Yoshioka”). 4 Choi et al., US 5,820,873, issued Oct. 13, 1998 (hereinafter “Choi”). 5 Katinger et al., US 5,942,245, issued Aug. 24, 1999 (hereinafter “Katinger”). 6 Schmidt et al., US 5,817,334, issued Oct. 6, 1998 (hereinafter “Schmidt”). Appeal 2021-002524 Application 11/616,658 5 D. Claims 81, 83, 86, and 89 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Sköld, Yoshioka, Choi, Katinger, Schmidt, and Scott.7 Ans. 14-15. E. Claims 64, 72, 77-80, 84, 85, 87, 88, 90, and 91 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Sköld, Yoshioka, Choi, Katinger, Schmidt, and Özer.8 Ans. 15-17. F. Claims 81, 83, 86, and 89 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Sköld, Yoshioka, Choi, Katinger, Schmidt, Özer, and Scott. Ans. 17-18. OPINION A. Lack of Written Description (claims 64, 72, 77-81, 83-91) 1. Issue The Examiner asserts that the claim limitation, “sugar based lyophilization protective agent that is present in a lyophilization protective amount,” constitutes new matter, because the Specification only discloses 5 specific sugars (i.e., sucrose, raffinose, maltose, lactose, and trehalose) as lyophilization protective agents. Ans. 3-4. The Examiner further asserts: That the protective agent is present in an amount that results in a particular protective function (e.g., maintenance of the size distribution of the lipid 7 Scott et al., US 2004/0034336 A1, published Feb. 19, 2004 (hereinafter “Scott”). 8 Yekta Özer et al., Influence of Freezing and Freeze-drying on the Stability of Liposomes Dispersed in Aqueous Media, 34 ACTA PHARMACEUTICAL TECHNOLOGICA 129 (1988) (hereinafter “Özer”). Appeal 2021-002524 Application 11/616,658 6 structures) was not disclosed in the application as originally filed. Each independent claim has also been amended to recite that the “size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization” (emphasis added). The section cited for support indicates that when reconstituted with water, “[t]he size of the aggregates, and the distribution of lipid between the two types of aggregates (if both present), may shift somewhat with reconstitution”. This does not provide support for a “similar” size distribution of the particles and vesicles after reconstitution as presently claimed. The distribution discussed in the specification related to the distribution of lipids between the two types of aggregates. “Similar” and a somewhat shift of the distribution are not the exact same scope and therefore this addition is also new matter. Ans. 4. Finally, the Examiner asserts that the limitation in claim 91 requiring “the preparation of a solid, dry form by lyophilization of the recited composition” constitutes new matter. Ans. 4-5. Appellant contends that a skilled artisan would “recognize that sugar- based protective agents are described” and that “it is clear that the art has recognized the protective effects of the protective agents . . . described.” Appeal Br. 45-47. With respect to size of the reconstituted particles and vesicles after lyophilization, Appellant contends that the Specification teaches that “[t]he size of the aggregates, and the distribution of lipids between the two types of aggregates[], may shift somewhat with reconstitution.” Appeal Br. 47. Appellant contends that a skilled artisan “can recognize from the art that ‘shifting somewhat’[] means sifting to an acceptable minimum amount” and Appeal 2021-002524 Application 11/616,658 7 that “the knowledge in the art establishes that a 21% increase may be acceptable, while a 25% increase is not.” Id. As to the limitation, “drying to a dry, solid form by lyophilization,” Appellant asserts that the prior art of record “clearly shows that freeze- drying/lyophilization means drying to a solid.” Appeal Br. 50. The issue with respect to these rejections is whether a preponderance of the evidence of record supports the Examiner’s conclusion that the claims fail to comply with the written description requirement with regard to the claim limitations of “sugar-based lyophilization protective agent(s) in a lyophilization protective amount,” “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization,” and “drying to a dry, solid form by lyophilization.” 2. Analysis a) “sugar-based lyophilization protective agent(s) in a lyophilization protective amount” We agree with Appellant that the application as originally filed adequately described “sugar-based protective agent(s) in a lyophilization amount.” As the Examiner acknowledges, the Specification discloses that “[l]yophilization can be done with added protective agents, such as sucrose, raffinose, maltose, lactose, trehalose, or the like.” Spec. ¶ 70. The Examiner asserts, however, that the Specification’s recitation of “5 specific sugars, 4 disaccharides and 1 trisaccharide,” does not provide adequate support for the limitation at issue, because ‘[s]ugar-based protective agents’ encompasses the specific sugars enclosed but is much broader as it encompasses any mono-, di-, tri-, oligo- or polysaccharide and compounds Appeal 2021-002524 Application 11/616,658 8 that are ‘based’ on sugars such as sugar alcohols that are cryoprotective.” Ans. 4. We are not persuaded. Although the Examiner is correct that the Specification only discloses specific species rather than the claimed genus, the Federal Circuit has held that a genus is sufficiently described by “disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014); see also Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002) (explaining that the written description requirement can be met by disclosing “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics”). We find that the Specification discloses a representative number of species falling within the genus in that all the species contain the structural feature (i.e., are sugar-based) that is correlated with the function of cryoprotection. The Examiner also asserts that the application as originally filed does not disclose that “the protective agent is present in an amount that results in a particular protective function (e.g., maintenance of the size distribution of the lipid structures).” Ans. 4. To the extent the Examiner’s assertion is that the Specification does not disclose a “lyophilization protective amount” of a sugar-based lyophilization protective agent, we are not persuaded because the Specification describes the use of sugars such as sucrose, raffinose, maltose, lactose, and trehalose as protective agents in lyophilization. Spec. Appeal 2021-002524 Application 11/616,658 9 ¶ 70. However, as discussed further below, we agree that the application as originally filed does not adequate describe the limitation “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization.” b) “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization” Appellant does not dispute that the only disclosure in the Specification relevant to the limitation, “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization,” appear in paragraphs 70 and 71, which states: In certain embodiments, the delivery composition is dried to allow formulation in dry forms, such as tablets or powder-filled capsules. Drying is typically accomplished by lyophilization. Lyophilization can be done with added protective agents, such as sucrose, raffinose, maltose, lactose, trehalose, or the like. Coatings for delivering such dry powders into various parts of the intestine are known in the art. . . . Where constituted in vesicles or particles prior to lyophilization, it is anticipated that these structures will be reconstituted upon addition of water, such as water from the site of administration. The size of the aggregates, and the distribution of lipid between the two types of aggregates (if both present), may shift somewhat with reconstitution. Spec. ¶¶ 70-71; Appeal Br. 47. We agree with the Examiner that the above disclosure does not reasonably convey to a skilled artisan the inventors were in possession of a composition wherein, upon reconstitution with water after lyophilization, Appeal 2021-002524 Application 11/616,658 10 “the size of the particles and vesicles reconstitute to a distribution similar to that found prior to lyophilization.” In particular, the statement in the Specification regarding “shift[ing] somewhat” indicates that the size of the aggregates and the distribution of lipid between the two types of aggregates may change “to some extent” when reconstituted after lyophilization.9 However, we are not persuaded that this disclosure would reasonably convey to a skilled artisan that the shift in the size of the lipid aggregates would be such that the distribution of particle and vesicle size in the composition would remain similar to that found prior to lyophilization. In this regard, we further note that, although the claim discusses similarity in the distribution of size of the particles and vesicles, the Specification discusses only the size of the aggregates and the distribution of lipid between different types of aggregates. Appellant contends that the disclosure above “teaches preserving the size [of the lipid aggregates] to an extent recognized as acceptable in the art.” Appeal Br. 48. Appellant contends that Katinger shows different types of lipid bodies have different effectiveness in drug delivery; thus, a skilled artisan “would recognize the importance of maintaining size to maintain biological effect” and would look to prior art for guidance. Appellant contends that “Tardi teaches that somewhere less than 20 mol% is where cholesterol causes trouble,” that Tardi’s Figure. 6A shows that “20% [cholesterol] yields a 25% increase in liposome size,” and that “[f]rom calculations based on [Schmidt] it appears that Tardi found a 21% size 9 See, e.g., “somewhat.” DICTIONARY.COM, https://www.dictionary.com/browse/somewhat (last visited Feb. 28, 2022). Appeal 2021-002524 Application 11/616,658 11 increase (from control) to be acceptable[], while a 36% increase . . . was not.” Id. Appellant concludes that “the knowledge in the art establishes that a 21% increase [in liposome size] may be acceptable, while a 25% increase is not,”10 and argues that, “[a]ccordingly, the art provides a basis for determining if a size distribution that is similar to that found prior to lyophilization.” Id. We acknowledge that “[t]he ‘written description’ requirement must be applied in the context of the particular invention and the state of the knowledge.” Capon v. Eshhar, 418 F.3d 1349, 1358 (Fed. Cir. 2005). In Capon, for example, the Federal Circuit held that the nucleotide sequences of certain chimeric genes need not be fully presented when nucleotide sequences of the component DNA are known. Id. In this case, however, we are not persuaded that the degree of shift in the distribution of the size of particles and vesicles in Appellant’s composition is known in the art. Even if the distribution were obvious, a “description that merely renders the invention obvious does not satisfy the [written description] requirement.” 10 Appellant contends that exhibit to the Supplemental Declaration of Thomas Sköld under 37 C.F.R. § 1.132 shows that “Appellant’s most successful formulations preserved the vesicle portion to within about 10% of the control size.” Appeal Br. 48. Assuming for the sake of argument that the exhibit in fact presents such data and that “preserv[ing] the vesicle portion [of the composition] to within 10% of the control size” adequately supports the limitation at issue, information needed to satisfy 35 U.S.C. § 112, first paragraph, must be disclosed in the specification, not in a later- filed declaration. In re Buchner, 929 F.2d 660, 661 (Fed. Cir. 1991) (“§ 112 requires that, unless the information is well known in the art, the application itself must contain this information; it is not sufficient to provide it only through an expert’s declaration.”). Appeal 2021-002524 Application 11/616,658 12 Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010). Neither are we persuaded by Appellant’s attorney argument that a skilled artisan would have understood the disclosures in the cited paragraphs of the Specification as describing a shift in the size of the lipid aggregates “recognized as acceptable in the art.” As an initial matter, “[a]ttorneys’ argument is no substitute for evidence.” Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989). Moreover, as discussed below in our analysis of the indefiniteness rejection, Appellant does not persuade us that there is a shift in distribution of lipid vesicle and particle size that is “recognized as acceptable” in the art. Accordingly, we affirm the Examiner’s rejection of claims 64, 72, 77- 81, 83-91 as lacking adequate written description on this basis. c) “drying to a dry, solid form by lyophilization” We agree with Appellant that the application as originally filed adequately described “a composition formed by drying to a dry, solid form by lyophilization.” The Examiner asserts that the limitation was not adequately described in the Specification at the time the application was filed because: (1) “[t]here is no verbatim support for this claim language”; (2) “[i]t does not appear that the formula exemplified in the specification as filed was lyophilized such that the final form in the example could be relied upon for possible support of this claim limitation”; and (3) it is not clear that all possible intermediate compositions of lipid structures as claimed would inherently lyophilize to a solid, dry product as required by claim 91.” Id. 5. Appeal 2021-002524 Application 11/616,658 13 We are not persuaded. “[T]he claimed subject matter need not be described in haec verba in the specification in order for that specification to satisfy the description requirement.” In re Smith, 481 F.2d 910, 914 (CCPA 1973). The Specification teaches drying the delivery composition by lyophilization. Spec. ¶ 70. The ordinary meaning of “lyophilization” is “[t]he process of isolating a solid substance from solution by freezing the solution and vaporizing the ice away under vacuum conditions.: freeze- drying.”11 Accordingly, we conclude that the Specification conveys with reasonably clarity to those skilled in the art that, as of the filing date of the application, Appellant was in possession of “a composition formed by drying to a dry, solid form by lyophilization,” which is all that is required for adequate written description. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). B. Indefiniteness (64, 72, 77-81, and 83-91) 1. Issue As discussed above, all the independent claims on appeal (claims 84, 90, 91) contains the following limitation: “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization.” Appeal Br. 54, 57, 59; see also Ans. 6. The Examiner concludes: The term “similar” in claims 84, 90 and 91 is a relative term which renders the claim indefinite. The term “similar” is not defined by the claim, the [S]pecification 11 See, e.g., “lyophilization.” DICTIONARY.COM, https://www.dictionary.com/browse/lyophilization (last visited Feb. 23, 2022) (emphasis added). Appeal 2021-002524 Application 11/616,658 14 does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The metes and bounds of this limitation cannot be determined and therefore the claim is indefinite as this limitation allows for some change in the distribution but neither the claims nor the [S]pecification indicate how much of a change is required for the distribution to no longer be similar. Ans. 6. Appellant contends that its arguments with respect to written description, above, also show that a skilled artisan “can ascertain the scope of the claim” with respect to the limitation “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization.” Appeal Br. 50. The issue with respect to this rejection is whether, in the context of the claims, a skilled artisan would have understood the metes and bounds of the limitation, “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization.” 2. Analysis “A claim is indefinite if its legal scope is not clear enough that a person of ordinary skill in the art could determine whether a particular composition infringes or not.” Geneva Pharms., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1384 (Fed. Cir. 2003). Likewise, “if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.” Ex parte Miyazaki, 2008 WL 5105055, at *5 (BPAI 2008) (precedential). Finally, “when the USPTO Appeal 2021-002524 Application 11/616,658 15 has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).” In re Packard, 751 F.3d 1307, 1311 (Fed. Cir. 2014). Consistent with the legal principles set forth above, we agree with the Examiner that the limitation, “wherein the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization,” is indefinite. In particular, a skilled artisan would not be able to determine whether a systemic delivery composition that otherwise meets the limitations of claim 84 would, upon reconstitution with water, have a size distribution of particles and vesicles sufficiently “similar” to that found prior to lyophilization so as to infringe the claim. Appellant relies on the same arguments it made with respect to the written description rejection. More particularly, Appellant first contends that the paragraphs 70-71 of its Specification, reproduced above, “teaches preserving the size [of the lipid aggregates] to an extent recognized as acceptable in the art.” Appeal Br. 48. Appellant then contends that the art “provides a basis for determining if a size distribution that is similar to that found prior to lyophilization,” because Katinger, Tardi, and Schmidt together teach that size of lipid vesicles and particles are important to maintain their biological effect and that “a 21% increase [in liposome size] may be acceptable, while a 25% increase is not.” Id. As an initial matter, we note that the fact “some claim language may not be precise . . . does not automatically render a claim invalid.” Seattle Appeal 2021-002524 Application 11/616,658 16 Box Co. v. Indus. Crating & Packaging, Inc., 731 F.2d 818, 826, 221 USPQ 568, 574 (Fed. Cir. 1984). Likewise, “whether the claims do, in fact, set out and circumscribe a particular area with a reasonable degree of precision and particularity” must be determined “not in a vacuum, but always in light of the teachings of the prior art and of the particular application disclosure as it would be interpreted by one possessing the ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232, 1235 (C.C.P.A. 1971). Nevertheless, we are not persuaded by Appellant’s arguments. As discussed above, Appellant relies only on attorney arguments rather than evidence to support its apparent contention that a skilled artisan in the art would understand a “similar” distribution of particle and vesicle size upon reconstitution to mean an increase in particle and vesicle size that is “acceptable.” However, “[a]ttorneys’ argument is no substitute for evidence.” Johnston, 885 F.2d at 1581. Neither does Appellant distinguish between a change in particle sizes, versus a change in the “distribution” of particle and vesicle sizes. Assuming for the sake of argument that a skilled artisan would understand a “similar” distribution of particle and vesicle size to mean an “acceptable” increase, Appellant also fails to show persuasively that such an artisan would be able to determine the metes and bounds of what would be an “acceptable” increase in particle or vesicle size upon reconstitution. First, Appellant fails to provide persuasive evidence that the teachings of Tardi and Schmidt are representative of what the art would consider as “acceptable” increases in liposome size upon reconstitution for all systemic delivery compositions. Johnston, 885 F.2d at 1581 (explaining that attorney arguments are not evidence). Appeal 2021-002524 Application 11/616,658 17 Appellant also contends that Tardi teaches that “somewhere less than 20 mol% is where cholesterol causes trouble” and that Tardi’s Figure 6A shows that “20% [cholesterol] yields a 25% increase in liposome size.” Appeal Br. 48. However, Tardi teaches that, if its liposomes are to be frozen, “it is preferred, but not required, that the liposomes be substantially free of cholesterol” - where “substantially no cholesterol” is described as “typically less than 20 mol % cholesterol” - “and comprise hydrophilic polymer lipid conjugates, particularly those greater than about 125 daltons as those liposomes are resistant to fusion and leakage of agent subsequent to freezing.” Tardi ¶¶ 19, 47 (emphasis added). Thus, it is not clear that Tardi would consider liposomes comprising greater than 20% cholesterol, and the alleged attendant increases in liposome size upon reconstitution (i.e., 25%), to be “unacceptable.”12 Likewise, Appellant does not provide persuasive evidence, or even cogent explanation, as to how Schmidt’s Table III shows that Tardi found “a 21% size increase (from control) to be acceptable . . . while a 36% increase . . . was not.”13 Appeal Br. 48. 12 Indeed, Tardi’s Figure 6A shows that a liposome comprising 0 mol % cholesterol had a > 25% increase in liposome size when thawing to room temperature after being frozen at -20° C. for 24 hours. Tardi Fig. 6A. 13 Appellant may have intended to argue that Schmidt’s Table III shows that Schmidt found “a 21% size increase (from control) to be acceptable . . . while a 36% increase . . . was not.” Even assuming Schmidt teaches what Appellant alleges, for the other reasons stated in this opinion, Appellant still does not show persuasively that a skilled artisan would be able to determine the metes and bounds of what would constitute a systemic delivery composition wherein “the size of the particles and vesicles reconstitutes to a distribution similar to that found prior to lyophilization.” Appeal 2021-002524 Application 11/616,658 18 Accordingly, for the reasons discussed above, we affirm the Examiner’s rejection of claims 64, 72, 77-81, and 83-91 as indefinite. C. Obviousness rejections Having found Appellant’s claims indefinite, we reverse, pro forma, the prior art rejections on this record. See Ex parte Miyazaki, 89 USPQ2d 1207, 1217-18 (BPAI 2008) (precedential) (prior art rejections of indefinite claims reversed by Board “pro forma” where claim interpretation required resort to “speculative assumptions as to the meaning of the claims”); see also accord, In re Steele, 305 F.2d 859, 863 (CCPA 1962).14 CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 64, 72, 77-81, 83-91 112, first paragraph Written description 64, 72, 77-81, 83-91 64, 72, 77-81, 83-91 112, second paragraph Indefiniteness 64, 72, 77-81, 83-91 64, 72, 77-80, 84, 85, 87, 88, 90, 91 103 Sköld, Yoshioka, Choi, Katinger, Schmidt 64, 72, 77-80, 84, 85, 87, 88, 90, 91 14 The decision to reverse pro forma is based solely on the indefiniteness of the claimed subject matter and does not address the merits of the evidence applied in support of the prior art rejections. Should prosecution resume and the 35 U.S.C. § 112 issues are resolved, Examiner should consider whether the prior art rejections are applicable as presented on this record or with other prior art. Appeal 2021-002524 Application 11/616,658 19 Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 81, 83, 86, 89 103 Sköld, Yoshioka, Choi, Katinger, Schmidt, Scott 81, 83, 86, 89 64, 72, 77-80, 84, 85, 87, 88, 90, 91 103 Sköld, Yoshioka, Choi, Katinger, Schmidt, Özer 64, 72, 77-80, 84, 85, 87, 88, 90, 91 81, 83, 86, 89 103 Sköld, Yoshioka, Choi, Katinger, Schmidt, Özer, Scott 81, 83, 86, 89 Overall Outcome 64, 72, 77-81, 83-91 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