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 .
Election/Restrictions
Applicant’s election without traverse of the species: K536, inhibition of reduction of induced TNFalpha shedding; SEQ ID NO: 22 and 27 (VH/VL) and SEQ ID NO: 23, 24, 25, 28, 29, 30 (CDRs), clone #16; and inflammatory condition, in the reply filed on 23 December 2024 is acknowledged.
Claims 1-16 are examined upon their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/EP2022/058301 filed on 29 March 2022, and claiming the benefit of European Patent Application Nos. EP21181135.1 filed on 23 June 2021 and EP21165604.6 filed on 39 March 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claims 1-16 have an earliest effective US filing date of 39 March 2021.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 11/07/2023; 12/23/2024; 05/29/2025; and 06/12/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the words “means for” (claims 1-3, 5, 7-15). These claims are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) fail to recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: means for binding to human iRhom2 (claims 1-3, 5 and 7-15).
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
Claim Rejections - 35 USC § 112
Claim 10 and 11 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 10 and 11 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: there appears to be no structural similarity within the sequences encoding for CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3; nor among VH and VL sequences.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “inhibiting or reducing” in claims 1 and 13-15 is a relative term which renders the claim indefinite. The terms “inhibiting” and “reducing” are not defined by the claims, nor does the specification provide a standard for ascertaining the requisite degree. Further, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention, because there are no active, positive steps for determining said inhibition or reduction. Thus, a person having ordinary skill would not know whether or not assessing an inhibition or reduction was required for infringement. Absent active steps, then this recitation is directed to an intended effect and these claims will be interpreted as anticipated by administering, to a human or animal subject, any means for binding to human iRhom2 which binds at least within a region of Loop 1, wherein the means for binding to human iRhom2 comprises a protein binder, or of a nucleic acid that encodes for at least one chain of a protein binder. This affects the scope of all depending claims.
Claim 2 is indefinite wherein it recites parenthetical phrases because it is unclear whether the limitations following the phrase are part of the claimed invention.
Claim 4 is similarly indefinite wherein it recites, “wherein the inhibition or reduction of TACE/ADAM17 activity is caused by interference with iRhom2-mediated TACE/ADAM17 activation.” This further limits the inhibition or reduction for which there is no active step in the first place. Absent method steps, it is unclear how these claims further limit the scope of the parent claim. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since the claim fails to meet all (3) criteria set forth in MPEP 2173.05(g), then the claim is rejected.
Claims 14-15 are vague and indefinite in so far as it employs the term "clone #16" as a limitation. This term appears to be novel, and without a reference to a precise amino acid sequence identified by a proper SEQ ID NO: one cannot determine the metes and bounds of “clone #16”. Moreover, because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of “clone #16”, an artisan cannot determine if a compound which meets all of the other limitations would then be included or excluded from the claimed subject matter by the presence of this limitation.
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 1-16 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claims 1-3, 5, 7-9, and 12-15 recites “means for binding to human iRhom2”. The claims do not require that the “means for binding” possess any particular structure or other distinguishing feature and therefore the claims are drawn to a genus of binding molecules. Claims 7-8 and 14-15 recite an antibody but fail to specify and particular antibody structure.
The Federal Circuit (Federal Circuit) decided in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), that disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
Further the instant claims encompass antibodies: that bind to amino acid sequences having only 80% identity with the sequence of iRhom2 (claim 6); antibodies that have “at least one of the CDRs has a sequence identity of 66%” to the CDR sequences (claim 10); antibodies that have 80% identity to the HCVD OR LCVD sequences (claim 11); and, antibodies that “target binding affinity of 50% to human iRhom2” OR “50% of the inhibiting or reducing effect on TACE/ADAM17” (claim 13). In view of the Amgen decision, the instant claims fail to meet the requirements for disclosure because the antibody is described solely by the antigen to which it binds.
In Amgen the court stated, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites.
MPEP 2163(II)(3)(a)(i)(A) states: 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 (, reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a) (i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Therefore, in view of the current case law, Claims 1-16 are rejected since they fail to provide all 6 CDR structures.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods comprising administering the instantly-elected clone #16 consisting of SEQ ID NO: 22 and 27 (VH/VL) and SEQ ID NO: 23, 24, 25, 28, 29, 30 (CDRs), does not reasonably provide enablement for administering any other antibody nor for treating or preventing any inflammatory condition, autoimmune disease or neoplastic disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
The case law applies to the instant claims which read upon methods comprising any “means for binding to human iRhom2”, yet the inventors have disclosed the amino acid sequences of only 13 discrete antibodies.
In Amgen, the Supreme Court has stated:
“An antibody’s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.’ Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody’s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody’s structure and function. Ibid.”
Given that structure is essential to function; and given that the Supreme Court concedes that much unpredictability remains within the art with respect to creating antibodies, then a person having ordinary skill in the art would have to perform further experimentation in order to make the full scope of antibodies encompassed by the claims. Given the nature of the invention, a skilled artisan would have to make multiple “means for binding to human iRhom2” and use them in methods comprising in vivo administration in order to enable the invention commensurate in scope with the breadth of the claims. This amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
For all of these reasons, the specification does not enable the claims, and Claims 1-16 are rejected under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-9 are rejected under 35 U.S.C. 102(a)(1), or in the alternative 102(a)(2), as being anticipated by WO/2020/208150 published 9 April 2020 (hereafter WO ‘150).
Regarding claim 1, the WO ‘150 prior art teaches an antibody that binds to human iRhom2, specifically within recognize an epitope within the section of the large extracellular loop 1 of human iRhom2 (Figure 4). Table 1 of the reference defines Loop 1 of iRhom2 as covering amino acids 474 through 600 of SEQ ID NO:16 of the reference, which is identical to SEQ ID NO: 181 of the instant claims (see alignment below). The reference discloses administering said antibody to a patient throughout and discloses said antibody is “capable to bind to human iRhom2 with sufficient binding affinity and to inhibit or reduce TACE/ADAM17 activity”. Thus, the prior art anticipates a method for inhibiting or reducing TACE/ADAM17 activity in a human or animal subject which comprises administering to the human an effective amount for reducing or inhibiting TACE/ADAM 17 TACE/ADAM17 activity of a means for binding to human iRhom2 which, when bound to human iRhom2, binds at least within a region of Loop 1 thereof.
Regarding claims 2 and 3, the prior art teaches anti-iRhom2 antibodies that bind within the Loop 1, which it defines as residues 474-600, means for binding to human iRhom2. Thus, the prior art teaches an means for binding iRhom2, that binds within at least a region of human iRhom2 spanning from W526 to 1566 that the instant application defines as Loop 1. This necessarily encompasses residues W526; Q527; P532; P533; M534; D535; K536; S537; L539; K542; R543; T544; G546; R554; E557; S561; S562 and/or 1566, as defined by instant claim 3.
Regarding claims 4 and 5, the prior art teaches the antibody of the prior art is “sufficient binding affinity and to inhibit or reduce TACE/ADAM17 activity”. Therefore, the prior art teaches inhibition or reduction of TACE/ADAM17 activity, which claim 5 necessarily defines as inhibition or reduction of induced TNFa shedding and/or inhibition or reduction of induced IL-6R shedding, and/or inhibition or reduction of induced HB-EGF shedding. Further, the prior art teaches “TACE-mediated release of tumor necrosis factor alpha (TNFa) from macrophages is very well established” and the antibody blocks LPS-induced TNFa shedding in THP-1 cells. Therefore, the prior art teaches reduction of TNFa shedding.
Regarding claim 6, the prior art teaches an antibody the that is raised against the identical amino acid sequence set forth in SEQ ID NO 181. See alignment below.
Regarding claim 7 and 8, the prior art teaches an antibody that binds human iRhom2 is a monoclonal antibody, and defines “monoclonal antibody (mAb)” shall refer to an antibody composition having a homogenous antibody population, i.e., a homogeneous population consisting of a whole immunoglobulin, or a fragment or derivative thereof retaining target binding capacities. Particularly preferred, such antibody is selected from the group consisting of IgG. Therefore, the prior art teaches monoclonal and the format of IgG.
Regarding claim 9, the prior art teaches an antibody that does not cross reactive with human iRhom1.
PNG
media_image1.png
1028
800
media_image1.png
Greyscale
Therefore, the invention of Claims 1-9 fails to distinguish over what was disclosed in the prior art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/STACEY N MACFARLANE/ Examiner, Art Unit 1675
Prosecution Insights