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 .
Claim Status
Claims 1-20 are pending and presently subject to a restriction/election requirement. Claims 12-15 and 17-20 are withdrawn. Claims 1-11 and 16 are presently examined.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-14, 16 as filed 8/07/2023) and the species of SEQ ID NO: 29 in the reply filed on 8/25/2025 is acknowledged.
The traversal is on the grounds that Unity of Invention exists because all groups share 80% sequence identity with SEQ ID NOs: 16-35 (see, e.g., Reply filed 8/25/2025 at 2-3). This is not found persuasive because this is not a special technical feature as it does not make a contribution over the prior art in view of US20150299265A1 (cited in previous action), which teaches and discloses SEQ ID NO: 114, which shares 85% sequence identity with instant SEQ ID NO: 16, and has three mutations relative to SEQ ID NO: 39 (i.e., 87.88% identity) (compare instant SEQ ID NO: 16 and 39 with US’265 at SEQ ID NO: 114). It is the Examiner’s understanding that Applicant generally traverses the teachings of US’265 on the grounds that it does not disclose specific features or functional descriptions, or the originally elected species (see, e.g., Reply filed 8/25/2025 at 2-3). The elected species is not the identified common special technical feature shared among the groups (see, e.g., Reply filed 8/25/2025 at 2, noting that 80% sequence identity with any one of SEQ ID NOs: 16-35 is the shared feature); accordingly, such argument does not establish unity of invention. Furthermore, arguments pertaining to unclaimed features do not distinguish the claimed invention. In addition, arguments directed to features and functional descriptions fail to actually identify how the exact prior art structure of US’265 is excluded from the scope of the pending claims. Accordingly, the traversal is not persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 15 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/25/2025.
The originally elected species is understood to be SEQ ID NO: 29, which has the structure of
GSDLGKKLLQAARAGQLDEVRELLKAGADVNAKDTWGFTPLHIAAESGHLEIVEVLLKAGADVNAKDVQGRTPLHIAAHSGHLEIVEVLLKAGADVNAKDFRGWTPLHLAAWSGHLEIVEILLKAGADVNAQDKSGKTPADLAARAGHQDIAEVLQKAA
The originally elected species of SEQ ID NO: 29 is understood to comprise instant SEQ ID NO: 76 (KDTWGFTPLHIAAESGHLEIVEVLLKAGADVNA);instant SEQ ID NO: 77 (KDVQGRTPLHIAAHSGHLEIVEVLLKAGADVNA); instant SEQ ID NO: 78 (KDFRGWTPLHLAAWSGHLEIVEILLKAGADVNA); instant SEQ ID NO: 5 (GSDLGKKLLQAARAGQLDEVRELLKAGADVNA); and instant SEQ ID NO: 13 (QDKSGKTPADLAARAGHQDIAEVLQKAA).
Accordingly, the elected species is understood to read upon claims 1-11 and 16. However, claims 12-14 were not indicated as reading upon the originally elected species; Claims 12-13 require a second “ankyrin repeat domain” beyond SEQ ID NO: 29, and therefore does not read upon the originally elected species. Claim 14 requires a “localizer molecule”, which was not identified as present in the originally elected species. Claim 7 is understood to be the broadest claim on record1.
Following extensive search and examination, the originally elected species of SEQ ID NO: 29 was deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was then extended to a non-elected species, namely a species of recombinant binding protein comprising an ankyrin repeat domain having at least 80% amino acid sequence identity with SEQ ID NO: 29, namely
GSDLGKKLLEAARAGQDDEVRILLKAGADVNAKDRYGDTPLHLAADIGHLEIVEVLLKAGADVNAEDYFGNTPLHLAASYGHLEIVEVLLKAGADVNAKDDYGNTPLHLAANTGHLEIVEVLLKAGADVNAQDKSGKTPADLAADAGHEDIAEVLQKAA
Following extensive search and examination, such sequence was deemed anticipated in view of the prior art (see, e.g., Rejection in view of SEQ ID NO: 60 from patent US 9458211, below).
The non-elected species is understood to read upon instant claims 1-7, 10-11, and 16 are rejected. As a courtesy to Applicant, claims 8-9 are examined although they do not read upon the non-elected species.
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 1-11 and 16 are presently considered.
Priority
The priority claim to EP20174830.8 (filed 5/14/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 11/14/2022 is acknowledged and presently considered.
Examiner notes that the IDS failed to identify relevant US Patent Applications and Patent filings disclosing or claiming overlapping subject matter.
Specification
Sequence Listing: The instant disclosure is objected to for not complying with 37 C.F.R. 1.821 as detailed in MPEP §§ 2421–2424. Specifically, the instant application does not comply with 37 C.F.R. 1.821(b)-(e). The instant claims and/or disclosure contain references or disclosures of amino acid sequences that should be accompanied by a sequence listing and identified using "SEQ ID NOs” as prescribed (see MPEP §§ 2421–2424). Specifically, the instant application discloses sequences at page 39 at lines 6-10 of the Substitute Specification (Marked) filed 8/07/2025.
Appropriate correction is required.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claims 1 and 7 are representative of the pending claim scope and presently recites, wherein claim 7 is understood to be representative of the claimed invention2. The applicable claim interpretation is set forth below.
Regarding the preamble of claims 1 and 7 (i.e., “A recombinant binding protein comprising an ankyrin repeat domain”), per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claims 1 and 7 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”). More specifically, at claim 7, the preamble is deemed fully satisfied by any protein comprising an amino acid sequence sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing. At claim 1, the preamble is deemed fully satisfied by any protein “comprising an amino acid sequence selected from the group consisting of” SEQ ID NOs: 39-95 or “sequences in which up to 10 amino acids in any of SEQ ID NOs: 39 to 95 are substituted by other amino acids”.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)).
“CD40” is understood to not refer to a specific polypeptide, but instead is used to “refer to any form of CD40 receptor, as well as to variants, isoforms, and species homologs thereof that retain at least a part of the activity of CD40 receptor. . . . CD40 includes all mammalian species of native sequence CD40, e.g., human, canine, feline, equine and bovine” (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40). Accordingly, the term “CD40” is used as an Applicant-defined genus that refers to myriad sequences, including “variants, isoforms, and species homologs” of unknown structure (see id).
Regarding the clause stating “wherein said ankyrin repeat domain has binding specificity for CD40” at claims 1 and 7: The “wherein” clause has been rejected as indefinite for reasons set forth below in a rejection under 35 USC 112(b). For purposes of applying prior art, in the absence of a corresponding and unambiguous structure/function relationship, the “wherein” clauses are interpreted as a recitation of an intended or expected result, fully satisfied by all polypeptides satisfying the positively recited structural limitations set forth in the body of each claim (see, e.g., MPEP § 2111.04(I), “[c]laim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”).
Regarding claim 10 and the “wherein” clause reciting “wherein said ankyrin repeat domain binds human CD40 in PBS with a dissociation constant (KD) below 10-7 M”: The “wherein” clause has been rejected as indefinite for reasons set forth below in a rejection under 35 USC 112(b). For purposes of applying prior art, in the absence of a corresponding and unambiguous structure/function relationship, the “wherein” clauses are interpreted as a recitation of an intended or expected result, fully satisfied by all polypeptides satisfying the positively recited structural limitations set forth in the body of claim 7 (see, e.g., MPEP § 2111.04(I), “[c]laim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”).
Claim 11 recites the “wherein” clause “wherein said ankyrin repeat domain specifically binds to the N-terminal cysteine-rich domain 1 (CRD1) (amino acids 23-59 of SEQ ID NO: 96) of the CD40 receptor”: The “wherein” clause has been rejected as indefinite for reasons set forth below in a rejection under 35 USC 112(b). For purposes of applying prior art, in the absence of a corresponding and unambiguous structure/function relationship, the “wherein” clauses are interpreted as a recitation of an intended or expected result, fully satisfied by all polypeptides satisfying the positively recited structural limitations set forth in the body of claim 7 (see, e.g., MPEP § 2111.04(I), “[c]laim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”).
Additional claim interpretations are set forth below.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
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 1-8, 10-11, and 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.
Claim 1 recites a “wherein” clause reciting “wherein said ankyrin repeat domain has binding specificity for CD40”, which renders the claim scope indefinite because it is unclear (i) if the “wherein” clause is a recitation of an intended or expected results fully satisfied by all structures satisfying the positively recited structural limitations set forth in the body of the claim3 (i.e., non-limiting), or (ii) if the “wherein” clause is a functional limitation that further narrows the scope of claimed compounds beyond those that satisfy the positively recited structural limitations set forth in the body of the claim 4, as alleged by the Applicant (see, e.g., Reply filed 8/25/2025 at 2-3, alleging “functional differences”). The difference in scope between these two interpretations is vast: Each of SEQ ID NOs: 39-95 are all 33 amino acids in length, and therefore “up to 10” amino acid substitutions reads upon 23/33 identities, or 69.59% sequence identity with each of 57 different amino acid sequences, which is >1910 (i.e., over 6 trillion possibilities per sequence); however, if the “wherein” clause is a functional limitation, then it may only read upon instant SEQ ID NOs: 39-95 (i.e., 57 non-variable sequences). Accordingly, the difference in interpretations potentially varies in multiple orders of magnitude. The difference in scope between these two interpretations impacts identification of prior art: Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). If the “wherein” clause is a functional limitation, it is unclear if such prior art sequences read upon the instant claims or not; therefore, an artisan would not be reasonably informed of the boundaries of what constitutes infringement of such claims as required by 35 USC § 112(b) (see, e.g., MPEP § 2173). Accordingly, the difference in potential interpretations renders the claim scope indefinite. For purposes of applying prior art under 35 USC § 102 or § 103, per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”. Accordingly, because the “wherein” clause does not correspond to any unambiguous structure/function relationship of record5, the “wherein” clause is reasonably understood to be a recitation of intended and expected results for purposes of applying prior art, satisfied by all prior art sequences that satisfy the positively recited structural limitations set forth in the body of the claim. Specifically, for purposes of applying prior art, claim 1 is deemed fully satisfied by any protein “comprising an amino acid sequence selected from the group consisting of” SEQ ID NOs: 39-95 or “sequences in which up to 10 amino acids in any of SEQ ID NOs: 39 to 95 are substituted by other amino acids”.
Claim 7 recites a “wherein” clause reciting “wherein said ankyrin repeat domain has binding specificity for CD40”, which renders the claim scope indefinite because it is unclear (i) if the “wherein” clause is a recitation of an intended or expected results fully satisfied by all structures satisfying the positively recited structural limitations set forth in the body of the claim6 (i.e., non-limiting), or (ii) if the “wherein” clause is a functional limitation that further narrows the scope of claimed compounds beyond those that satisfy the positively recited structural limitations set forth in the body of the claim 7, as alleged by the Applicant (see, e.g., Reply filed 8/25/2025 at 2-3, alleging “functional differences”). The difference in scope between these two interpretations is vast: Each of SEQ ID NOs: 16 to 35 are either 126 or 159 amino acids in length, and therefore “80%” sequence identity means 25 substitutions in 126-mers and 31 substitutions in 159-mers; this means that for each of SEQ ID NOs: 16-35 (i.e., 20 sequences), claim 7 may presently encompass >>1925 possibilities (i.e., >>9.3 x1031 possibilities per sequence). However, if the “wherein” clause is a functional limitation, then the scope of the claim is unknown, but may only read upon instant SEQ ID NOs: 16-35 (i.e., 20 non-variable sequences). Accordingly, the difference in interpretations potentially varies in multiple orders of magnitude. The difference in scope between these two interpretations impacts identification of prior art: Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). If the “wherein” clause is a functional limitation, it is unclear if such prior art sequences read upon the instant claims or not; therefore, an artisan would not be reasonably informed of the boundaries of what constitutes infringement of such claims as required by 35 USC § 112(b) (see, e.g., MPEP § 2173). Accordingly, the difference in potential interpretations renders the claim scope indefinite. For purposes of applying prior art under 35 USC § 102 or § 103, per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”. Accordingly, because the “wherein” clause does not correspond to any unambiguous structure/function relationship of record8, for purposes of applying prior art, the “wherein” clause is reasonably understood to be a recitation of intended and expected results, satisfied by all prior art sequences that satisfy the positively recited structural limitations set forth in the body of the claim. Specifically, for purposes of applying prior art, claim 7 is deemed fully satisfied by any protein “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
Claims 1 and 7 each recite a “wherein” clause reciting “wherein said ankyrin repeat domain has binding specificity for CD40”, which has been deemed to render each claim indefinite for the reasons set forth in the two preceding paragraphs, which are incorporated herein. For purposes of the instant rejection, the “wherein” clause at claims 1 and 7 are understood to be directed to a functional limitation, which renders the scope of the claim indefinite as described below. If the “wherein” clause is a functional limitation, it is unclear how to apply or interpret the limitation: MPEP § 2173.05(g) identifies that functional limitations may be ambiguous and render a claim scope indefinite. Specifically, MPEP § 2173.05(g) explains that
A claim term is functional when it recites a feature "by what it does rather than by what it is"….
…..
Notwithstanding the permissible instances, 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. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008)…..
Here, the “wherein” clause fails to correspond to a structure/function limitation commensurate in scope with the claims. Therefore, it is unclear how an artisan would identify and distinguish infringing and non-infringing embodiments as required by as required by 35 USC § 112(b) (see, e.g., MPEP § 2173). The interpretation of the “wherein” clause alters the claim scope: The phrase “wherein said ankyrin repeat domain has binding specificity for CD40” is indefinite if interpreted as a functional limitation because “CD40” is defined as a genus rather than a single species (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40, noting that CD40 may “refer to any form of CD40 receptor, as well as to variants, isoforms, and species homologs thereof that retain at least a part of the activity of CD40 receptor. . . . CD40 includes all mammalian species of native sequence CD40, e.g., human, canine, feline, equine and bovine”). Accordingly, a basic question is whether or not the potential functional limitation requires “specific binding” to all species of CD40 (e.g., all “variants” and “homologs”) simultaneously, or if the “specific binding” limitation is satisfied so long as specific binding exists for a single species of CD40. This distinction changes the potential scope of the claim since under one interpretation a sequence capable of binding human CD40 with “specificity”, but not a “variant” of feline CD40 is excluded from the pending claim scope, but included under the alternative interpretation. Close prior art exists that satisfies all positively recited structural limitations set forth in the body of the claim(s): Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). Accordingly, even assuming arguendo that the “wherein” clause was a functional limitation, it would remain indefinite because it is unclear how to apply the “functional limitation” in a manner that reasonably permits an artisan to identify and distinguish among infringing and non-infringing embodiments as required by 35 USC § 112(b) (see, e.g., MPEP § 2173).
Claim 10 recites the “wherein” clause “wherein said ankyrin repeat domain binds human CD40 in PBS with a dissociation constant (KD) below 10-7 M”, which renders the claim scope indefinite because it is unclear (i) if the “wherein” clause is a recitation of an intended or expected results fully satisfied by all structures satisfying the positively recited structural limitations set forth in the body of claim 79 (i.e., non-limiting), or (ii) if the “wherein” clause is a functional limitation that further narrows the scope of claimed compounds at claim 7 beyond those that satisfy the positively recited structural limitations set forth in the body of claim 7 10, as suggested by the Applicant (see, e.g., Reply filed 8/25/2025 at 2-3, alleging “functional differences”). The difference in scope between these two interpretations is vast: Each of SEQ ID NOs: 16 to 35 are either 126 or 159 amino acids in length, and therefore “80%” sequence identity means 25 substitutions in 126-mers and 31 substitutions in 159-mers; this means that for each of SEQ ID NOs: 16-35 (i.e., 20 sequences), claim 7 may presently encompass >>1925 possibilities (i.e., >>9.3 x1031 possibilities per sequence). However, if the “wherein” clause at dependent claim 10 is a functional limitation, then it is prima facie unclear if claim 10 reads upon only instant SEQ ID NOs: 16-35 (i.e., 20 non-variable sequences), only SEQ ID NO: 29, or perhaps trillions of different sequences. Accordingly, the difference in interpretations potentially varies in multiple orders of magnitude since it is unclear how claim 10 further limits the scope of claim 7. The difference in scope between these two interpretations impacts identification of prior art: Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). If the “wherein” clause is a functional limitation, it is unclear if such prior art sequences read upon the instant claim 10 or not; therefore, an artisan would not be reasonably informed of the boundaries of what constitutes infringement of such claims as required by 35 USC § 112(b) (see, e.g., MPEP § 2173). The difference in interpretation impacts prosecution and examination of claim 10: Claim 10 is a dependent claim; therefore, if claim 10 is further limiting (i.e., the “wherein” clause is limiting, but in an unknown way) then a rejection under 35 USC § 112(a) is required. However, if the claim is not further limiting and merely recites an intended or expected result satisfied by all embodiments of claim 7, then claim 10 should be rejected under 35 USC § 112(d) for failing to further limit the scope of the claim upon which it depends. Accordingly, the difference in potential interpretations renders the claim scope indefinite. For purposes of applying prior art under 35 USC § 102 or § 103, per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”. Accordingly, because the “wherein” clause does not correspond to any unambiguous structure/function relationship of record, for purposes of applying prior art, the “wherein” clause is reasonably understood to be a recitation of intended and expected results, satisfied by all prior art sequences that satisfy the positively recited structural limitations set forth in the body of the independent claim. Specifically, for purposes of applying prior art, claims 10 and 7 are deemed fully satisfied by any protein “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
Claim 11 recites the “wherein” clause “wherein said ankyrin repeat domain specifically binds to the N-terminal cysteine-rich domain 1 (CRD1) (amino acids 23-59 of SEQ ID NO: 96) of the CD40 receptor”, which renders the claim scope indefinite because it is unclear (i) if the “wherein” clause is a recitation of an intended or expected results fully satisfied by all structures satisfying the positively recited structural limitations set forth in the body of claim 711 (i.e., non-limiting), or (ii) if the “wherein” clause is a functional limitation that further narrows the scope of claimed compounds at claim 7 beyond those that satisfy the positively recited structural limitations set forth in the body of claim 7 12, as suggested by the Applicant (see, e.g., Reply filed 8/25/2025 at 2-3, alleging “functional differences”). The difference in scope between these two interpretations is vast: Each of SEQ ID NOs: 16 to 35 are either 126 or 159 amino acids in length, and therefore “80%” sequence identity means 25 substitutions in 126-mers and 31 substitutions in 159-mers; this means that for each of SEQ ID NOs: 16-35 (i.e., 20 sequences), claim 7 may presently encompass >>1925 possibilities (i.e., >>9.3 x1031 possibilities per sequence). However, if the “wherein” clause at dependent claim 11 is a functional limitation, then it is prima facie unclear if claim 11 reads upon only instant SEQ ID NOs: 16-35 (i.e., 20 non-variable sequences), only SEQ ID NO: 29, or perhaps trillions of different sequences. Accordingly, the difference in interpretations potentially varies in multiple orders of magnitude since it is unclear how claim 11 further limits the scope of claim 7. The difference in scope between these two interpretations impacts identification of prior art: Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). If the “wherein” clause is a functional limitation, it is unclear if such prior art sequences read upon the instant claim 11 or not; therefore, an artisan would not be reasonably informed of the boundaries of what constitutes infringement of such claims as required by 35 USC § 112(b) (see, e.g., MPEP § 2173). The difference in interpretation impacts prosecution and examination of claim 11: Claim 11 is a dependent claim; therefore, if claim 11 is further limiting (i.e., the “wherein” clause is limiting, but in an unknown way) then a rejection under 35 USC § 112(a) is required. However, if the claim is not further limiting and merely recites an intended or expected result satisfied by all embodiments of claim 7, then claim 11 should be rejected under 35 USC § 112(d) for failing to further limit the scope of the claim upon which it depends. Accordingly, the difference in potential interpretations renders the claim scope indefinite. For purposes of applying prior art under 35 USC § 102 or § 103, per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”. Accordingly, because the “wherein” clause does not correspond to any unambiguous structure/function relationship of record, for purposes of applying prior art, the “wherein” clause is reasonably understood to be a recitation of intended and expected results, satisfied by all prior art sequences that satisfy the positively recited structural limitations set forth in the body of the independent claim. Specifically, for purposes of applying prior art, claims 11 and 7 are deemed fully satisfied by any protein “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
Claim 7 recites “an amino acid sequence with at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16 to 35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”, which renders the claim scope indefinite because it is unclear how to apply the optional limitation. This issue alters the scope of the pending claims: It is unclear if “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16 to 35” is considered before or after the “optional” removal of G at position 1 and S at position 2. This alters the pending claim scope because, for example, SEQ ID NO: 16 is 126-mer, and therefore “80%” sequence identity means 25 substitutions in 126-mers, which implies that the claim scope encompasses >>1925 possibilities. However, if “GS” at positions 1 and 2 are removed first, then SEQ ID NO: 16 becomes a 124-mer, therefore “80%” sequence identity means 24 substitutions in 124-mers, which implies that the claim scope encompasses fewer species, namely >>1924 possibilities. Accordingly, the order and timing of the “optional” removal substantially impacts the scope of the claim by approximately 19-fold per sequence. Close prior art exists: Close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). Accordingly, the difference in potential interpretations renders the claim scope indefinite since there exists more than one reasonable interpretation, and an artisan would not be reasonably apprised of what exact embodiments are included or excluded by the pending claim scope. For purposes of applying prior art under 35 USC § 102 or § 103, the “optional” limitations have not been considered in view of the prior art at this time.
Claims 8 and 9 each recites “…wherein G at position 1 and/or S at position 2 of said ankyrin repeat domain are optionally missing”, which renders the claim scope indefinite because there is insufficient antecedent basis for “G at position 1 and/or S at position 2 of said ankyrin repeat domain”. Here, “said ankyrin repeat domain” merely “comprises” the enumerated SEQ ID NO, and therefore “said ankyrin repeat domain” does not require a glycine at “position 1” or a serine at “position 2”, because no initial position is defined; stated alternatively, “said ankyrin repeat domain” does not “consist of” SEQ ID NO: 29 and need not begin with SEQ ID NO: 29 (e.g., position 1 and position 2 may correspond to proline in a leader sequence appended to the N-terminal of SEQ ID NO: 29). Accordingly, claims 8 and 9 are rejected as indefinite. For purposes of applying prior art, the phrase at claims 8 and 9 are understood to refer to SEQ ID NO: 29 rather than “said ankyrin repeat domain”.
Claims 2-6, 10-11, and 16 each depend directly or indirectly from an indefinite base claim, and fail to clarify the indefiniteness of the base claim. Accordingly, claims 2-6, 8, 10-11, and 16 are rejected as indefinite for the reasons applied to the base claim.
Accordingly, claims 1-11 and 16 are rejected as indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10-11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 10-11 each depend from independent claim 7 by the recitation of a “wherein” clause, which does not correspond to a structure/function relationship that unambiguously further limits the scope of claim 7 to a narrower set of claims (see, e.g., Rejections of claims 10-11 under 35 USC § 112(b), that discussion is incorporated into the instant rejection). In the absence of evidence that such “wherein” clauses further limit the scope of claim 7, such “wherein” clauses at dependent claims 10-11 are reasonably understood to merely be recitations of intended and expected results fully satisfied by all possible polypeptides that satisfy the positively recited functional limitations set forth in the body of independent claim 7 (i.e., any peptide that comprises “an amino acid sequence with at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16 to 35…). Accordingly, as recitations of intended or expected results fully satisfied by all embodiments of independent claim 7, the “wherein” clauses at claims 10-11 are reasonably understood to not further limit the scope of claim 7 (see, e.g., MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”). Accordingly, claims 10-11 are rejected under 35 U.S.C. § 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
If Applicant disagrees, Applicant may establish that claims 10-11 are further limiting by clearly identifying at least one embodiment within the scope of instant claim 7 that is excluded by the “wherein” clause recited at each of claims 10-11, supported by a functional limitation set forth in the originally filed disclosure.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a), Written Description
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 1-11 and 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) contain 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.
Brief Statement of the Issue(s)
For purposes of the instant claim scope, the “wherein” clauses at claims 1, 7, and 10-11, are understood to be functional limitations, which is reasonable in view of Applicant’s own statements (see, e.g., Reply filed 8/25/2025 at 2-3). The issue is that these “wherein” clauses do not correspond to a structure/function relationship on record, and therefore it is prima facie unclear how such limitations limit the claim scope.
Claim Scope
Claims 1 and 7 are representative of the pending claim scope. The claim scope is indefinite as discussed under 35 USC § 112(b), and those discussions are incorporated herein.
The scope of claim 1 is potentially vast and highly varied. Specifically, prior to consideration of the functional limitation, the positively recited structural limitations set forth in the body of the claim ostensibly encompasses >>trillions of species. Each of SEQ ID NOs: 39-95 are all 33 amino acids in length, and therefore “up to 10” amino acid substitutions reads upon 23/33 identities, or 69.59% sequence identity with each of 57 different amino acid sequences, which is >1910 (i.e., over 6 trillion possibilities per sequence). However, it is unclear if the “wherein” clause reciting “wherein said ankyrin repeat domain has binding specificity for CD40” limits the scope of claim 1 to a much smaller genus of functional sequences comprising perhaps only instant SEQ ID NOs: 39-95 (i.e., 57 non-variable sequences). Accordingly, claim 1 may read upon >>trillions of species or perhaps only 57 or fewer sequences.
The scope of claim 7 is potentially vast and highly varied. Specifically, the positively recited structural limitations set forth in the body of the claim, prior to consideration of the functional limitation, encompasses >>trillions of species. Each of SEQ ID NOs: 16 to 35 are either 126 or 159 amino acids in length, and therefore “80%” sequence identity means 25 substitutions in 126-mers and 31 substitutions in 159-mers; this means that for each of SEQ ID NOs: 16-35 (i.e., 20 sequences), claim 7 may presently encompass >>1925 possibilities (i.e., >>9.3 x1031 possibilities per sequence). However, it is unclear if the “wherein” clause reciting “wherein said ankyrin repeat domain has binding specificity for CD40” limits the scope of claim 7 to a much smaller genus of functional sequences comprising perhaps only instant SEQ ID NOs: 16 to 35 (i.e., 20 non-variable sequences). Accordingly, claim 7 may read upon >>trillions of species or perhaps only 57 or fewer sequences.
Accordingly, the pending claim scope is vast and highly varied, potentially reading upon >>trillions of sequences, or perhaps only a few dozen.
Actual Reduction to Practice
The originally filed disclosure discloses SEQ ID NOs: 16 to 35, which are identified as having “binding specificity for hCD40” (see, e.g., Spec. filed 8/07/2023 at 39 at lines 25-35), and SEQ ID NOs: 39 to 95 were identified as being “individual ankyrin repeat modules” that have “binding specificity for hCD40” (see, e.g., Spec. filed 8/07/2023 at 39 at lines 25-35, Table 1 on 41).
The originally filed disclosure discloses KD values for SEQ ID NOs: 22, 29, and 31 (see, e.g., Spec. filed 8/07/2023 at 42-43 at Table 2). It is unclear if SEQ ID NOs: 16-21, 23-28, 30, or 32-35 satisfy the limitation of claim 10.
The originally filed disclosure discloses a crystal structure for SEQ ID NO: 29 ((see, e.g., Spec. filed 8/07/2023 at 49 at lines 4-10, p. 51 at § Results, noting that SEQ ID NO: 29 is shown to bind to CRD1 of the CD40 receptor (i.e., amino acids 23-59)), corresponding to the functional limitation at instant claim 11. It is unclear if SEQ ID NOs: 16-28 or 30-35 satisfy the limitation of claim 11.
Zero species having less than 100% sequence identity to one of SEQ ID NOs: 16 to 35 or SEQ ID NOs: 39 to 95 were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species lacking G at position 1 or S at position 2 relative to SEQ ID NOs: 16 to 35 were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species of variants of SEQ ID NOs: 16 to 35 lacking “DIAEVLQKAA” at the C-terminus were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species of variants of SEQ ID NOs: 39-95 lacking the general conserved structure of
KD[KVSWRETAQHFI][HIEVFQWLKYRST]G[YRSQEWHVFLI]TPLH[IYSLWVH]A[AT][HLFKYRQEWNI][AHKERTYSQPV][GR][HS][LP]EIV[EG][VI]LLK[AVS]G[AE]DVNA
Wherein brackets show alternatives at a single residue. As noted, multiple positions are completely invariant or are shown to be only two possibilities, forming the general motif
KD..G.TPLH.A…[GR][HS][LP]EIV[EG][VI]LLK.G[AE]DVNA
(wherein “.” represents any amino acid). In addition, multiple variant positions appear not to be compatible with some amino acid residues (e.g., cysteine or proline), and multiple variants only appear in combination with other compensating variants (i.e., only instant SEQ ID NO: 74 lacks “GHLEIVE” and has “RSPEIVE” instead, therefore the “RS” substitution for “GH” only appears when both residues are altered together rather than separately and independently altered). Accordingly, zero species evidencing that all positions may be substituted to any amino acid, without limit, were reduced to practice, because all disclosed species share substantially conserved and limited motifs.
Zero species of “ankyrin repeat modules” or “ankyrin repeat domains” were taught, disclosed, or reduced to practice as having binding specificity to all CD40 proteins as presently claimed (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40, noting that “CD40” as claimed, is used to “refer to any form of CD40 receptor, as well as to variants, isoforms, and species homologs thereof that retain at least a part of the activity of CD40 receptor. . . . CD40 includes all mammalian species of native sequence CD40, e.g., human, canine, feline, equine and bovine”). Zero species of polypeptide were disclosed as having binding specificity to any “variant”, “isoform”, “species homologs”, canine CD40, feline CD40, equine CD40, or bovine CD40. Rather all species were shown to have only “binding specificity for hCD40” (see, e.g., Spec. filed 8/07/2023 at 39 at lines 25-35).
In sum, the originally filed disclosure disclosed 57 “ankyrin repeat modules” (i.e., SEQ ID NOs: 39-95), sharing substantial conserved motifs, and also disclosed 20 “ankyrin repeat domains” (i.e., SEQ ID NOs: 16-35), which also share the same substantial conserved motifs and additional conserved regions that appear to be non-variable (e.g., the C-terminal “DIAEVLQKAA”, etc.).
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Here, there is substantial variation within the genus as explained above, because the structural limitations of the pending claims encompass >>trillions of species of polypeptides, which may be varied at all positions, without limit, and without a required conservative motif beyond a minimum required sequence identity or maximum number of substitutions relative to SEQ ID NOs: 16-35 or SEQ ID NOs: 39-95.
Therefore, the relevant issue is whether or not the originally filed disclosure described a sufficient variety of species to reflect the variation within the claimed genus of ostensibly >>trillions of species. As noted above, in the instant disclosure reduces to practice:
Zero species having less than 100% sequence identity to one of SEQ ID NOs: 16 to 35 or SEQ ID NOs: 39 to 95 were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species lacking G at position 1 or S at position 2 relative to SEQ ID NOs: 16 to 35 were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species of variants of SEQ ID NOs: 16 to 35 lacking “DIAEVLQKAA” at the C-terminus were tested, reduced to practice, or shown to satisfy the recited functional limitations.
Zero species of variants of SEQ ID NOs: 39-95 lacking the general conserved structure of
KD[KVSWRETAQHFI][HIEVFQWLKYRST]G[YRSQEWHVFLI]TPLH[IYSLWVH]A[AT][HLFKYRQEWNI][AHKERTYSQPV][GR][HS][LP]EIV[EG][VI]LLK[AVS]G[AE]DVNA
Wherein brackets show alternatives at a single residue. As noted, multiple positions are completely invariant or are shown to be only two possibilities, forming the general motif
KD..G.TPLH.A…[GR][HS][LP]EIV[EG][VI]LLK.G[AE]DVNA
In addition, multiple variant positions appear not to be compatible with some amino acid residues (e.g., cysteine or proline), and multiple variants only appear in combination with other compensating variants (i.e., only instant SEQ ID NO: 74 lacks “GHLEIVE” and has “RSPEIVE” instead, therefore the “RS” substitution for “GH” only appears together rather than independently). Accordingly, zero species evidencing that all positions may be substituted to any amino acid, without limit, were reduced to practice, because all disclosed species share substantially conserved and limited motifs.
Zero species of “ankyrin repeat modules” or “ankyrin repeat domains” were taught, disclosed, or reduced to practice as having binding specificity to all CD40 proteins as presently claimed (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40, noting that “CD40” as claimed, is used to “refer to any form of CD40 receptor, as well as to variants, isoforms, and species homologs thereof that retain at least a part of the activity of CD40 receptor. . . . CD40 includes all mammalian species of native sequence CD40, e.g., human, canine, feline, equine and bovine”). Zero species of polypeptide were disclosed as having binding specificity to any “variant”, “isoform”, “species homologs”, canine CD40, feline CD40, equine CD40, or bovine CD40. Rather all species were shown to have only “binding specificity for hCD40” (see, e.g., Spec. filed 8/07/2023 at 39 at lines 25-35).
One species satisfying the functional limitation recited at instant claim 11 (see, e.g., Spec. filed 8/07/2023 at 49 at lines 4-10, p. 51 at § Results, noting that SEQ ID NO: 29 is shown to bind to CRD1 of the CD40 receptor (i.e., amino acids 23-59). It is therefore unclear whether or not the entire structure of SEQ ID NO: 29 is critical for binding, or if particular motifs within SEQ ID NO: 29 are required for binding or not. Zero variation in structure was demonstrated as satisfying this functional limitation.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of zero (or only one) species within a much vaster genus of the claimed invention does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Assuming that the “wherein” clauses in the pending claims are functional limitations, a basic threshold question, is “what exact species from among the trillions encompassed by the bodies of instant claims 1 and 7 are sufficient to satisfy the functional limitation requiring ‘wherein said ankyrin repeat domain has binding specificity for CD40’?” Unfortunately, no structure/function relationship commensurate in scope with instant claim 1 or 7 has been found on record reasonably informing an artisan of how to distinguish, a priori, species that are (or are not) excluded from the pending claim scope by this recitation. Rather, the Specification merely provides a laundry list disclosure of trillions of species, and appears to utilize the “wherein” clause to merely recite an intended and expected result the Applicant wants the invention to achieve, while leaving it to future researchers to actually discover which structures, from among >>trillions, are (or are not) included by the pending claims.
Assuming that the “wherein” clauses in the pending claims are functional limitations, a basic threshold question, is “what exact species from among the trillions encompassed by the bodies of instant claim 7 are sufficient to satisfy the functional limitation at dependent claim 10, requiring ‘wherein said ankyrin repeat domain binds human CD40 in PBS with a dissociation constant (KD) below 10-7 M’?” Unfortunately, no structure/function relationship commensurate in scope with instant claims 7 and 10 has been found on record reasonably informing an artisan of how to distinguish, a priori, species that are (or are not) excluded from the pending claim scope by this recitation. Rather, the Specification merely provides a laundry list disclosure of trillions of species and limited experimental evidence regarding only three highly similar sequences (see, e.g., Spec. filed 8/07/2023 at 42-43 at Table 2, disclosing KD values for only SEQ ID NOs: 22, 29, and 31). Accordingly, the Applicant is understood to utilize the “wherein” clause at claim 10 to merely recite an intended and expected result the Applicant wants the invention to achieve, while leaving it to future researchers to actually discover which exact structures, from among >>trillions, are (or are not) included by the pending claims.
Assuming that the “wherein” clauses in the pending claims are functional limitations, a basic threshold question, is “what exact species from among the trillions encompassed by the bodies of instant claim 7 are sufficient to satisfy the functional limitation at dependent claim 11, requiring "‘wherein said ankyrin repeat domain specifically binds to the N-terminal cysteine-rich domain 1 (CRD1) (amino acids 23-59 of SEQ ID NO: 96) of the CD40 receptor’?” Unfortunately, no structure/function relationship commensurate in scope with instant claims 7 and 11 has been found on record reasonably informing an artisan of how to distinguish, a priori, species that are (or are not) excluded from the pending claim scope by this recitation. Rather, the Specification merely provides a laundry list disclosure of trillions of species and limited experimental evidence regarding a single sequence (see, e.g., Spec. filed 8/07/2023 at 49 at lines 4-10, p. 51 at § Results, noting that SEQ ID NO: 29 is shown to bind to CRD1 of the CD40 receptor (i.e., amino acids 23-59). Accordingly, the Applicant is understood to utilize the “wherein” clause at claim 11 to merely recite an intended and expected result the Applicant wants the invention to achieve, while leaving it to future researchers to actually discover which exact structures, from among >>trillions, are (or are not) included by the pending claims.
In summary, the functional limitations set forth in claims 1, 7, and 10-11 are utilized as a recitation of an intended and expected result that Applicant hopes and desires that the disclosed invention is able to achieve. However, the disclosure but does not meaningfully disclose an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the functional limitations at issue. Accordingly, such recitations of a hoped-for and desired result does not place Applicant in possession of all embodiments exhibiting the hoped-for and desired results, since Applicant fails to meaningfully identify the structures that are actually required to achieve such hoped-for and desired results.
Accordingly, basic identifying characteristics pertinent to the claimed genera are left unanswered, including threshold questions, such as “which structures do or do not satisfy the functional limitations at instant claims 1, 7, 10 and 11?”.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems, biochemistry, neighboring effects of amino acids in polypeptides, etc. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what compounds would be capable of satisfying the functional “wherein” limitations recited at claims 1, 7, and 10-11.
This lack of predictability is pertinent because close prior art exists on record (i.e., US 9458211 at SEQ ID NO: 60 as applied below, wherein that discussion is incorporated into the instant rejection; see also US20150299265A1 at SEQ ID NO: 114, which was applied in the Requirement, wherein that discussion is incorporated herein). These examples are not exhaustive, and Applicant is directed to the search notes, which identify numerous prior art sequences that appear to satisfy the positively recited structural limitations set forth in the body of claims 1 and 7. However, assuming that the “wherein” clauses are functional limitations, it is prima facie unclear if such prior art sequences satisfy the “wherein” clauses or not in the complete absence of a corresponding structure/function relationship on record. This is relevant because the courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, if the functional limitations at claims 1, 7, and 10-11 do not permit an artisan to distinguish amount infringing and non-infringing embodiments, “the inventor cannot lay claim to the subject matter”.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “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” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures infringe or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claims 1-11 and 16 are rejected.
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 1-7, 10-11, and 16 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 9458211 (Oct. 4, 2016).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1-7, 10-11, 16, and the “wherein” clauses at claims 1, 7, and 10-11, the “wherein” clauses (e.g., “wherein said ankyrin repeat domain has binding specificity for CD40” at claims 1 and 7) at claims 1, 7, and 10-13 do not correspond to a structure/function relationship of record and therefore are not reasonably considered functional limitations. This is reasonable, because the term “CD40” fails to correspond to a single polypeptide, but instead corresponds to genus including unspecified homologs and variants, and therefore there is no single, unique “CD40” structure that a claimed polypeptide must bind (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40). Rather, such recitations are understood for purposes of the instant rejection to be recitations of intended and expected results, fully satisfied by all polypeptides satisfying the positively recited structural limitations set forth in the body of claims 1 and 7 (see, e.g., MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that . . . . does not limit a claim to a particular structure”). Accordingly, the “wherein” clauses at claims 10-13 are understood to be fully satisfied by any structure reading upon instant claim 1 or 7 for purposes of the instant rejection.
Regarding instant claims 7, 10-11, and sequences sharing “at least 80%” sequence identity with instant SEQ ID NO: 29, US’211 teaches and discloses SEQ ID NO: 60, which has the sequence of
>ARH61894.1 Sequence 60 from patent US 9458211
DLGKKLLEAARAGQDDEVRELLKAGADVNAKDYFSHTPLHLAARNGHLKIVEVLLKAGADVNAKDFAGKTPLHLAANEGHLEIVEVLLKAGADVNAQDIFGKTPADIAADAGHEDIAEVLQKAAGSPTPTPTTPTPTPTTPTPTPTGSDLGKKLLEAARAGQDDEVRILLKAGADVNAKDRYGDTPLHLAADIGHLEIVEVLLKAGADVNAEDYFGNTPLHLAASYGHLEIVEVLLKAGADVNAKDDYGNTPLHLAANTGHLEIVEVLLKAGADVNAQDKSGKTPADLAADAGHEDIAEVLQKAA
The highlighted portion shares 85% sequence identity with instant SEQ ID NO: 29 (i.e., 135/159 identities) (compare US’211 at SEQ ID NO: 60 with instant SEQ ID NO: 29, showing 135/159 identities):
PNG
media_image1.png
263
747
media_image1.png
Greyscale
Regarding instant claims 1-4 and a sequence comprising an ankyrin repeat module selected from sequences in which up to 10 amino acids in instant SEQ ID NOs: 76-7813 are substituted by other amino acids, US’211 teaches and discloses SEQ ID NO: 60, which comprises a first subsequence of KDRYGDTPLHLAADIGHLEIVEVLLKAGADVNA, which shares 82% sequence identity with instant SEQ ID NO: 76 (i.e., 27/33 identities)
PNG
media_image2.png
117
531
media_image2.png
Greyscale
SEQ ID NO: 60 of US’211 comprises a second subsequence having the sequence EDYFGNTPLHLAASYGHLEIVEVLLKAGADVNA, which shares 78% sequence identity with instant SEQ ID NO: 77 (i.e., 26/33 identities):
PNG
media_image3.png
111
525
media_image3.png
Greyscale
SEQ ID NO: 60 of US’211 comprises a third subsequence having the sequence KDDYGNTPLHLAANTGHLEIVEVLLKAGADVNA, which shares 82% sequence identity with instant SEQ ID NO: 78 (i.e., 27/33 identities):
PNG
media_image4.png
110
528
media_image4.png
Greyscale
The first subsequence is located at the N-terminal of the second subsequence, and the second subsequence is located at the N-terminal of the third subsequence (compare US’211 at SEQ ID NO: 60 with instant SEQ ID NO: 29 and claims 1-4).
Regarding instant claim 5 and an N-terminal capping module, US’211 teaches and discloses SEQ ID NO: 60, which comprises an N-capping module of GSDLGKKLLEAARAGQDDEVRILLKAGADVNA, which shares 94% sequence identity (i.e., 30/32 identities) with instant SEQ ID NO: 514 as shown below:
PNG
media_image5.png
114
525
media_image5.png
Greyscale
(compare US’211 at SEQ ID NO: 60 with instant SEQ ID NOs: 5, 29, and claim 5).
Regarding instant claim 6 and the presence of a C-terminal capping module, US’211 teaches and discloses SEQ ID NO: 60, which comprises a C-terminal capping module, namely QDKSGKTPADLAADAGHEDIAEVLQKAA, which shares 93% sequence identity (26/28 identities) with instant SEQ ID NO: 1315, as shown below:
PNG
media_image6.png
118
408
media_image6.png
Greyscale
(compare US’211 at SEQ ID NO: 60 with instant SEQ ID NOs: 13, 29, and claim 6).
Regarding instant claim 16 and a “pharmaceutical composition” comprising the protein of claim 7 and “optionally a pharmaceutically acceptable carrier and/or diluent”, in view of the disclosure of US’211 at SEQ ID NO: 60, an artisan would at once envisage a purified polypeptide consisting of SEQ ID NO: 60 in an aqueous solution, as would be required to make and use SEQ ID NO: 60 in any biological assays and applications. Furthermore, per MPEP § 2111.04(I), claim scope is not limited by claim language that makes optional but doe not require a particular structure or step.
Accordingly, claims 1-7, 10-11, and 16 are rejected as anticipated in view of the prior art.
Examiner Notes
Per MPEP 2001 and 37 CFR 1.56, there is a duty to disclose information material to patentability. Applicant is advised that any prior art document known to the Applicants pertaining to, claiming, or otherwise disclosing any compound sharing 80% sequence identity to one or more of the instantly claimed polypeptides, is relevant to prosecution, and should be identified in an IDS in any subsequent response (e.g., prior patents or patent applications in any country, poster sessions, dissertations, press releases, slide presentations given at public events, etc., etc.).
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Li et al16 pertains to ankyrin repeats and using the motif to mediate protein-protein interactions (see, e.g., Li at title, abs, passim).
US20150299265A1 (Oct. 4, 2016) teaches and discloses SEQ ID NO: 114, and sequences that appear to be related to those instantly claimed.
US 9284361 discloses SEQ ID NO: 51 and other sequences that appear related to those instantly claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 See, e.g., Reply filed 8/25/2025 at 2, noting that 80% sequence identity with any one of SEQ ID NOs: 16-35 is alleged to be the shared feature of all claims.
2 See, e.g., Reply filed 8/25/2025 at 2, noting that 80% sequence identity with any one of SEQ ID NOs: 16-35 is alleged to be the shared feature of all claims.
3 I.e., the “wherein” clause of “wherein said ankyrin repeat domain has binding specificity for CD40” at claim 1 is understood to be fully satisfied by any protein “comprising an amino acid sequence selected from the group consisting of” SEQ ID NOs: 39-95 or “sequences in which up to 10 amino acids in any of SEQ ID NOs: 39 to 95 are substituted by other amino acids”.
4 I.e., the “wherein” clause of “wherein said ankyrin repeat domain has binding specificity for CD40” at claim 1 is understood to not be fully satisfied by all proteins “comprising an amino acid sequence selected from the group consisting of” SEQ ID NOs: 39-95 or “sequences in which up to 10 amino acids in any of SEQ ID NOs: 39 to 95 are substituted by other amino acids”, but rather a narrower subgenus of sequences that additionally satisfy a structure/function relationship corresponding to the functional limitation.
5 Furthermore, CD40 is defined to be a potentially highly varied genus of numerous polypeptides, rather than a single structure (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40), and no structure/function relationship regarding the range of unknown CD40 “variants” has been disclosed on record.
6 I.e., wherein claim 7 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited structural limitations set forth in the body of the claim, namely any amino acid comprising a sequence sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
7 I.e., the “wherein” clause of “wherein said ankyrin repeat domain has binding specificity for CD40” at claim 1 is understood to not be fully satisfied by all proteins sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”, but rather a narrower subgenus of sequences that additionally satisfy a structure/function relationship corresponding to the functional limitation.
8 Furthermore, CD40 is defined to be a potentially highly varied genus of numerous polypeptides, rather than a single structure (see, e.g., Spec. filed 8/07/2023 at 34 at lines 32-40), and no structure/function relationship regarding the range of unknown CD40 “variants” has been disclosed on record.
9 I.e., wherein claim 7 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited structural limitations set forth in the body of the claim, namely any amino acid comprising a sequence sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
10 I.e., the “wherein” clause of “wherein said ankyrin repeat domain has binding specificity for CD40” at claim 1 is understood to not be fully satisfied by all proteins sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”, but rather a narrower subgenus of sequences that additionally satisfy a structure/function relationship corresponding to the functional limitation.
11 I.e., wherein claim 7 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited structural limitations set forth in the body of the claim, namely any amino acid comprising a sequence sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”.
12 I.e., the “wherein” clause of “wherein said ankyrin repeat domain has binding specificity for CD40” at claim 1 is understood to not be fully satisfied by all proteins sharing “at least 80% amino acid sequence identity with any one of SEQ ID NOs: 16-35, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 16 to 35 are optionally missing”, but rather a narrower subgenus of sequences that additionally satisfy a structure/function relationship corresponding to the functional limitation.
13 Instant SEQ ID NO: 76 (KDTWGFTPLHIAAESGHLEIVEVLLKAGADVNA);
Instant SEQ ID NO: 77 (KDVQGRTPLHIAAHSGHLEIVEVLLKAGADVNA); and
Instant SEQ ID NO: 78 (KDFRGWTPLHLAAWSGHLEIVEILLKAGADVNA).
14 Instant SEQ ID NO: 5 is GSDLGKKLLQAARAGQLDEVRELLKAGADVNA
15 Instant SEQ ID NO: 12 is QDKFGKTPADIAADNGHEDIAEVLQKLN;
Instant SEQ ID NO: 13 is QDKSGKTPADLAARAGHQDIAEVLQKAA;
Instant SEQ ID NO: 14 is QDTQGTTPADLAARAGHQQIASVLQQAA; and
Instant SEQ ID NO: 15 is XDXXGXTPADXAARXGHQXIAXVLQXAA.
16 Li et al, Ankyrin repeat: a unique motif mediating protein-protein interactions. Biochemistry. 2006 Dec 26;45(51):15168-78. doi: 10.1021/bi062188q. PMID: 17176038; hereafter “Li”.
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