DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 29, 2026 has been entered.
Application Status
The amended claims filed on June 29, 2026 with the Request for Continued Examination are acknowledged. Claims 32 and 40-43 are amended.
Claims 30-46 are pending and under examination herein.
Priority
This application is a U.S. national phase application of International Application No. PCT/EP2020/060179, which was filed on April 9, 2020, and claims priority to European Application No. 19168218.6, filed on April 9, 2019, and European Patent Application 19209426.6, filed November 15, 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 on October 7, 2021.
The earliest support for the subject matter of claims 30-36 and 45-46 is found in European Application No. 19168218.6, filed on April 9, 2019.
The earliest support for the subject matter of claims 37-44 is found in European Patent Application 19209426.6, filed November 15, 2019.
WITHDRAWN OBJECTIONS AND REJECTIONS
The objection to the Drawings is withdrawn in view of Applicant's amendments to the Brief Description of the Drawings on pages 3-4.
The objection of claim 32 is withdrawn in view of Applicant's amendments to the claim.
The provisional rejection of claims 30 and 34-36 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-8, and 21-22 of co-pending Application No. 17/764,819 further in view of Issuree (US 2015/0241429 A1; cited in PTO-892 mailed January 28, 2025) is withdrawn in view of Applicant's amendments to the co-pending claims.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 112(a)
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 30-36 and 45-46 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. 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection has been updated to reflect Applicant's amendments to the claims.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
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 it may be satisfied by the 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. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[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.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017) supported previous decisions (Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification. See also pages 206-208 of Deng (mAbs (2018) 10(2): 204-209; cited in IDS).
The claimed invention. The nature and scope of the claimed invention at issue is a method for inhibiting and/or reducing TACE/ADAM17 activity in a subject, the method comprising administering to the subject an antibody or fragment thereof that specifically binds to the juxtamembrane domain adjacent to the transmembrane domain 1 (TMD1) of human iRhom2 (as recited in claim 30 and its dependent claims). This limitation fails to satisfy the written description requirement because the antibody or fragment thereof administered in the instantly claimed method is defined by its functional attributes (i.e., binding to a specific epitope of human iRhom2) without reciting a corresponding structure expected to correlate with said function. Claims 31-36 and 45-46, which depend from claim 30, do not remedy these written description issues raised by the independent claim.
Claim 31 further sets forth that administration of the antibody or fragment thereof of claim 30 inhibits or reduces TNF-α shedding. The claim further defines the antibody by its functional properties, without reciting a specific structure (e.g., amino acid sequence) expected to correlate with the specifically claimed functions.
Claim 32 further sets forth that the juxtamembrane domain comprises an amino acid [sic] corresponding to residues 431-459 of SEQ ID NO: 16, and claim 33 recites that the epitope bound by the antibody or fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 3. These claims continue to further define the epitope bound by the antibody administered in the instantly claimed method, without reciting a corresponding structure expected to perform the function of binding to said epitope.
Of note, claims 37- 39 (which recite a complete combination of three heavy chain CDR and three light chain CDR amino acid sequences) and claim 44 (which recites a complete combination of VH and VL amino acid sequences, inclusive of their respective CDRs) recite a sufficient level of structure expected to correlate with the instantly claimed function of binding to a juxtamembrane domain of the TMD1 of human iRhom2 based on Applicant’s disclosure, and are not included in this rejection.
State of the prior art. It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751; cited in PTO-892 mailed January 28, 2025) at “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302; cited in PTO-892 mailed January 28, 2025) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3, left column, “CDRs Identification”).
Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni (The Protein Journal (2024) 43: 683-696; cited in PTO-892 mailed January 28, 2025) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (Almagro et al., pages 3 and 6-7).
Gershoni (Biodrugs (2007) 21(3): 145-156; cited in PTO-892 mailed January 28, 2025) teaches that antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (page 146, Section 1.1). The skilled artisan therefore understands that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence. Further, the state of the art recognizes that it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes, that are dictated by the unique interaction between an antibody and its cognate epitope (Blythe, Protein Science (2005) 14:246-248, at page 246; cited in PTO-892 mailed January 28, 2025).
With respect to iRhom2, Siggs (Immunobiology (2012) 119(24): 5769-5771; cited in IDS) teaches that iRhom2 may be an attractive target for inflammatory diseases in view of its role in the secretion of TNF-α, a proinflammatory cytokine synthesized in response to activation of Toll-like receptor (TLR) signaling pathway (page 5769). Exemplary antibodies to iRhom2 (also known as “RHBDL5” and “RHBDL6”) are described by Bicknell (WO 2009/044158 A2; cited in PTO-892 mailed January 28, 2025), Issuree (US 2015/0241429 A1; cited in IDS), and Blobel (US 10,024,844 B2; cited in PTO-892 mailed January 28, 2025).
Scope of species disclosed in original specification. The working examples discuss the generation of iRhom2 immunization peptides and screening for anti-iRhom2 activity-neutralizing antibodies, wherein iRhom2-knockout mice were immunized with human iRhom2 peptide mixes and hybridoma cells were generated from the resulting splenic lymphocytes (Examples 1-5; Figure 1). A single supernatant collected from the hybridoma cell population “4H8” interfered with LPS-induced TNF-α shedding in THP-1 cells (Example 5). The oligoclonal “4H8” clone was expanded, and three monoclonal subclones (4H8-D4, 4H8-E3, and 4H8-G8) were determined to interfere with TNF-α shedding and further expanded (Example 6).
The purified antibody subclone 4H8-E3 was determined to be of mouse IgM isotype (Examples 7-8; Figure 3). Antibody 4H8-E3 binds to an epitope localized within amino acids 431 to 459 of the extracellular juxtamembrane domain of human iRhom2 (Example 9; Figure 4) and does not bind to related family member human iRhom1 (Example 10; Figure 5). Purified antibody 4H8-E3 was determined to inhibit LPS-induced release of TNF-α from THP-1 cells by 62.6% (Example 11; Figure 6).
The antibody 4H8-E3 clone comprises VH and VL CDRs comprising SEQ ID NO: 34-36, respectively, and SEQ ID NO: 41-43, respectively (as determined with the Paratome CDR Identification tool, which is no longer publicly available), or VH and VL CDRs comprising SEQ ID NO: 37-39, respectively, and SEQ ID NO: 44-46, respectively (as determined with in-house methods), and VH and VL sequences comprising the amino acid sequences of SEQ ID NO: 33 and 40, respectively (pages 15 and 42).
The structures (i.e., amino acid sequences) and epitopes of the remaining antibody subclones (i.e., 4H8-D4 and 4H8-G8) described in the working examples are not disclosed.
MPEP § 2163 states that 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. Although three antibody subclones of the 4H8 hybridoma have been recited in the disclosure, only one subclone (4H8-E3, a murine IgM antibody) is described with sufficient particularity such that the skilled artisan could recognize its structure and how this structure correlates with its functional properties of binding to a specific epitope within residues 431-459 of the extracellular juxtamembrane domain of human iRhom2 and interfering with TNF-α shedding. The antigen-binding structure of additional antibody clones that bind to the same epitope as antibody subclone 4H8-E3 is not described in the disclosure.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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. As illustrated by the state of the art, the CDR structures in the VH and VL of conventional antibodies are a critical determinant of functional antigen-binding properties. As recited above, the structure of only one antibody subclone, 4H8-E3, has been described in the disclosure with sufficient detail to satisfy the written description requirement. The disclosure does not provide guidance with respect to which residue(s) within any of the six CDRs of the antibody subclone may be modified while still retaining the claimed functional properties. As such, further testing would be required for the skilled artisan to be able to determine which residues may be substituted while retaining specific binding for the claimed epitopes.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless other anti-human iRhom2 antibodies encompassed by the highly general structural requirements of the claims would also possess the required functional activity of binding specifically to the juxtamembrane domain adjacent to the transmembrane domain 1 (TMD1) of human iRhom2 and inhibiting and/or reducing the activity of TACE/ADAM17. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of anti-human iRhom2 antibodies that specifically bind to the juxtamembrane domain adjacent to the transmembrane domain 1 and inhibit and/or reduce the activity of TACE/ADAM17 as broadly claimed at the time the application was filed.
Response to Arguments
Applicant's arguments filed June 29, 2026 have been fully considered but they are not persuasive.
Applicant argues that the recent precedential decision by the Federal Circuit Authority, Teva Pharmaceuticals International GmbH v. Eli Lilly and Company, No. 2024-1094 (Fed. Cir. April 16, 2026), hereafter “Teva” (cited in Office Action Appendix), “makes clear that novel antibody genus composition claims and method-of-use claims are evaluated under materially different standards. The court’s analysis squarely holds that the demanding ‘representative number of species’ / ‘structural features common to members of the genus’ framework … does not apply with equal force when the genus at issue is not itself the invention but rather a component of a different claimed invention”. Remarks at page 7. Applicant submits that, as in Teva, the instant claims are drawn to a therapeutic use of the antibody, as opposed to the antibody itself. Applicant further submits that “A skilled artisan reading the specification would understand that an antibody binding the juxtamembrane domain (residues 431-459 of SEQ ID NO: 16) adjacent to TMD1 would interfere with iRhom2-mediated TACE/ADAM17 activation, thereby accomplishing the claimed method”. Remarks at pages 7-8.
In response, it is held that the fact pattern and corresponding analysis described in Teva for “the headache patents” are materially distinct from that of the instant application and claims. For reference, the representative claim at issue in Teva was directed to “A method for reducing incidence of or treating headache in a human, comprising administering to the human an effective amount of an anti-CGRP antagonist antibody, wherein said anti-CGRP antagonist antibody is a . . . humanized monoclonal antibody.” Teva at pages 3-4. With respect to the instantly claimed invention, the independent claim at issue is drawn to “A method for inhibiting and/or reducing TACE/ADAM17 activity in a subject, the method comprising administering to the subject an antibody or fragment thereof specifically binding to the juxtamembrane domain adjacent to the transmembrane domain 1 (TMD1) of human iRhom2”. It is also noted that the written description requirement takes into consideration not only the content of the Applicant's disclosure but also the level of skill and knowledge in the art as well as the predictability of the art at the time of filing of the instantly claimed invention. See MPEP §§ 2161 and 2163.
The analysis in Teva notes that the disclosures of the headache patents cited prior art demonstrating that anti-CGRP antagonist antibodies were ‘known in the art’ and also disclosed prior art methods for humanizing antibodies. Teva at page 13. Importantly, the Teva decision also recites, “Although the specification disclosed just one humanized anti-CGRP antagonist antibody, it also disclosed several murine versions and prior-art methods of humanization—against a backdrop of anti-CGRP antagonist antibodies (and methods of making them) being well known and humanization being routine. And, critically, a skilled artisan would have understood from the specification that all humanized anti-CGRP antagonist antibodies treat headache” (emphasis added). Teva at page 13. Applying this thought pattern to the instantly claimed invention, a pertinent question to ask is, “Would the skilled artisan have understood from Applicant's specification that all antibodies that specifically bind to the juxtamembrane domain adjacent to TMD1 of human iRhom2 inhibit and/or reduce TACE/ADAM17 activity? Based on Applicant's disclosure and the state and predictability of the prior art at the time of filing, it is held that the answer to this question is no.
Regarding the teachings of Applicant's disclosure, Applicant sets forth that 5280 peptide immunization-derived hybridoma supernatants were generated from mice immunized with a peptide mix A, B, or C, where Mix A consisted of equal amounts of peptides 1, 2, 3, and 4, with peptide 3 corresponding to the peptide with an amino acid sequence of SEQ ID NO: 3, corresponding to residues 431-459 of human iRhom2 (Examples 3-5; Figure 1). Applicants screened the 5280 supernatants for their iRhom2 activity-neutralizing properties by using an ELISA-based functional screen to compare LPS-induced release of endogenous TNF-α from human THP-1 macrophages in the presence and absence of said supernatants (Example 5). Applicant states, “Of the 5280 hybridoma supernatants tested in total, the supernatant collected from the hybridoma cell population of plate number 4, row H, column 8, (4H8) is the only one clearly interfering with LPS-induced TNFα shedding in THP-1 cells” (Example 5; emphasis added). See also Figure 2 of Applicant's Drawings. Based on these observations, the skilled artisan – in contrast to Applicant's assertions – would not have reasonably understood that an antibody that specifically binds to juxtamembrane domain (residues 431-459 of SEQ ID NO: 16) adjacent to TMD1 would also interfere with iRhom2-mediated TACE/ADAM17 activation, given that a single species of antibody out of the more than 5000 analyzed by Applicant possessed both of these functional attributes as presently claimed.
Regarding the state and predictability of the relevant art herein, the following excerpt from the Supreme Court’s decision in Amgen, Inc. et al. v. Sanofi et al., No. 21-757, Decided May 18, 2023), at page 3, is highlighted here:
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A search of the prior art suggests that the genus of antibodies that specifically bind to iRhom2 at any epitope was generally less well-characterized than, e.g., anti-CGRP antibodies, at the time of filing of the instantly claimed invention. The genus of antibodies that specifically bind to the epitope corresponding to residues 431-459 of human iRhom2 (corresponding to the amino acid sequence set forth in instant SEQ ID NO: 3) appears to be even less well-characterized. While Bicknell (WO 2009/044158 A2; supra) describes methods of use of an iRhom2 inhibitor, where the iRhom2 inhibitor may be an antibody among others, Bicknell does not expressly describe the epitope bound by such an antibody and does not teach that such an antibody would inhibit or reduce TACE/ADAM17 activity. Issuree (US 2015/0241429 A1; supra) teaches an antibody or antigen-binding fragment thereof that binds to the extracellular loop of human iRhom2 (e.g., NP 078875.4, which corresponds to instant SEQ ID NO: 16; see page 40 of Applicant's disclosure), decreases the biological activity of iRhom2 and modulates formation of a complex between iRhom2 and TACE (e.g., ¶ 0006-0007; 0027; 0036-0037; 0058; 0060-0061). Issuree teaches that in preferred embodiments, the anti-iRhom2 antibody recognizes the amino acid sequence of “GPSDKSDLSQKQPSAVVCHQDPRTCEEPASSGAHIWPDDITKWPICTEQAQS” in the extracellular loop of iRhom2 (e.g., ¶ 0037), which shares 86.3% local similarity to residues 533-583 of the human iRhom2 sequence recited in instant SEQ ID NO: 16. The anti-iRhom2 antibodies set forth by Blobel (U.S. Patent No. 10,024,844; supra), which also inhibit the activity of TACE, are similarly described as binding an extracellular domain of iRhom2 (e.g., the same epitope “GPS…AQS” set forth by Issuree), a transmembrane region, or an epitope including both (e.g., col 11, lines 12-31). Applicant's disclosure does not expressly recite additional examples of anti-iRhom2 antibodies known in the prior art which possess the functional activity of binding to the juxtamembrane domain adjacent to TMD1 of human iRhom2 and/or inhibiting or reducing the activity of TACE/ADAM17. Based on this understanding of the state and predictability of the art at the time the instantly invention was filed, the skilled artisan would have understood that (1) the claimed genus of antibodies set forth in the instant claims is not a well-known genus (unlike in Teva), and (2) not all antibodies which bind to the juxtamembrane domain adjacent to TMD1 of human iRhom2 would also be expected to possess the required functional activity of inhibiting and/or reducing the activity of TACE/ADAM17 as presently claimed.
For at least these reasons, the rejection is maintained.
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.
(1)
Claims 30-32, 34-36, and 45-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-22 and 24-38 of co-pending Application No. 17/764,819 (reference application ‘819; cited in PTO-892 mailed January 28, 2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention. This rejection has been updated to reflect amendments to the instant and co-pending claims.
Regarding claims 30-31 and 46, co-pending claims 21-22 and 29-30 recite a method for treating an inflammatory condition in a subject that comprises administering to the subject an antibody or fragment thereof that binds at least within a region of Loop 1 thereof of human iRhom2 spanning residues 474-660, inhibits and/or reduces TACE/ADAM17 activity when bound to human iRhom2, and reduces or inhibits induced TNF-α shedding. Pertinent to claim 34, co-pending claim 26 recites that the fragment is a scFv, Fab, or (Fab)2. Pertinent to claims 35-36, co-pending claims 27-28 recite that the antibody has an IgG or IgM isotype and is a murine antibody, chimeric antibody, humanized antibody, or human antibody. Co-pending claim 38 recites that the subject is human, relevant to claim 45.
As evidenced by the instant specification, the residues spanning positions 431-459 of human iRhom2 correspond to the juxtamembrane domain section of the large extracellular loop 1 of human iRhom2, adjacent to TMD1 (page 3; Figure 8), relevant to claim 32. Thus, the epitope recited in the instant claims is within the scope of “within a region of Loop 1” of human iRhom2 recited in the co-pending claims.
(2)
Claims 30-32, 34-36, and 45-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-15, and 17-20 of co-pending Application No. 18/279,715 (reference application ‘715). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention. This is a new rejection.
The ‘715 reference application recites a method of treating an inflammatory condition, comprising administering to a human or animal subject an antibody or fragment thereof of co-pending claim 1, which is a humanized anti-iRhom2 antibody that inhibits or reduces TACE/ADAM17 activity, binds at least within a region of Loop 1 of human iRhom2, and inhibits or reduces induced TNF-α shedding (co-pending claims 1, 8-10, 19), relevant to claims 30-31, 36, and 45-46. Co-pending claim 13 recites that the antibody is IgG, scFv, Fab, or (Fab)2, relevant to claims 34-35.
As evidenced by the instant specification, the residues spanning positions 431-459 of human iRhom2 correspond to the juxtamembrane domain section of the large extracellular loop 1 of human iRhom2, adjacent to TMD1 (page 3; Figure 8), relevant to claim 32. Thus, the epitope recited in the instant claims is within the scope of “within a region of Loop 1” of human iRhom2 recited in the co-pending claims.
(3)
Claims 30-32, 34-36, and 45-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of co-pending Application No. 18/284,782 (reference application ‘782; cited in PTO-892 mailed January 28, 2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention.
Regarding claims 30-32 and 45-46, co-pending claims 1, 5-6, and 16 recite a method for treating or preventing an inflammatory condition, comprising administering to a human subject an effective amount of a means for binding, comprising a protein binder, that binds at least within a region of Loop 1 of human iRhom2 (SEQ ID NO: 181, which shares 100% identity to instant SEQ ID NO: 16). Said means for binding inhibits or reduces TACE/ADAM17 activity and inhibits or reduces TNF-α shedding. Co-pending claim 4 recites that the inhibition or reduction of TACE/ADAM17 activity is caused by interference with iRhom2-mediated TACE/ADAM17 activation. Co-pending claims 7-8 recite that the means for binding is a monoclonal antibody or target-binding fragment thereof, and that the antibody is selected from IgG, scFv, Fab, or (Fab)2, relevant to claims 34-35. Co-pending claims 13-15 further recite methods comprising administering an effective amount of a means for binding to human iRhom2 to a human subject for reducing or inhibiting TACE/ADAM17 activity.
Co-pending claims 10-11 recite that the means for binding iRhom2 is an antibody comprising a combination of heavy chain and light chain CDRs and/or a combination of a heavy chain variable region (VH) and a light chain variable region (VL). As evidenced by the Examples of the co-pending disclosure, said antibodies were generated in mice and are therefore murine and/or humanized antibodies, anticipating claim 36.
As evidenced by the instant specification, the residues spanning positions 431-459 of human iRhom2 correspond to the juxtamembrane domain section of the large extracellular loop 1 of human iRhom2, adjacent to TMD1 (page 3; Figure 8), relevant to claim 32. Thus, the epitope recited in the instant claims is within the scope of “within a region of Loop 1” of human iRhom2 recited in the co-pending claims.
Response to Arguments
Applicant's arguments filed June 29, 2026 have been fully considered but they are not persuasive.
Applicant submits that the ‘819 and ‘782 applications have later patent term filing dates than the instant application, and that since “all other grounds of rejection have been properly traversed, accommodated, or rendered moot”, withdrawal of the provisional non-statutory double patenting rejections is requested.
In response, it is held that the other grounds of rejection have not been traversed for the reasons set forth above. Accordingly, the provisional non-statutory double patenting rejections are maintained.
Allowable Subject Matter
Claims 37-44 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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