Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I (i.e., claims 50-60 drawn to a method for preventing or reducing the binding by pre-existing antibodies to a heavy-chain immunoglobulin single variable domain or a polypeptide) in the reply filed on January 16, 2024, is acknowledged. Moreover, Applicant’s election of Species A (i.e., a single and specific heavy-chain immunoglobulin single variable domain with a N-glycosylation site at position 108) in the reply filed on January 16, 2024, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note that in light of the search results, Species B is expanded to position 14.
Status of Claims
Claims 1-37 were originally filed on March 17, 2022.
The amendment received on June 28, 2022, canceled claims 1-37; and added new claims 38-63. The amendment received on July 24, 2024, amended claims 50 and 60. The amendment received on February 14, 2025, canceled claim 63; amended claim 60; and added new claim 64. The amendment received on October 2, 2025, amended claims 38-40 and 50-52. The amendment received on April 22, 2026, canceled claims 38-49, 51, and 53-58; amended claims 50, 52, and 64; and added new claims 65-66. The amendment received on August 14, 2026, canceled claim 66.
Claims 50, 52, 59-60, and 64-65 are currently pending and are under consideration.
Priority
The present application is a continuation of US Application No. 15/554,744, filed on August 31, 2017, which claims status as a 371 (National Stage) of PCT/EP2016/055947 filed March 18, 2016, and claims priority under 119(e) to U.S. Provisional Application No. 62/135,968 filed on March 20, 2015.
Maintained/Modified Rejections in light of Applicants’ Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 50, 52, 59-60, and 64-65 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. Please note that the rejection has been updated in light of Applicants’ amendments; namely, cancellation of claim 66. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 50 includes a “heavy-chain immunoglobulin single variable domain Hc-(ISVD) or a polypeptide comprising the Hc-ISVD that consists of formula I: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 and an N-glycosylation site introduced at position 108”. As such, the required structure of the Hc-ISVD or polypeptide comprising the same includes a specific modification at the amino acid corresponding to position 108 according to Kabat numbering along with requiring each of the four FR domains and each of the three CDR domains. In addition to certain structural features, the Hc-ISVD or polypeptide comprising the same must also function such that binding by pre-existing antibodies to the glycosylated modified Hc-ISVD or glycosylated modified polypeptide is reduced by at least 25% (see instant claim 50) or at least 50% (see instant claim 65) relative to the amount of binding to the HC-ISVD or the polypeptide lacking the N-glycosylation site. As such, the reducing binding percentages ranges from 25% up to 100% and 50% up to 100%. Thus, the claimed invention correlates the presence of a N-glycosylation site at position 108 in the Hc-ISVD or polypeptide amino acid sequence with the reduced binding to pre-existing antibodies relative to a non-modified Hc-ISVD or polypeptide amino acid sequence.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Ashman et al. teaches modified proteins and peptides that have reduced ability to bind to pre-existing antibodies where the modified protein/peptide can comprise C-terminal additions, extensions or tags and/or certain amino acid substitutions (See Ashman et al. WO 2013/024059 A2 published (February 21, 2013) at pg. 1, 1st paragraph; pg. 3, 2nd paragraph). Such modified protein/peptide molecules including fusions thereof can comprise antigen binding molecules such as single variable domains, e.g., human HC-ISVDs and those derived from non-human sources such as llama or camel, e.g., VHH including a Nanobody™ (See Ashman specification, pg. 1, 1st paragraph; pg. 3, 2nd paragraph; pg. 5, 6th paragraph). Regarding the dAb and substitutions within the dAb, Ashman et al. teaches that the dAb monovalently binds to a target antigen and comprises (a) three CDR regions specific for the target antigen, (b) four framework (FR) regions, (c) a C-terminal sequence consisting of the sequence VTVS(S)nX or VEIKpRqX, and optionally (d) one or more amino acid substitutions at positions 14, 41, 108, 110 or 112 compared to a human germline framework sequence where n is 0 or 1, p and q each represent 0 or 1 such that when p represents 1, q may be 0 or 1, and when p represents 0, q also represents 0; and X may or may not be present, and if present represents 1 to 8 amino acid residues (See Ashman specification, pg. 4, 3rd paragraph). Furthermore, Ashman et al. teaches that the one or more substitutions can be selected from a P14A, P14K, P14Q, P14T, P41A, L108A, L108Q, T110A, and S112A substitution (See Ashman specification, pg. 5, 5th paragraph; pg. 19, 2nd-3rd paragraph). However, Ashman et al. does not teach where the one or more substitutions at position 108 result in a N-glycosylation site where such substitution results in reduced binding by pre-existing antibodies by at least 25% or at least 50% relative to the amount of binding to the Hc-ISVD or the polypeptide lacking the N-glycosylation site. Thus, the claims are directed to Hc-ISVDs or polypeptide comprising the same with a certain function but no indication what structure is necessary in order to achieve higher than 75% reduced binding (i.e., the claimed percentage ranges include 100%). Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification teaches in Example 2 that a polypeptide sequence comprising an introduced glycosylation site at position 108 (i.e., L108N), there is a reduction in pre-existing binding by 73% compared to the non-glycosylated polypeptide sequence of SEQ ID NO: 99 or to the comparative sequence of SEQ ID NO: 101 (See instant, Example 2). As such, the instant specification provides a specific species that has a specific sequence and specific introduced N-glycosylation site at position 108 that did not exceed 73% reduced binding. In other words, the specific species is not representative of the claimed functional genus because there is no indication what core structure is needed in order to achieve higher than 75% reduced binding by pre-existing antibodies. Thus, the specification is not sufficient for the skilled artisan to envisage Hc-ISVDs or polypeptide sequences that comprise an introduced N-glycosylation site at position 108 such that the full scope of the claimed function will be preserved.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 50, 52, 59-60, and 64-65 do not meet the written description requirement.
Response to Arguments
Applicant's arguments filed 8/14/26 for claims 50, 52, 59-60, and 64-65 as failing the written description requirement have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s first argument, i.e., since the written description requirement focuses on whether the Specification demonstrates that the inventors were in possession of the claimed invention and not individual subspecies (or subgenera) encompassed by the claimed invention, the claims recite adequate structure to achieve at least 25% or at least 50% reduced binding by pre-existing antibodies because a greater than 73% reduced binding by pre-existing antibodies is not a requirement recited in any of the pending claims (See Applicant’s Response received on 8//14/26, pg. 5), it is found unpersuasive. Pursuant to MPEP 2111, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1).
As discussed in the rejection supra, the scope of claims 50 and 65 encompass a reduced binding percent range. More specifically, claim 50 encompasses where the modified Hc-(ISVD) or a polypeptide comprising the Hc-ISVD reduce binding by pre-existing antibodies by a percentage of at least 25%, and claim 65 encompasses where the percentage is of at least 50%. The broadest reasonable interpretation of these claimed percent ranges is where the reduced binding by pre-existing antibodies is from 25% up to 100% or from 50% up to 100%. Thus, the scope of each claim encompasses reduced binding of any percentage within the claimed ranges.
Furthermore, MPEP 2163(II)(A)(1) states,
claim construction is an essential part of the examination process. Each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description. See, e.g., In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1319-1320, 97 USPQ2d 1737, 1750 (Fed. Cir. 2011). The entire claim must be considered, including the preamble language and the transitional phrase. The claim as a whole, including all limitations found in the preamble (see Pac-Tec Inc. v. Amerace Corp., 903 F.2d 796, 801, 14 USPQ2d 1871, 1876 (Fed. Cir. 1990) (determining that preamble language that constitutes a structural limitation is actually part of the claimed invention)), the transitional phrase, and the body of the claim, must be sufficiently supported to satisfy the written description requirement. An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations. Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
As such, although the claimed percent ranges do not require that the reduced binding is above 73%, compliance with the written description requirement is not limited to required limitations. Rather, written description compliance is evaluated in light of the broadest reasonable interpretation of the claim scope. Since the scope of claims 50 and 65 encompass a percent range, written description compliance is evaluated with respect to the entire range. Therefore, contrary to Applicant’s argument, the fact that the claimed invention does not require above 73% reduced binding by pre-existing antibodies does not preclude written description compliance of the broadest reasonable interpretation of the claimed ranges.
Moreover, it is acknowledged that the written description requirement does not require Applicants to demonstrate possession of every individual species of a claimed genus/subgenus. However, the written description requirement can be met either by demonstrating a core structure/sequence necessary for each species to exhibit a claimed function OR a representative number of species that fall within the claimed genus/subgenus. MPEP §2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Additionally, the importance of structure/function correlations was highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, App. No. 2013-1338, -1346 (Fed. Cir., July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the 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.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, Abbvie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the ’128 and ’485 patents do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.”
In the instant case, without an indication of a core structure, sequence or residues that would be necessary in order for the modified Hc-(ISVD) or a polypeptide comprising the Hc-ISVD to function in reducing binding by pre-existing antibodies by a percentage of at least 25% or at least 50%, it would be difficult for a skilled artisan to envision the correlation between structure and function for the whole genera and/or to predict what would be covered by the functionally claimed genera because Applicants have failed to provide a representative number of species to support the scope of the whole genera.
Similarly, MPEP 2163.05(I)(B), [t]he written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.) Here, although there are situations where a single species adequately supports a genus (See MPEP 2163.05(I)(B), e.g., In re Rasmussen, 650 F.2d 1212, 1214, 211 USPQ 323, 326-27 (CCPA 1981) (disclosure of a single method of adheringly applying one layer to another was sufficient to support a generic claim to "adheringly applying" because one skilled in the art reading the specification would understand that it is unimportant how the layers are adhered, so long as they are adhered), given that there is only one specific species (i.e., a modified HC-IVSD with a specific amino acid sequence) demonstrating a specific percentage of reduced binding by pre-existing antibodies, the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed. Therefore, given the breadth of the structure of the claimed modified HC-ISVD and breadth of the functional language, the Examiner maintains that the single species described in the specification cannot constitute a representative number of species within the claimed genera to constitute possession of the claimed genera.
In response to Applicant’s second argument, i.e., the specification teaches additional modifications, beyond introducing a glycosylation site at position 108, that can be made to a HC-ISVD to further reduce binding by pre-existing antibodies, and thus, one of ordinary skill in the art would reasonably conclude in view of the specification that the inventors were in possession of the claimed subject matter (See Applicant’s Response received on 8/14/26, pg. 5-6), it is found unpersuasive. Although it is acknowledged that the specification teaches additional modifications that could be made to the claimed HC-ISVD, the prior art and/or instant specification fail to establish a structure/function correlation between any of the additional modifications and reduced binding by pre-existing antibodies. Moreover, even if the additional modifications provide support for reduced binding by pre-existing antibodies by at least 25%, such additional modification(s) may then be considered a necessary structural limitation that the claimed invention must recite in order to satisfy the written description requirement. In other words, as an example, if the instant specification demonstrates that an additional added glycosylation site at position 14 results in the modified HC-ISVD exhibiting 85% reduced binding by pre-existing antibodies, then the additional structural feature at position 14 would be a required core structural limitation that the claimed invention would need to recite. Therefore, contrary to Applicant’s argument, the additional modifications taught in the specification do not allow one of ordinary skill in the art to reasonably conclude that the inventors were in possession of the claimed subject matter.
Accordingly, the rejection of claims 50, 52, 59-60, and 64-65 is maintained as Applicants’ arguments are found unpersuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 50, 52, 59-60, and 64-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,306,139 B2 (Buyse et al.) (cited in the IDS received on 6/28/22). Please note that the rejection has been updated in light of Applicants’ amendments; namely, cancellation of claim 66. Although the claims at issue are not identical, they are not patentably distinct from each other because Buyse et al. claims:
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(See ‘139 claims 1-3, 17, 19, 21, and 38-42 thereby corresponding to issued claims 1-3, 11-13, 17, 21-24). Thus, the ‘139 claimed HC-ISVD encompasses the instantly claimed HC-ISVD. However, ‘139 does not claim that the HC-ISVD reduces the binding by pre-existing antibodies by at least 25% or at least 50% relative to the amount of binding to a Hc-ISVD or polypeptide lacking the N-glycosylation site.
Regarding the instantly claimed use and where the method further comprises expressing, in glycosylated form, the HC-ISVD and measuring binding by pre-existing antibodies to the glycosylated form, pursuant to MPEP 804, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). Thus, even though the instant claims recite specificities not explicitly recited by the claims of the reference application, disclosed utilities of the instant claims encompassed by the claims of the reference application are disclosed in the specification of the reference application, and thus the instant claims are not patentably distinct from the claims of the reference application. In the instant case, ‘139 teaches that the present invention aims to provide a technique for reducing the binding of pre-existing antibodies to ISVDs by suitably introducing at least one glycosylation site into the same such that in the resulting Ig (single) variable domain, polypeptide, protein, compound, construct or other chemical entity, the at least one glycosylation site is glycosylated (See ‘139 specification, col. 3, 4th paragraph; col. 6, last paragraph to col. 7, 3rd paragraph) thereby constituting where the ‘139 claimed HC-ISVDs are used in a method of reducing the binding by pre-existing antibodies to HC-ISVDs by introducing at least one glycosylation site as recited in instant claim 50. ‘139 also teaches introducing one or more codons that encode a glycosylation site into a nucleotide sequence that encodes an Ig (single) variable domain, where the nucleotide can then be expressed in a suitable host cell or host organism to provide the Ig (single) variable domain om glycosylated form (See ‘139 specification, col. 3, 2nd to 3rd paragraph) thereby constituting expressing, in a glycosylated form, the HC-ISVD or the polypeptide comprising the same as recited in instant claim 64. Moreover, ‘139 teaches that a reduction of binding by pre-existing antibodies is calculated by the method described in Example 3 based on binding data obtained for a set of relevant serum samples, which binding data is measured for each sample and comparing it to a suitable reference (See ‘139 specification, col. 17, 3rd paragraph; col. 29-30, Example 3) thereby constituting measuring binding by pre-existing antibodies to the glycosylated form as recited in instant claim 64.
Regarding the instantly claimed functional property, i.e., percentage of reduced binding by pre-existing antibodies, since ‘139 claims the instant Hc-ISVD or polypeptide comprising the same and the ‘139 specification teaches that the Hc-ISVD or polypeptide comprising the same reduces binding by pre-existing antibodies, the functional property (i.e., at least 25% or at least 50% reduced binding by pre-existing antibodies relative to the amount of binding to the Hc-ISVD or the polypeptide lacking the N-glycosylation site) of the modified Hc-ISVD or modified polypeptide as claimed and the ‘139 modified Hc-ISVD or modified polypeptide. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new functional properties (i.e., at least 25% or at least 50% reduced binding by pre-existing antibodies relative to the amount of binding to the Hc-ISVD or the polypeptide lacking the N-glycosylation site) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977).
Therefore, the ‘139 claimed invention is not patentably indistinct from the instantly claimed invention.
Applicants’ Arguments
Applicants state that Applicant will consider filing a terminal disclaimer once the claims are otherwise in condition for allowance (See Applicants Response received on 8/14/26, pg. 6).
Response to Arguments
Applicant’s statement that filing a terminal disclaimer once the claims are otherwise in condition for allowance will be considered is acknowledged. As such, the double-patenting rejection is maintained.
Examiner Comment
Notwithstanding the 112(a) and nonobviousness-type double patenting rejections supra, the Examiner would like to note that the claimed invention is free of the prior art. There is no teaching or suggestion in the art to modify a Hc-ISVD sequence at position 108 such that it results in at least 25% reduced binding by pre-existing antibodies relative to the amount of binding to the Hc-ISVD or polypeptide lacking the N-glycosylation site. The closest prior art is Ashman et al. WO 2013/024059 A2 published (February 21, 2013) (cited in the Action mailed on 4/24/24). Ashman et al. teaches modified proteins and peptides that have reduced ability to bind to pre-existing antibodies where the modified protein/peptide can comprise C-terminal additions, extensions or tags and/or certain amino acid substitutions (See Ashman, pg. 1, 1st paragraph; pg. 3, 2nd paragraph). Such modified protein/peptide molecules including fusions thereof can comprise antigen binding molecules such as single variable domains, e.g., human HC-ISVDs and those derived from non-human sources such as llama or camel, e.g., VHH including a Nanobody™ (See Ashman specification, pg. 1, 1st paragraph; pg. 3, 2nd paragraph; pg. 5, 6th paragraph). Regarding the dAb and substitutions within the dAb, Ashman et al. teaches that the dAb monovalently binds to a target antigen and comprises (a) three CDR regions specific for the target antigen, (b) four framework (FR) regions, (c) a C-terminal sequence consisting of the sequence VTVS(S)nX or VEIKpRqX, and optionally (d) one or more amino acid substitutions at positions 14, 41, 108, 110 or 112 compared to a human germline framework sequence where n is 0 or 1, p and q each represent 0 or 1 such that when p represents 1, q may be 0 or 1, and when p represents 0, q also represents 0; and X may or may not be present, and if present represents 1 to 8 amino acid residues (See Ashman specification, pg. 4, 3rd paragraph). Furthermore, Ashman et al. teaches that the one or more substitutions can be selected from a P14A, P14K, P14Q, P14T, P41A, L108A, L108Q, T110A, and S112A substitution (See Ashman specification, pg. 5, 5th paragraph; pg. 19, 2nd-3rd paragraph). However, an L108Q substitution can reduce binding by pre-existing antibodies by about 9% and a L108A substitution can reduce binding by pre-existing antibodies by about 5% (See Ashman, Tables 1 and 3). Thus, the instantly claimed invention is free of the prior art.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached on M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Examiner, Art Unit 1654
