DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/28/2025 has been entered.
Claim Status
Claims 215-218, 222, 226-228, and 252-289 are pending. Claims 223-225 and 229-251 were canceled; claims 218 and 222 were amended; and claims 252-289 were newly added in the Reply filed 10/28/2025. Claims 226-228, 274-276, and 287-289 are withdrawn. Claims 215-218, 222, 252-273, and 277-286 are pending. No claims are allowed.
Election/Restriction
Applicant’s election without traverse of the species of polypeptide of SEQ ID NO: 1 in the reply filed on 9/27/2024 was previously acknowledged.
The originally elected species of SEQ ID NO: 11, and SEQ ID NOs: 22, 33, 44, 5545, 3656, 3637, and 3588 were previously deemed free of the prior art. However, following the Final Rejection mailed 4/28/2025, US2025/0195673 A1 was published, corresponding to copending Application No. 18/037,923, which was not previously identified in an IDS. This has necessitated a non-statutory double patenting rejection over the originally elected species and SEQ ID NOs: 2-3 and 554, among others, as set forth below. All prior determinations of allowable subject matter are hereby withdrawn as premature. This action is non-final.
Claims 226-228, 274-276, and 287-289 do not read upon the originally elected species, and are presently withdrawn.
Claims 226-228, 274-276, and 287-289 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/27/2024.
Claims 215-218, 222, 252-273, and 277-286, are pending and presently considered.
Priority
The priority claim to US Provisional Application 63/273,103 (filed 10/28/2021) is acknowledged.
Information Disclosure Statement
The IDS submitted 10/28/2025 is acknowledged and presently considered.
Specification
The disclosure is objected to because of the following informalities:
The specification incorrectly identifies that Figure 21 shows “red” (see, e.g., Spec. at ¶[0418]) and that Figure 6A shows “cyan” (see, e.g., Spec. at ¶[0414]). The drawings are in grayscale and do not show colors.
Appropriate correction is required.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show colors as described in the specification (see, e.g., Spec. at ¶[0418], stating that Figure 21 shows “red”; see, e.g., Spec. at ¶[0414], stating that Figure 6A shows “cyan”). Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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.
Amended claims 215, 252, 261, and 277 are representative of the pending claim scope. Applicable claim interpretations are discussed below.
Regarding the preamble phrase “A PD-L1-binding peptide”, 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 the independent claims are understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the structures recited in the body of the claim (see also MPEP § 2111.04(I)).
“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)).
At claims 253-260, the references to “at least 80%[or 90%] sequence identity” are understood to satisfy 35 USC § 112(d) because the dependent claims are understood to simultaneously include the limitations of claim 215 and each of claims 253-260. This means, for example, that claim 253 requires the sequence of claim 215 (i.e., SEQ ID NO: 365) to remain unchanged, and that only non-underlined portions of SEQ ID NO: 1 as shown below can be varied at dependent claim 253:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
If limitations were not resolved simultaneously, claims 253-260 would be properly rejected under 35 USC §112(d) as it would imply the dependent claims more broadly encompassed sequences wherein SEQ ID NO: 365, which is a part of SEQ ID NO: 1-3 and 554, could be varied. This “simultaneous” interpretation of independent and dependent claim limitations is consistent with the Examiner’s prior interpretation of record for previously pending claim 224 (see, e.g., Action mailed 4/28/2025 at 6 at 2nd ¶).
Sequence identity of an “X” residue: Variable “X” positions do not count as identities in sequence alignments. For example, Examiner notes that attempts to align the variable sequence of SEQ ID NO: 363 and instant SEQ ID NO: 1 using basic alignment tools (e.g., BLAST) yields:
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This illustrates a nuance of sequence alignments, namely “sequence identity” requires an “identity” or an exact, unique match. Accordingly, an “X” residue shares 0% sequence identity with any specific amino acid residue.
Newly added claims 262-269 refer to sequences sharing “at least 80%[or 90%] sequence identity” to one of SEQ ID NOs: 1-3 and 554, but simultaneously require such sequences to comprise the variable motif of X1FX2VFX2CLX3X3C (SEQ ID NO: 363), which is understood to align and correspond to a first PD-L1-binding motif within each of SEQ ID NOs: 1-3 and 554, as exemplified by SEQ ID NO: 1 below:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQX1FX2VFX2CLX3X3CAAP
This raises a material and substantial concern regarding whether or not the variable “X” residues within SEQ ID NO: 1 (or SEQ ID NOs: 2-3 and 554) contribute to the determination of percent sequence identity in dependent claims 262-269, or not. As explained above, an “X” residue shares 0% sequence identity with any unique amino acid. Accordingly, if the sequence identity limitations of claims 262-269 are applied simultaneously, then the maximum common residues contributing to sequence identity begins at 44/49 residues9 (i.e., 89.79% maximum sequence identity). Accordingly, applying the limitations of the independent and dependent claims simultaneously precludes claims 263, 265, 267, and 269 from including any species because the recited limitations preclude a determination of sequence identity over 89.79% (i.e., claims to 90% sequence identity do not read upon any embodiments). This “simultaneous” interpretation of independent and dependent claim limitations is consistent with the Examiner’s prior interpretation of record for previously pending claim 224 (see, e.g., Action mailed 4/28/2025 at 6 at 2nd ¶; see also discussion above with respect to claims 253-260); however, instant claims 262-269 raise substantial and material concerns regarding the proper interpretation of such claims because a “simultaneous” interpretation of limitations renders claims 263, 265, 267, and 269 automatically rejected as no embodiments would have a sequence identity over 90% as required by the claims. Accordingly, this issue has necessitated rejections under 35 USC §112, below.
New claim 277 requires a peptide comprising a sequence of SEQ ID NO: 358:
[EMVW][GELF][DES]C[KRV][EQSMLV][DEHKRNQSY]C[DMV][AKRQST][ADEHQSTMILVW][AERQSTWP][AEKRNQTMILVW][GAEKNTY][GADEHKRNQSTMILVWYP][DKRNLV][GADTLWP]C[GAEHKNSFP][GADENP][GDHKRNQSTVY][GDEHKNQSTMIFWYP][GADEHKRNQSYP][GADHNQSVFP][ADHNQSTMIVYP][GADKRTWY][GAENQTIVP][GDNQTLVFP][GAEKRNQSTIYP][ADNI][GDEHNFW]C[GAENSYP][GML][GADKNQW][DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKRMLP]C[GAKSIL][GADERQTF][AHNQSFP]
wherein amino acids within brackets identify alternative possibilities at a single position of the motif, and the highlighted portion corresponds to the same second binding motif of SEQ ID NO: 360, and the highlighted and underlined portion corresponds to SEQ ID NO: 361.
Newly added claims 278-285 refer to sequences sharing “at least 80%[or 90%] sequence identity” to one of SEQ ID NOs: 1-3 and 554, but simultaneously require such sequences to comprise the variable 49-mer motif of SEQ ID NO: 358, which is understood to align and correspond to a first PD-L1-binding motif within each of SEQ ID NOs: 1-3 and 554. For example, SEQ ID NO: 1 is
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
But upon simultaneously combining the limitations of SEQ ID NO: 277 with any of claims 278-285, the dependent claims 278-285 require sequences sharing “at least 80%[or 90%] sequence identity” to a sequence of
XXXCXXXCXXXXXXXXXCXXXXXXXXXXXXXCXXXXXXXXXCXXXCXXX
As explained above, an “X” residue shares 0% sequence identity with any unique amino acid. Critically, this means that any possible sequence could only share, at most, 6/49 residues in common with any of SEQ ID NOs: 1-3 or 554 (i.e., a maximum of 12.24% sequence identity using BLAST or other alignment tools for sequence identity). Accordingly, applying the limitations of the independent and dependent claims simultaneously precludes claims 278-285 from including any species because the recited limitations preclude a determination of sequence identity over 12.24% (i.e., claims to 80% or 90% sequence identity cannot read upon any embodiments). This “simultaneous” interpretation of independent and dependent claim limitations is consistent with the Examiner’s prior interpretation of record for previously pending claim 224 (see, e.g., Action mailed 4/28/2025 at 6 at 2nd ¶); however, instant claims 278-285 raise substantial and material concerns regarding the proper interpretation of such claims because a “simultaneous” interpretation renders claims 278-285 automatically rejected as no embodiments would have a sequence identity over 12.24%, and therefore zero embodiments would satisfy the requirements of the claim. Accordingly, this issue has necessitated rejections under 35 USC §112, below.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejections of claims 217-218, 223, 225, 240, and 245 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, are withdrawn-in-part in view of the amendments filed 10/28/2025 canceling claims 223, 225, 240, and 245, and amending claim 218. Remaining or new issues are set forth below in a revised rejection as necessitated by Applicant’s amendments.
The rejection of claims 223 and 225 under 35 U.S.C. 102(a)(1) as being clearly anticipated by Vaz et al.10 is withdrawn as moot in view of the cancellation of claims 223 and 225.
The rejection of claims 223 and 225 under 35 U.S.C. 102(a)(1) as being clearly anticipated by El-kereamy et al.11 is withdrawn as moot in view of the cancellation of claims 223 and 225.
Denial of 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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Provisional US Application 63/119,195 (filed 11/30/2020), fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163.
Lack of Express Support
Claims 215-218, 222, 226-228, and 252-289 are pending and are representative of the pending claim scope. These claims do not literally appear in the provisional document, and therefore the claims lack literal support in the Pro’195.
Accordingly, Pro’195 fails to provide literal support for the pending claim scope that is synonymous or equivalent in scope.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163. In the absence of express support, the relevant issue is whether or not the claimed invention is supported by Pro’231 through implicit or inherent disclosures.
Upon review, zero inherent or implicit support commensurate in scope with the metes and bounds of the instant claims is found in Pro’195, at least because instant claims 215-218, 222, 226-228, and 252-289 do not literally, implicitly, or inherently appear, as instantly claimed, in the provisional document.. According the claim language presently claimed is not supported by the provisional document by synonymous or equivalent language.
Accordingly, Pro’195 fails to provide implicit or inherent support for the pending claim scope that synonymous or equivalent in scope, or otherwise commensurate in scope with the pending claims.
Conclusion
Accordingly, priority to Provisional US Application 63/119,195 (filed 11/30/2020) is denied for all claims; these claims have been accorded a priority date of 10/28/2020, which corresponds to the filing date of US Provisional Application 63/273,103 (filed 10/28/2021)
New or Revised Claim Rejections as Necessitated by Applicant’s Amendments
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 217-218, 262-269, 271-272, 278-285, and 286, 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 217 is rejected as indefinite because it requires “at least six cysteines”, which are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, “wherein n corresponds to a position of a first cysteine residue” (see claim 217), but the “first cysteine” lacks antecedent basis. It is unclear if the “first cysteine” refers to a cysteine in SEQ ID NO: 365 as recited at claim 215, or if the “first cysteine” is located within an N-terminal extension or C-terminal extension relative to SEQ ID NO: 365, because SEQ ID NO: 365 does not contain “at least six cysteines” and no cysteine has actually been designated or unambiguously identified as the “first cysteine”. Accordingly, there is insufficient antecedent basis for this limitation (“first cysteine residue”) in the claim.
Claim 217 is rejected as indefinite because it recites “first cysteine”, which is undefined on record and appears to be a relative term depending upon an unknown overall structure and unknown usage of “first”. The term “first” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree but instead provides different interpretations and guidance (see below), and therefore one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if “first” means
(i) the most N-terminal cystine residue, which may be in an N-terminal extension relative to SEQ ID NO: 365 in claim 215, from which claim 217 depends (see, e.g., Spec. filed 5/19/2023 at ¶[0192]);
(ii) the “first” cysteine of SEQ ID NO: 365 as required by claim 215;
(iii) the cysteine that forms a disulfide bond between itself and another cysteine located +42 amino acids towards the C-terminal (see, e.g., Spec. filed 5/19/2023 at ¶[0019]); or
(iv) the cysteine corresponding to “n” within a “first alpha helix comprising residues n to n+20” and a “second alpha helix comprising residues n +34 to n+44” (see, e.g., Spec. filed 5/19/2023 at ¶[0020]);
(v) “the N-terminal amino acid residue of the second PD-L1-binding motif [that is] located at amino acid residue position n” (see, e.g., Spec. filed 5/19/2023 at ¶[0022]);
(vi) The fourth amino acid from the N-terminus of the full-length claimed peptide (see, e.g., Spec. filed 5/19/2023 at ¶[0037]);
(vii) The cysteine that forms a disulfide bond with the “fourth residue” (presumably n+28) (see, e.g., Spec. filed 5/19/2023 at ¶[0183]); or
(viii) something else.
Accordingly, it is unclear what is meant or implied by “first” in view of the claims and instant specification in the instant context. Therefore, claim 217 is rejected as indefinite.
Claim 217 is rejected as indefinite because it requires “at least six cysteines”, which are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, which raises concerns regarding the existence and placement of additional cysteine residues. Specifically, it is unclear if Claim 217 requires six cysteines having the following relative arrangement:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Wherein any additional cysteines must be located in an N- or C-terminal extension of such a motif, or if additional cysteines may be located at any position within such arrangement:
CnXCCXCn+4XXCXXXCXXCn+14XXXXXCCCXXXXXCn+28XXXXCCXXXCn+38XXXCn+42
Or simply poly(Cys)42. Accordingly, it is unclear if the “n +” notation excludes placement of additional Cysteine residues between the cysteines identified as n, n+4, n+14, n+28, n+38, and n+42; or if additional cysteine residues may be placed between the cysteines identified as n, n+4, n+14, n+28, n+38, and n+42. This difference substantially alters the pending claim scope. Accordingly, it is unclear what embodiments would infringe upon the claim or not, and the courts have stated that “[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, the claim is rejected as indefinite.
Claim 217 is rejected as indefinite because it depends upon a reference to an object that is variable (see, e.g., MPEP § 2173.05(b)(II)). Claim 217 requires a peptide that comprises SEQ ID NO: 365 (i.e., KFDVFKCLDHC) and “at least six cysteines”, wherein the “at least six cysteines” are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, “wherein n corresponds to a position of a first cysteine residue”. As noted above, the term “first cysteine residue” lacks antecedent basis. In addition, assuming the N-terminal most cysteine is deemed the “first cysteine”, the claim scope remains indefinite because the relative designation of the two cysteines within SEQ ID NO: 365 are variable, unknown, and unspecified. For example, the cysteines in SEQ ID NO: 365 may be “n” and “n+4”:
KFDVFKCnLDHCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Or the cysteines in SEQ ID NO: 365 may be “n+38” and “n+42”:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXKFDVFKCn+38LDHCn+42
Or the only one of the cysteines in SEQ ID NO: 365 may be deemed to be within the enumerated positions of claim 217:
CnXXXXCn+4XXXKFDVFKCn+14LDHCXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Or
CnXXXXCn+4XXXXXXXXXCn+14XXXKFDVFKCLDHCn+28XXXXXXXXXCn+38XXXCn+42
Or the cysteines in SEQ ID NO: 365 may not correspond to any of “n”, “n+4”, “n+14”, n+28”, “n+38” or “n+42”:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42KFDVFKCLDHC
Or
CnXXXXCn+4XXXXXXXXXCn+14XKFDVFKCLDHCXCn+28XXXXXXXXXCn+38XXXCn+42
These examples are not exhaustive and presume that “first” in “first cysteine” refers to the N-terminal most cysteine. Accordingly, the limitations of claim 217 fail to unambiguously inform artisans of what the structural relationship is between the cysteines already present in SEQ ID NO: 365, and the placement requirements for all additional cysteines and cysteine locations as recited at claim 217. As exemplified above, this directly impacts the pending claim scope and impacts what structures are included or excluded from the pending claim scope. Accordingly, the reference to objects that are variable renders the pending claim scope indefinite because the metes and bounds of the claim scope vary depending upon the arbitrary labeling of unspecified cysteines (see, e.g., MPEP § 2173.05(b)(II), noting that when the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite).
Claim 218 depends from amended claim 217, and presently recites “amino acid position n corresponds to amino acid position 4”. There is insufficient antecedent basis for “amino acid position 4” in the claim. Reference to “amino acid position 4” raises the question “position 4 of what sequence?”, which is not answered at claim 218 or the claims upon which it depends. Specifically, it is unclear (i) if “amino acid position 4” refers to SEQ ID NO: 365 (which would raise concerns under 35 USC §112(d)); (ii) if “amino acid position 4” refers to a subsequence of SEQ ID NO: 365; (iii) if “amino acid position 4” refers to a wholly unknown and unspecified sequence; or (iv) if the “position 4” designation is simply an arbitrary designation since claim 215 recites “comprising” (i.e., open-ended) rather than “consisting of” language, and therefore any position arbitrarily deemed “1” or “4” may be arbitrarily shifted C-terminally by the addition of an additional N-terminal extension moieties, which would presumably be arbitrarily identified as positions “n-1” to “n-x”, where x is the actual N-terminus. Accordingly, the reference to “amino acid position 4” lacks antecedent basis and renders the claim scope indefinite.
Newly added claims 262-269 refer to sequences sharing “at least 80%[or 90%] sequence identity” to one of SEQ ID NOs: 1-3 and 554, but simultaneously require such sequences to comprise the variable motif of X1FX2VFX2CLX3X3C (SEQ ID NO: 363), which renders the claim scope indefinite. Variable “X” positions do not count as identities in sequence alignments: Examiner notes that attempts to align variable sequences containing “X” residues using basic alignment tools (e.g., BLAST) yields:
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This result illustrates a nuance of sequence alignments, namely that variable “X” residues are not “identities” because an “identity” requires a single, unique match. Due to this nuance of variable positions and sequence alignments, the correct handling of limitations involving variable residues and sequence identity requirements give rise to indefiniteness issues because claim scope varies depending upon how such limitations interact, which is not clear in view of the art and instant disclosure. One way that the claim scope may reasonably be evaluated is by simultaneously applying the limitations of both the independent and dependent claims: Claims 261-269 requires a PD-L1-binding protein that comprises SEQ ID NO: 363 (X1FX2VFX2CLX3X3C) as well as one sequence sharing at least 80% (or 90%) sequence identity with one of SEQ ID NOs: 1-3 and 554. However, SEQ ID NOs: 1-3 and 554 actually fully comprise SEQ ID NO: 363; for example, SEQ ID NO: 1 actually comprises SEQ ID NO: 363 at the highlighted portion:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
Therefore, the claim scope reads upon SEQ ID NOs: 1-3 and 554 modified to simultaneously account for the variability of SEQ ID NO: 363, which yields a modified sequence, such as the modified SEQ ID NO: 1 shown below:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQX1FX2VFX2CLX3X3CAAP
Notably, applying the limitations requiring “90% sequence identity” to such embodiments, automatically fails because such sequences can at most only share 44/49 identities, or 89.79%12 sequence identity even with itself (alignment below shows SEQ ID NO: 1 aligned with the modified SEQ ID NO: 1 above):
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Accordingly, such an interpretation results in a conclusion that claims 263, 265, 267, and 269 read upon zero embodiments; and for claims 262, 264, 266, and 268, it implies that such claims could only have up to four additional mutations at non-overlapping positions relative to SEQ ID NOs: 1, which may only be located in a highlighted area:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQXFXVFXCLXXCAAP
Therefore, as a hypothetical example, this interpretation would imply that a sequence such as
EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP13
would be excluded from the pending claim scope because it only shares 39/49 residues14 (less than 80% sequence identity) in common with instant SEQ ID NO: 1.
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Accordingly, given a “simultaneous” interpretation of the X positions and sequence identity limitations, claims 263, 265, 267, and 269 read upon zero embodiments; and claims
such embodiments would be excluded from claims 262, 264, 266, and 268, it implies that such claims could only have up to four additional mutations, and would exclude embodiments as shown above. A second possible claim interpretation is to resolve the limitation of the independent claim and then apply the limitations of the dependent claims directly: The independent claim recites X1FX2VFX2CLX3X3C (SEQ ID NO: 363), which is a variable genus of sequences, which, when resolved contains 2,888 different species15, which may not be varied at positions 2, 4-5, 7-8, or 11. However, the dependent claims recite and refer to sequences comprising SEQ ID NO: 363, but are not limited to sequences that do not vary at positions 2, 4-5, 7-8, or 11 od SEQ ID NO: 363, and are not limited to the subgenera corresponding to X1, X2, or X3 at the independent claim (i.e., X1 may be C, H, R, L, E, Q, etc.). Under this interpretation, claims 262-269 would be rejected under 35 USC § 112(d) for failing to include the limitations of the claim upon which they depend. As a third possible interpretation, the variable limitations of the independent claim could be resolved and then the limitations of the dependent claim could be separately applied only to embodiments satisfying the independent claim: The independent claim recites X1FX2VFX2CLX3X3C (SEQ ID NO: 363), which is a variable genus of sequences, which, when resolved contains 2,888 different species16, which may not be varied at positions 2, 4-5, 7-8, or 11. Using the hypothetical sequence discussed above, namely:
EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP17
The portion corresponding to SEQ ID NO: 363 would be resolved first, for example to
EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQPFKVFDCLDHCAAP18
This example sequence would align to instant SEQ ID NO: 1 as follows:
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Accordingly, this example, which was excluded in the first interpretation, would be understood to satisfy the limitations of instant claim 262 but not claim 263. In sum, claims 262-269 are rejected as indefinite because they conflate limitations having variable “X” residues and limitations having minimum sequence identity requirements, which may reasonably be interpreted in different manners, and zero guidance on record is provided for how to handle variable “X” residues when applying sequence identity requirements. As noted above, depending upon how the limitations are applied, the claim scope may be altered, as well as the applicable claim rejections. Clarification is required. Examination in view of the prior art is currently precluded. In the absence of clear guidance regarding the interpretation and interaction of sequence identity requirements and variable positions, it is unclear what embodiments would infringe upon the claim or not, and the courts have stated that “[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, the claim is rejected as indefinite (see, e.g., MPEP § 2173.05(b)(II), noting that when the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite).
Claim 271 is rejected as indefinite because it requires “at least six cysteines”, which are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, “wherein n corresponds to a position of a first cysteine residue” (see claim 271), but the “first cysteine” lacks antecedent basis. It is unclear if the “first cysteine” refers to a cysteine in SEQ ID NO: 363 as recited at claim 261, or if the “first cysteine” is located within an N-terminal extension or C-terminal extension relative to SEQ ID NO: 363, because SEQ ID NO: 363 does not contain “at least six cysteines” and no cysteine has actually been designated or unambiguously identified as the “first cysteine”. Accordingly, there is insufficient antecedent basis for this limitation (“first cysteine residue”) in the claim.
Claim 271 is rejected as indefinite because it recites “first cysteine”, which is undefined on record and appears to be a relative term depending upon an unknown overall structure and unknown usage of “first”. The term “first” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree but instead provides different interpretations and guidance (see below), and therefore one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if “first” means
(i) the most N-terminal cystine residue, which may be in an N-terminal extension relative to SEQ ID NO: 365 in claim 215, from which claim 217 depends (see, e.g., Spec. filed 5/19/2023 at ¶[0192]);
(ii) the “first” cysteine of SEQ ID NO: 363 as recited at claim 261;
(iii) the cysteine that forms a disulfide bond between itself and another cysteine located +42 amino acids towards the C-terminal (see, e.g., Spec. filed 5/19/2023 at ¶[0019]); or
(iv) the cysteine corresponding to “n” within a “first alpha helix comprising residues n to n+20” and a “second alpha helix comprising residues n +34 to n+44” (see, e.g., Spec. filed 5/19/2023 at ¶[0020]);
(v) “the N-terminal amino acid residue of the second PD-L1-binding motif [that is] located at amino acid residue position n” (see, e.g., Spec. filed 5/19/2023 at ¶[0022]);
(vi) The fourth amino acid from the N-terminus of the full-length claimed peptide (see, e.g., Spec. filed 5/19/2023 at ¶[0037]);
(vii) The cysteine that forms a disulfide bond with the “fourth residue” (presumably n+28) (see, e.g., Spec. filed 5/19/2023 at ¶[0183]); or
(viii) something else.
Accordingly, it is unclear what is meant or implied by “first” in view of the claims and instant specification in the instant context. Therefore, claim 271 is rejected as indefinite.
Claim 271 is rejected as indefinite because it requires “at least six cysteines”, which are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, which raises concerns regarding the existence and placement of additional cysteine residues. Specifically, it is unclear if Claim 271 requires six cysteines having the following relative arrangement:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Wherein any additional cysteines must be located in an N- or C-terminal extension of such a motif, or if additional cysteines may be located at any position within such arrangement:
CnXCCXCn+4XXCXXXCXXCn+14XXXXXCCCXXXXXCn+28XXXXCCXXXCn+38XXXCn+42
Or simply poly(Cys)42. Accordingly, it is unclear if the “n +” notation excludes placement of additional Cysteine residues between the cysteines identified as n, n+4, n+14, n+28, n+38, and n+42; or if additional cysteine residues placed between the cysteines identified as n, n+4, n+14, n+28, n+38, and n+42 is not excluded. This difference substantially alters the pending claim scope. Accordingly, it is unclear what embodiments would infringe upon the claim or not, and the courts have stated that “[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, the claim is rejected as indefinite.
Claim 271 is rejected as indefinite because it depends upon a reference to an object that is variable (see, e.g., MPEP § 2173.05(b)(II)). Claim 271 requires a peptide that comprises SEQ ID NO: 363 and “at least six cysteines”, wherein the “at least six cysteines” are located at “amino acid positions n, n+4, n+14, n+28, n+38, and n+42”, “wherein n corresponds to a position of a first cysteine residue”. As noted above, the term “first cysteine residue” lacks antecedent basis. In addition, assuming the N-terminal most cysteine is deemed the “first cysteine”, the claim scope remains indefinite because the relative designation of the two cysteines within SEQ ID NO: 363 are variable, unknown, and unspecified. For example, the cysteines in SEQ ID NO: 363 may be “n” and “n+4”:
KFDVFKCnLDHCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Or the cysteines in SEQ ID NO: 363 may be “n+38” and “n+42”:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXKFDVFKCn+38LDHCn+42
Or the only one of the cysteines in SEQ ID NO: 363 may be deemed to be within the enumerated positions of claim 271:
CnXXXXCn+4XXXKFDVFKCn+14LDHCXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42
Or
CnXXXXCn+4XXXXXXXXXCn+14XXXKFDVFKCLDHCn+28XXXXXXXXXCn+38XXXCn+42
Or the cysteines in SEQ ID NO: 363 may not correspond to any of “n”, “n+4”, “n+14”, n+28”, “n+38” or “n+42”:
CnXXXXCn+4XXXXXXXXXCn+14XXXXXXXXXXXXXCn+28XXXXXXXXXCn+38XXXCn+42KFDVFKCLDHC
Or
CnXXXXCn+4XXXXXXXXXCn+14XKFDVFKCLDHCXCn+28XXXXXXXXXCn+38XXXCn+42
These examples are not exhaustive and presume that “first” in “first cysteine” refers to the N-terminal most cysteine. Accordingly, the limitations of claim 271 fail to unambiguously inform artisans of what the structural relationship is between the cysteines already present in SEQ ID NO: 363, and the placement requirements for all additional cysteines and cysteine locations as recited at claim 271. As exemplified above, this directly impacts the pending claim scope and impacts what structures are included or excluded from the pending claim scope. Accordingly, the reference to objects that are variable renders the pending claim scope indefinite because the metes and bounds of the claim scope vary depending upon the arbitrary labeling of unspecified cysteines (see, e.g., MPEP § 2173.05(b)(II), noting that when the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite).
Claim 272 depends from newly added claim 271, and presently recites “amino acid position n corresponds to amino acid position 4”. There is insufficient antecedent basis for “amino acid position 4” in the claim. Reference to “amino acid position 4” raises the question “position 4 of what sequence?”, which is not answered at claim 272 or the claims upon which it depends. Specifically, it is unclear (i) if “amino acid position 4” refers to SEQ ID NO: 363 (which would raise concerns under 35 USC §112(d)); (ii) if “amino acid position 4” refers to a subsequence of SEQ ID NO: 363; (iii) if “amino acid position 4” refers to a wholly unknown and unspecified sequence; or (iv) if the “position 4” designation is simply an arbitrary designation since claim 261 recites “comprising” (i.e., open-ended) rather than “consisting of” language, and therefore any position arbitrarily deemed “1” or “4” may be arbitrarily shifted C-terminally by the addition of an additional N-terminal extension moieties, which would presumably be arbitrarily identified as positions “n-1” to “n-x”, where x is the actual N-terminus. Accordingly, the reference to “amino acid position 4” lacks antecedent basis and renders the claim scope indefinite.
Newly added claims 278-285 are rendered indefinite because the claims refer to sequences sharing “at least 80%[or 90%] sequence identity” to one of SEQ ID NOs: 1-3 and 554, but simultaneously require such sequences to comprise the variable 49-mer motif of SEQ ID NO: 35819, which is understood to align and correspond to a first PD-L1-binding motif within each of SEQ ID NOs: 1-3 and 554. The issue of indefiniteness arises because it is unclear how “sequence identity” limitations should interact with variable “X” positions, and no clarifying guidance is provided on record or universally recognized in the prior art. Variable “X” positions do not count as identities in sequence alignments: Examiner notes that attempts to align variable sequences containing “X” residues using basic alignment tools (e.g., BLAST) yields:
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This result illustrates a nuance of sequence alignments, namely that variable “X” residues are not “identities” because an “identity” requires a single, unique match. Due to this nuance of variable positions and sequence alignments, the correct handling of limitations involving variable residues and sequence identity requirements give rise to indefiniteness issues because claim scope varies depending upon how such limitations interact, which is not clear in view of the art and instant disclosure. One way that the claim scope may reasonably be evaluated is by simultaneously applying the limitations of both the independent and dependent claims: For example, SEQ ID NO: 1 is
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
But upon simultaneously combining the limitations of claim 277 requiring SEQ ID NO: 358 with any of claims 278-285, the dependent claims 278-285 may be reasonably understood to require sequences sharing “at least 80%[or 90%] sequence identity” to a sequence corresponding to an aligned SEQ ID NO: 35820 and SEQ ID NO: 1 (or 2-3, 554), which would be:
XXXCXXXCXXXXXXXXXCXXXXXXXXXXXXXCXXXXXXXXXCXXXCXXX
Critically, given the manner in which “X” residues are interpreted as discussed above, this means that aligned sequences combining SEQ ID NO: 358 with any of SEQ ID NOs: 1-3 or 554 can, at most, share only 6/49 sequence identity with other sequences (i.e., a maximum of 12.24% sequence identity using BLAST or other alignment tools for sequence identity). Under this interpretation, claims 278-285 would not read upon any embodiments, because no embodiments could share only 6/49 identities and be able to have over 13% sequence identity as claimed. A second possible claim interpretation is to resolve the limitations of the independent claim and then apply the limitations of the dependent claim directly: Independent claim 277 recites the genus of SEQ ID NO: 358, which precludes varying six positions corresponding to Cysteines. However, the dependent claims recite and refer to all sequences comprising “at least 80%[or 90%] sequence identity” to SEQ ID NOs: 1-3 and 554, including sequences that vary at the cysteine positions of SEQ ID NO: 358. Accordingly, under this interpretation, claims 278-285 would all be rejected under 35 USC § 112(d) for failing to include the limitations of the claim upon which they depend. As a third possible interpretation, the variable limitations of the independent claim could be resolved and then the limitations of the dependent claim could be separately applied only to embodiments satisfying the independent claim: The independent claim recites SEQ ID NO: 358, which is a variable genus of sequences, which, when resolved contains >>trillions of different species:
XXXCXXXCXXXXXXXXXCXXXXXXXXXXXXXCXXXXXXXXXCXXXCXXX
If the limitations of claim 277 are resolved, it results in >>trillions of distinct species, including for example, the subgenus of:
EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQPFKVFDCLDHCAAP21
This example sequence would align to instant SEQ ID NO: 1 as follows:
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Accordingly, this subgenus of examples, which are excluded in the first interpretation, above, would be understood to satisfy the limitations of instant claim 278 but not claim 279. In sum, claims 278-285 are rejected as indefinite because they conflate limitations having variable “X” residues and limitations having minimum sequence identity requirements, which may reasonably be interpreted in different manners, and zero guidance on record is provided for how to handle variable “X” residues when applying sequence identity requirements. As noted above, depending upon how the limitations are applied, the claim scope may be altered, as well as the applicable claim rejections. Clarification is required. Examination in view of the prior art is currently precluded. In the absence of clear guidance regarding the interpretation and interaction of sequence identity requirements and variable positions, it is unclear what embodiments would infringe upon the claim or not, and the courts have stated that “[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, the claim is rejected as indefinite (see, e.g., MPEP § 2173.05(b)(II), noting that when the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite).
Claim 286 is rejected as indefinite because it refers to a “second PD-L1-binding motif” comprising a sequence of SEQ ID NO: 364; however, claim 286 depends from claim 277, which recites SEQ ID NO: 358, which is understood to already necessarily and inherently comprise a first and second “PD-L1-binding motif” (i.e., SEQ ID NO: 358 encompasses instant SEQ ID NO: 1, which comprises a first PD-L1 binding motif of SEQ ID NO: 365 (KFDVFKCLDHC) and a second PD-L1-binding motif of SEQ ID NO: 364. Accordingly, the reference to a “second PD-L1-binding motif” lacks antecedent basis as it is unclear if the limitation is intended to limit one of the existing motifs, or if it is intended to require a completely new, third PD-L1-binding motif in addition to the two existing ones. Accordingly, claims 286 is rejected as indefinite.
Accordingly, claims 217-218, 262-269, 271-272, 278-285, and 286, are rejected.
Claim Rejections - 35 USC § 112(a), New Matter
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 262-269 and 278-285 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.
Applicable Case Law
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Lack of literal Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Claims 262-269 and 278-285 do not literally appear in the originally filed disclosure. Zero, unambiguous, literal support that is synonymous or equivalent in scope is set forth on record for these claims.
Accordingly, the pending claims, having the equivalent or synonymous scope instantly claimed, do not literally or inherently appear in the originally filed disclosure.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163. As noted above, the claims are not literally or inherently supported by the originally filed disclosure. Accordingly, the relevant issue is whether or not the new amendments and resulting claim scope is implicitly or inherently supported by the originally filed disclosure.
Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”. Here, no allegation that the amendments correct an obvious error has been made. Furthermore, upon inspection, Examiner is unable to identify any single “obvious error” that would lead to the scope of the newly added claims at issue. Accordingly, the amendments cannot be said to correct an “obvious error”, but instead the amendments attempt to circumvent the issue by narrowing the claim scope to a previously unclaimed genus. As noted above MPEP § 2163.05(II) explains that the introduction of claim changes which involve narrowing the claims by introducing elements or limitations which are not supported by the as-filed disclosure is a violation of the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species). Therefore, the question is whether or not the narrowed claim scope, considered “as an integrated whole”[3], is supported by the as-filed disclosure.
The originally filed Specification and drawings fails to teach the claim scope of instant claims 262-269 or 278-285.
The closest implicit or inherent support is found in the claim set filed 5/19/2023 at dependent claims 20-23. However, these claims are improper multiple dependent claims, and therefore do not clearly define or provide, in an unambiguous manner implicit or inherent support commensurate in scope with instant claims 262-269 or 278-285 (see, e.g., MPEP § 608.01(n); 35 USC 112(e); 37 CFR 1.75(c)).
No implicit or inherent support commensurate in scope with instant claims 262-269 or 278-285 exists on record, because the scope of such claims is indefinite (see, e.g., Rejections of claims 262-269 and 278-285 under 35 USC § 112(b), as set forth above), and those discussions are incorporated into the instant rejection. In brief, these newly added claims attempt to capture sequences sharing “at least 80%[or 90%] sequence identity” to one of SEQ ID NOs: 1-3 and 554, wherein the sequences must simultaneously comprise the variable motifs of either SEQ ID NO: 363 or SEQ ID NO: 358; however, both of SEQ ID NOs: 363 and 358 comprise variable “X” residues. This raises a material and substantial issue, which is not addressed, exemplified, or discussed in the originally filed disclosure: how to determine sequence identity of a sequence comprising “X” residues. Variable “X” positions do not count as identities in sequence alignments: Examiner notes that attempts to align variable sequences containing “X” residues using basic alignment tools (e.g., BLAST) yields:
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This result illustrates a nuance of sequence alignments, namely that variable “X” residues are not “identities” because an “identity” requires a single, unique match. Due to this nuance of variable positions and sequence alignments, the correct handling of limitations involving variable residues and sequence identity requirements give rise to indefiniteness issues because claim scope varies depending upon how such limitations interact, which is not clear in view of the art and instant disclosure. As explained above (see, e.g., Rejections of claims 262-269 and 278-285 under 35 USC § 112(b), as set forth above, those discussions are incorporated herein), the interaction of variable positions and sequence identity raises issues of ambiguity. This is pertinent to “possession” under 35 USC 112(a) because the courts have stated that “[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). Here, not “description” is provided in the absence of clarification of how sequence identity is determined with respect to variable residues within the scope of dependent claims 262-269 and 278-285.
Consideration of Alleged Supporting Disclosures
Applicant provides zero supporting disclosures for newly added claims 262-269 and 278-285. Zero literal, implicit, or inherent support was identified commensurate in scope with these claims (see, e.g., Reply filed 10/28/2025, passim). Accordingly, zero evidence of record has been identified by the Applicant supporting a determination that these claims satisfy the written description requirement.
“A written description sufficient to satisfy the requirement of the law requires a statement of an invention, not an invitation to go on a hunting expedition to patch together after the fact a synthetic definition of an invention” (see Indivior UK Ltd. v. Dr. Reddy’s Laboratories S.A., 18 F.4th 1323, 1329 (Fed. Cir. 2021). The courts have noted
As Ruschig makes clear, one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say here is my invention. In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree [*1327] must be in the originally filed disclosure. . . . It is "not a question of whether one skilled in the art might be able to construct the patentee's device from the teachings of the disclosure.... Rather, it is a question whether the application necessarily discloses that particular device. . .
Purdue Pharma LP v. Faulding Inc., 230 F.3d 1320, 1327, 56 U.S.P.Q.2d 1481, 1486, 2000 BL 26918, at *7 (Fed. Cir. 2000)
Here, no “blaze marks” have been identified in the originally filed disclosure, and the originally filed disclosure discloses a “forest”, rather than the “tree” presently claimed.
Conclusion
Per MPEP § 2163, new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement (see, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)). Here, the newly added claim limitations result in a narrower claim genus which defines a novel subgenus of species that was not inherently, implicitly, or literally supported by the originally filed disclosure.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 215-218, 222, 252-273, and 277-286 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 165 and 178 of copending Application No. 18/037,923 (corresponding to US2025/0195673 A1, filed Nov. 30, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other as set forth below.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section, and in preceding rejections. Those interpretations and discussions are incorporated into the instant rejection.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an anticipation analysis.
Claims 165 and 178 of Pro’923 are directed to polypeptides comprising any sequence sharing “at least 90% sequence identity to SEQ ID NO: 187”, among others (see, e.g., Pro’923 at claims 165 and 178; see alternatively US’673 at claims 165 and 178). SEQ ID NO: 187 is understood to be the originally elected species of instant SEQ ID NO: 1:
EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
(compare instant SEQ ID NO: 1 with SEQ ID NO: 187); similarly, instant SEQ ID NO: 2 corresponds to Pro’923 at SEQ ID NO: 400 (compare instant SEQ ID NO: 2 with SEQ ID NO: 400); similarly, instant SEQ ID NO: 3 corresponds to Pro’923 at SEQ ID NO: 401 (compare instant SEQ ID NO: 3 with SEQ ID NO: 401); and instant SEQ ID NO: 554 corresponds to Pro’923 at SEQ ID NO: 233 (compare instant SEQ ID NO: 554 with SEQ ID NO: 233). Accordingly, the originally elected species of SEQ ID NO: 1, and instant SEQ ID NOs: 2-3 and 554 are understood to reasonably read upon and fully satisfy all limitations of instant claims 15-218, 222, 252-273, and 277-286, but such structures were filed and claimed in the claim set of Application No. 18/037,923.
The only ostensible difference is that the copending claims recite and require a “transferrin receptor-binding peptide” having an unspecified, unclaimed structure at claims 165 and 178 of US’923; however, the instant claims are open-ended and may include any structures, including the additional “transferrin receptor-binding peptide” recited by US’923. Accordingly, the copending claims are understood to be species or subgenera within the scope of the genera of the instant claims.
Accordingly, instant claims 215-218, 222, 226-228, and 252-289 are not patentably distinct relative to copending claims 165 and 178 of App’673, because the copending claims recite, claim, and disclose the same structures as instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Both Application were filed 11/29/2021, and have the same patent term filing date.
Response to Arguments
Applicant's arguments filed 4/16/2025 have been fully considered but they are substantially rendered moot in view of the new and revised rejections.
Applicant addresses the prior rejection of claim 217 at pages 8-9 of the Reply (see, e.g., Reply filed 10/28/2025 at 8 at §§ “Claim 217” to page 9 at 1st full ¶). The allegation that “there is no relationship required to be specified between the cysteines of base claim 215 and dependent claim 217” does not reflect the Examiner’s understanding of 35 USC 112(b) or MPEP § 2173, and Applicant fails to provide supporting case law or other legal basis for their position. The rejection of 217 has been revised for clarification as set forth above. As noted above, claim 217 has multiple issues including lack of antecedent basis, relative terminology, and variable structure, which supports a determination of indefiniteness (see, e.g., MPEP § 2173.05(b)(II), noting that when the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite). Accordingly, as explained in the new and revised rejections, it is unclear what embodiments would infringe upon the claim or not, and the courts have stated that “[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, the claim is rejected as indefinite.
Applicant addresses the prior rejection of claim 218 at page 9 of the Reply (see, e.g., Reply filed 10/28/2025 at 9 at §§ “Claim 218”). The amendment relied upon by the Applicant has raised additional issues, as addressed in the new rejections above. Accordingly, the amendment is insufficient to render claim 218 allowable.
Examiner notes: Applicant is advised that pertinent prior art has been cited previously on record (see Pertinent Prior Art section, below). It is noted that examination of the prior art has not been extended to species within the scope of indefinite claims 262-269 and 278-285 at this time.
Regarding the 12/09/2025 interview: Examiner acknowledges that Applicant interview summary filed 1/09/2026, but notes that no alignments or supplemental data was filed prior to the instant examination, which began 1/23/2026.
Examiner notes that Cys placement could likely be clarified simply by reference to SEQ ID NO: 358 (e.g., “A PD-L1-binding peptide comprising SEQ ID NO: 358 [insert sequence as shown at claim 277], wherein the PD-L1-binding peptide further comprises SEQ ID NO: 365 starting at position X32 of SEQ ID NO:358”).
Accordingly, all arguments have been fully considered but not found persuasive for the reasons set forth above. Accordingly, one or more claims remain rejected in view of the new or revised rejections set forth above and necessitated by Applicant’s amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
XP_002949689.1 (NCBI Protein Database, XP_002949689.1, uncharacterized protein VOLCADRAFT_80825 [Volvox carteri f. nagariensis], PLN 13-Aug-2010, also available at https://www.ncbi.nlm.nih.gov/protein/302836257?sat=56&satkey=34081605, (last visited 10/10/2024); cited in previous action) discloses a sequence sharing 85% sequence similarity with instant SEQ ID NO: 1 and sharing 39/49 identities (compare Reference with instant SEQ ID NO: 1). In addition, the sequence shares 93% sequence similarity (46/49) and 90% sequence identity (44/49) with instant SEQ ID NO: 4 (compare Reference with instant SEQ ID NO: 4).
Vaz et al.22 was previously applied as an anticipatory reference on record. Vaz discloses the sequence of Omt-3, which has the sequence of NDPCEEVCIQHTGDVFACLFACQ (see, e.g., Vaz at Table 1 on 5378), which satisfies the structural requirements of instant SEQ ID NO: 361, which corresponds to
[DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKMRLP]C
because the Omt-3 sequence comprises the sequence [T][G][D][V][F][A]C[L][F][A]C (see, e.g., Vaz at Table 1 on 5378; underlined here: NDPCEEVCIQHTGDVFACLFACQ).
El-kereamy et al.23 was previously applied as an anticipatory reference on record. The reference discloses the sequence of PdPR5t, which comprises the sequence of NGKVVACLSAC (see, e.g., Primary Reference at Fig. 2 p. 4 at positions between 170 and 190 for PdPR5t), which satisfies the structural requirements of instant SEQ ID NO: 361, which corresponds to
[DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKMRLP]C
because the prior art sequence comprises [N][G][K][V][V][A]C[L][S][A]C (see, e.g., id.).
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
2 EEDCKVHCVKEWMAGKACAERDKSYTIGRAHCSGQKFDVFKCLDHCAAP
3 EEDCKVHCVKEWMAGKACAERNKSYTIGRAHCSGQKFDVFKCLDHCAAP
4 EEDCKVHCVKEWAAYKACAERIKSYTIGRAHCSGQYFDVWKCLDHCAAP
5 EHDCKVHCVKEWMAGHACAERQKSYTIGRAHCSGQKFDVFKCLDHCAAP
6 KFDVFKCLDHC
7 [KP]F[DK]VF[DK]CL[-C][-C]C; wherein Amino acids within brackets identify alternative possibilities at a single position of the motif, and wherein “-” before a residue within brackets means it is not permitted at the position
8[EMVW][GELF][DES]C[KRV][EQSMLV][DEHKRNQSY]C[DMV][AKRQST][ADEHQSTMILVW][AERQSTWP][AEKRNQTMILVW][GAEKNTY][GADEHKRNQSTMILVWYP][DKRNLV][GADTLWP]C[GAEHKNSFP][GADENP][GDHKRNQSTVY][GDEHKNQSTMIFWYP][GADEHKRNQSYP][GADHNQSVFP][ADHNQSTMIVYP][GADKRTWY][GAENQTIVP][GDNQTLVFP][GAEKRNQSTIYP][ADNI][GDEHNFW]C[GAENSYP][GML][GADKNQW][DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKRMLP]C[GAKSIL][GADERQTF][AHNQSFP]; wherein Amino acids within brackets identify alternative possibilities at a single position of the motif.
9 EEDCKVHCVKEWMAGKACAERQKSYTIGRAHCSGQX1FX2VFX2CLX3X3CAAP has 49 residues, and five variable residues (X1, X2, X2, X3, and X3). So it shares 44/49 identities with instant SEQ ID NO: 1.
10 Vaz et al., Computational design, synthesis, and evaluation of miniproteins as androgen receptor coactivator mimics. Chem Commun (Camb). 2009 Sep 28;(36):5377-9. doi: 10.1039/b910677d. Epub 2009 Aug 17. PMID: 19724790; hereafter “Vaz”, cited in Requirement mailed 5/31/2024.
11 El-kereamy et al., S. Prunus domestica pathogenesis-related protein-5 activates the defense response pathway and enhances the resistance to fungal infection. PLoS One. 2011 Mar 23;6(3):e17973. doi: 10.1371/journal.pone.0017973. PMID: 21448276; PMCID: PMC3063165; hereafter “Elkereamy”; cited in previous action.
12 Although BLAST rounds 44/90 to “90%”, the number is 89.795%, and therefore less than 90% sequence identity as required by the claims.
13 EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP is excluded with the understanding that “XXXXX” is [-A][-E][-R][-Q][-K], wherein “-” excludes an amino acid at a position.
14 Although the BLAST alignment shows “39/49(80%)”, this is an artifact of rounding in the BLAST display. The fraction of 39/40 is 79.59%, and therefore less than 80%.
15 SEQ ID NO:363 is X1FX2VFX2CLX3X3C, wherein X1 is K or P; X2 is D or K; and X3 is anything but Cys. So this genus comprises at least 2*2*2*19*19 species (assuming only 20 proteinogenic amino acids rather than 22), which is 2,888.
16 SEQ ID NO:363 is X1FX2VFX2CLX3X3C, wherein X1 is K or P; X2 is D or K; and X3 is anything but Cys. So this genus comprises at least 2*2*2*19*19 species (assuming only 20 proteinogenic amino acids rather than 22), which is 2,888.
17 EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP is excluded with the understanding that “XXXXX” is [-A][-E][-R][-Q][-K], wherein “-” excludes an amino acid at a position.
18 EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP is excluded with the understanding that “XXXXX” is [-A][-E][-R][-Q][-K], wherein “-” excludes an amino acid at a position.
19 A 49-mer with 43 variable residues: [EMVW][GELF][DES]C[KRV][EQSMLV][DEHKRNQSY]C[DMV][AKRQST][ADEHQSTMILVW][AERQSTWP][AEKRNQTMILVW][GAEKNTY][GADEHKRNQSTMILVWYP][DKRNLV][GADTLWP]C[GAEHKNSFP][GADENP][GDHKRNQSTVY][GDEHKNQSTMIFWYP][GADEHKRNQSYP][GADHNQSVFP][ADHNQSTMIVYP][GADKRTWY][GAENQTIVP][GDNQTLVFP][GAEKRNQSTIYP][ADNI][GDEHNFW]C[GAENSYP][GML][GADKNQW][DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKRMLP]C[GAKSIL][GADERQTF][AHNQSFP]
20 A 49-mer with 43 variable residues: [EMVW][GELF][DES]C[KRV][EQSMLV][DEHKRNQSY]C[DMV][AKRQST][ADEHQSTMILVW][AERQSTWP][AEKRNQTMILVW][GAEKNTY][GADEHKRNQSTMILVWYP][DKRNLV][GADTLWP]C[GAEHKNSFP][GADENP][GDHKRNQSTVY][GDEHKNQSTMIFWYP][GADEHKRNQSYP][GADHNQSVFP][ADHNQSTMIVYP][GADKRTWY][GAENQTIVP][GDNQTLVFP][GAEKRNQSTIYP][ADNI][GDEHNFW]C[GAENSYP][GML][GADKNQW][DEHKNQSTLVFYP][GEQF][DK][GVP][GHRVFWP][ADK]C[EHQLF][DERSTMLF][GADEHKRMLP]C[GAKSIL][GADERQTF][AHNQSFP]
21 EEDCKVHCVKEWMAGKACXXXXXSYTIGRAHCSGQXFXVFXCLXXCAAP, with the understanding that “XXXXX” is [-A][-E][-R][-Q][-K], wherein “-” excludes an amino acid at a position.
[3] See, e.g., Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1349, 107 U.S.P.Q.2d 1457, 1467, 2013 BL 192990, 14 (Fed. Cir. 2013), explaining that the written description analysis requires “[t]aking each claim . . . as an integrated whole rather than as a collection of independent limitations”.
22 Vaz et al., Computational design, synthesis, and evaluation of miniproteins as androgen receptor coactivator mimics. Chem Commun (Camb). 2009 Sep 28;(36):5377-9. doi: 10.1039/b910677d. Epub 2009 Aug 17. PMID: 19724790; hereafter “Vaz”, cited in Requirement mailed 5/31/2024.
23 El-kereamy et al., S. Prunus domestica pathogenesis-related protein-5 activates the defense response pathway and enhances the resistance to fungal infection. PLoS One. 2011 Mar 23;6(3):e17973. doi: 10.1371/journal.pone.0017973. PMID: 21448276; PMCID: PMC3063165; hereafter “Elkereamy”; cited in previous action.