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 1-3 and 40-43 are pending. Claims 4-39 were canceled; claims 40-43 were newly added; and claims 1 and 2 were amended in the Reply filed 7/21/2026. Claim 42 is withdrawn as directed to a non-elected invention. Claims 1-3, 40-41, and 43 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (affinity polypeptides, original claims 1-19) and the species of SEQ ID NO: 3 in the reply filed on 1/14/2026 is acknowledged.
The originally elected species of SEQ ID NO: 3 has the following sequence:
AVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCAVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCAVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSK
The highlighted text represents subunits of SEQ ID NO: 17, wherein SEQ ID NO: 17 is
FNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDD.
The underlined portions represent instant SEQ ID NO: 19 (AVAQS), and the remainder represents SEQ ID NO: 18, which is
FNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC.
The originally elected species is understood to read upon instant claims 1-4, but not claims 5-19 (see, e.g., Reply filed 1/14/2026 at 2 at 2nd ¶).
Following extensive search and examination, the originally elected species consisting of SEQ ID NO: 3 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to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration.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 extended to a non-elected species consisting of SEQ ID NOs: 1-2 and 4-16, which were all subsequently deemed free of the prior art. Therefore, compounds consisting of one of SEQ ID NOs: 1-16 are each free of the prior art.
Examination was then extended to non-elected species sharing 90% sequence identity with instant SEQ ID NO: 3, and species within this subgenus were examined and deemed obvious for reasons of record (see, e.g., Action mailed 3/16/2026 at pages 16-23).
In the Reply filed 7/21/2026, Applicant amended the claims to exclude the previously examined embodiments sharing 90% sequence identity with instant SEQ ID NO: 3. Accordingly, examination has been extended to all species sharing 97% sequence identity or greater with instant SEQ ID NOs: 1-16, which have all been deemed free of the prior art.
Accordingly, claim 40 is in form for allowance. However, claims 1-3, 41, and 43 remain rejected under 35 USC § 112, and therefore are not currently in form for allowance.
Claim 42 is 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. Election was made without traverse in the reply filed on 1/14/2026.
Claims 1-3, 40-41, and 43 are presently examined.
Priority
The priority claim to Provisional 62/971509 (filed 2/07/2020) is acknowledged.
Information Disclosure Statement
No IDS was filed 7/21/2026.
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).
Claim 1 is representative of the pending claim scope and the applicable claim interpretation is discussed below.
Amended claims 1 and 43 recite the term “about”, which is undefined on record. The term “about” lacks an exact meaning in the prior art and may reasonably mean ±5%, ±10%, ±20%, within “5-fold of a value” or even “within an order of magnitude”, etc. (see, e.g., US8008449B21 at col. 18 at lines 19-33, noting that “particularly with respect to biological systems or processes, [about] can mean up to an order of magnitude or up to 5-fold of a value”; see also US20180162942A12 at ¶[0108], defining “about” to include an order of magnitude or 5-fold of a value).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
All prior rejections are withdrawn in view of the amendments to claims 1 and 3, cancellation of claims 4-39, and addition of new claims 40-43. However, the amendments and newly added claims have necessitated new rejections as set forth below.
New or Revised Claim Rejections Necessitated by Applicant Amendment
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 1-3, 41, and 43 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.
[35 USC 112(b), Issue 01]
Amended claim 1 now recites “wherein Subunit-1 has at least 97% identity to SEQ ID NO: 17”, which renders the claim scope indefinite. SEQ ID NO: 17 is
FNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDD
Accordingly, SEQ ID NO: 17 is 33 amino acids in length, which means that a single mismatch with SEQ ID NO: 17 yields only 32/33 identities, which is 96.9696% identity, which is never literally within the range of “at least 97% identity to SEQ ID NO: 17”. This raises substantial indefiniteness issues because it is unclear how such sequence identity limitation should be reasonably interpreted:
First, Applicant may mean to define “percent sequence identity” normally, but simply round up to the nearest whole percentage (i.e., 96.9696% would become 97%, permitting a single mismatch with instant SEQ ID NO: 17); this is pertinent because it would mean that the difference between SEQ ID NO: 17 and 18 at claim 1 is arbitrary since SEQ ID NO: 17 shares 96.9696% sequence identity with instant SEQ ID NO: 18:
PNG
media_image1.png
91
483
media_image1.png
Greyscale
;
Second, Applicant may mean to define “percent sequence identity” normally, but intends to exclude all sequences that are not literally “at least 97% identical to SEQ ID NO: 17”, which would mean the added language of “at least 97% identical” was superfluous and non-limiting since only the single sequence sharing 100% identity with SEQ ID NO: 17 is included in the claim scope;
Third, Applicant means to define “percent sequence identity” in a different, but undisclosed and undefined manner, inconsistent with its normal usage in the art, which would permit calculations of fractional percent identity with individual amino acids.
Therefore, the reference to “97% identity to SEQ ID NO: 17”, raises interpretation concerns, because multiple potential interpretations exist, but the metes and bounds of the pending claim scope are ambiguous. Furthermore, close prior art exists (see, e.g., Action mailed 3/16/2026 at pages 16-23). For purposes of applying prior art, the claim has been interpreted literally (second option, above) to require a minimum of 97.0000% sequence identity, which excludes even a single mismatch since 32/33 is 96.9696%. This is reasonable, because no specialized meaning of sequence identity has been set forth on record consistent with the first or third interpretations. Applicant may address this rejection by amending claim 1 and simply replacing the phrase “has at least 97% identity to SEQ ID NO: 17” with “is SEQ ID NO: 17” at lines 2-3 of instant claim 1. However, Applicant is advised that such an amendment would necessitate an objection of claim 43 as a substantial duplicate claim (see, e.g., MPEP § 608.01(m) at form paragraphs 7.05.05 and 7.05.06), and therefore such an amendment to overcome this rejection should be accompanied by cancellation of claim 43.
[35 USC 112(b), Issue 02]
Amended claim 1 and newly added claim 43 are indefinite in view of the variable nature of Subunit-2 as recited at the claims, which permits distinct interpretations, and raises multiple issues, including lack of antecedent basis and unclear claim scope regarding potentially excluded embodiments3. Amended claim 1 and newly added claim 43 each recite
…wherein Subunit-2 has at least 97% identity to SEQ ID NO: 18, wherein residues at positions 5 and 34 of Subunit-2 are cysteine, wherein there is a disulfide bond between the two cysteine residues…
This language raises interpretation issues because SEQ ID NO: 18 is a 34-mer sequence comprising two cysteines:
FNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC
However, the newly amended claim scope permits a single mismatch (e.g., 33/34 is 97.06% identity), wherein the mismatched residue may presumably be a cysteine. For example, the following sequence shares 97.06% identity with instant SEQ ID NO: 18:
FNMQCQRRFYEALHCPNLTEEQRNAKIQSIRDDC4
Alternatively, Subunit-2 may contain a single deletion relative to SEQ ID NO: 18 (e.g., a single deletion would yield 33/34 matches, which is 97.06% identity), wherein the deleted residue may be a cysteine. Accordingly, the claim scope presumably includes embodiments wherein Subunit-2 may be a 33-mer deletion variant, such as:
NMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC5, or
FNMQQRRFYEALHDPNLTEEQRNAKIQSIRDDC6
Alternatively, Subunit-2 may contain a single addition mutation relative to SEQ ID NO: 18 (e.g., a single addition would yield 34/35 matches, which is 97.14% identity), wherein the added residue may be a cysteine. Accordingly, the claim scope presumably includes embodiments wherein Subunit-2 may be an addition variant and 35-mer, such as:
FCNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC,
FNMQCCQRRFYEALHDPNLTEEQRNAKIQSIRDDC,
FNMQCQRRFYEALHDCPNLTEEQRNAKIQSIRDDC, or
FNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCC
Each of these sequences are presumably permissible as Subunit-2 because they each share at least 97.14% identity (34/35) with instant SEQ ID NO: 18. However, added residues create an antecedent basis issue, because cysteine residues are not necessarily located at positions “5 and 34 of Subunit-2” in such embodiments, but rather potentially at (i) positions 6 and 35, (ii) positions 5 and 35, (iii) positions 5-6 and 35, (iv) positions 5, 16, and 35, (v) positions 5, 34, and 35, etc., etc. Similar position issues arise in deletion variants that are encompassed within the definition of Subunit-2 at instant claim 1. In sum, considering the variable nature of Subunit-2 in combination with subsequent references to structures of Subunit-2, it is unclear
(a) if claim 1 excludes all mismatch, addition, or deletion variants of Subunit-2 sharing 97% identity with instant SEQ ID NO: 18 that result in a Subunit-2 having cysteines present at positions other than 5 and 34 of Subunit-2;
(b) if claim 1 excludes all mismatch or addition variants of Subunit-2 sharing 97% identity with SEQ ID NO: 18 that result in a Subunit-2 that contains more than “two cysteine residues”; or
(c) if claim 1 includes all possible variants of Subunit-2 sharing 97% identity with SEQ ID NO: 18, but wherein the limitations of claims 1 and 43 should be interpreted as relative to unmodified SEQ ID NO: 18 instead of Subunit-2 (e.g., “one to ten of Subunit-2, wherein Subunit-2 has at least 97% identity to SEQ ID NO: 18, wherein the cysteine residues at positions 5 and 34 relative to SEQ ID NO: 18 are present in Subunit-2 and are connected by a disulfide bond ”, which limits the references to cysteine to be relative to SEQ ID NO: 18 rather than the resulting Subunit-2).
Accordingly, given the variability of Subunit-2, but subsequent references to specific positions of Subunit-2 that may or may not exist, or otherwise specific references potentially lacking antecedent basis in some embodiments (e.g., “the two cysteines”), it is prima facie unclear what the metes and bounds of Subunit-2 at claims 1 and 43 may be (see also MPEP § 2173.05(b)(II), discussing how references to variable objects may render a claim indefinite). Therefore, claims 1 and 43 are rejected as indefinite.
[35 USC 112(b), Issue 03]
Amended claim 1 and newly added claim 43 recite a variable length structure (the minimal structure must comprise two of one subunit and at least one of the other, and is therefore ~100 residues, and ten of each would yield ~670 residues, but may be much longer depending upon the spacer described at claim 2 and the meaning of “about”), comprising a variable structure of Subunit-2 (see discussions in preceding paragraphs), and now recites and requires a variable structural limitation, namely that “there is one disulfide bond for every about 80-125 amino acid residues”. These variable limitations based upon variable structures permit distinct interpretations that raise concerns regarding included and excluded embodiments. The issue created by the variable references to a variable structure may be illustrated by reference to the following structures, lengths of each structure, and hypothetical number of disulfide bonds present in each structure:
(1) (Subunit-1)-(Subunit-2)-(Subunit-1) [Length ~100; 1 bond]
(2) (Subunit-2)-(Subunit-1)-(Subunit-2) [Length ~101; 2 bonds]
(3) (Subunit-1)10-(Subunit-2) [Length ~364; 1 bond]
(4) (Subunit-2)-(Subunit-1)10, [Length ~364; 1 bond]
(5) (Subunit-2)-(Subunit-1)10-(Subunit-2) [Length ~398; 2 bonds]
(6) (Subunit-2)-(Subunit-1)5-(Subunit-2)-(Subunit-1)3 [Length ~332; 2 bonds]
(7) (Subunit-2)-(Subunit-1)5-(Subunit-2)-(Subunit-1)2 [Length ~299; 2 bonds]
(8) (Subunit-2)-(Subunit-1)5-(Subunit-2)-(Subunit-1)1 [Length ~266; 2 bonds]
(9) (Subunit-2)-(Subunit-1)5-(Subunit-2) [Length ~233; 2 bonds]
(10) (Subunit-2)-(Subunit-1)5 [Length ~200; 1 bond]
The indefiniteness issue may simply be encapsulated by the question “which of these are included or excluded by claims 1 and 43?” Notably, the phase “for every about 80-125 amino acid residues” raises immediate concern regarding the meaning of “about”, which is not defined on record and lacks any specific meaning in the art for this particular context; however, “about” may reasonably mean ±5%, ±10%, ±20%, within “5-fold of a value” or even “within an order of magnitude”, etc. (see, e.g., US8008449B27 at col. 18 at lines 19-33; see also US20180162942A18 at ¶[0108], defining “about” to include an order of magnitude or 5-fold of a value). This is pertinent because
If “about” were considered to mean an order of magnitude then the range would be “for every 8-1250 amino acids”, and each of structures (1)-(10) would be included.
However, if “about” were considered to mean ±20%, then the range would be “for every 64 to 150 amino acids”, which would presumably exclude structures (3)-(6) and (10), but read upon structures (1)-(2) and (7)-(9).
However, if “about” were considered to mean ±10%, then the range would be “for every 72 to 137.5 amino acids”, which would presumably exclude structures (3)-(7) and (10), but read upon structures (1)-(2) and (8)-(9).
However, if “about were considered to mean ±5%, then the range would be “for every 76 to 131.25 amino acids”, which would presumably exclude structures (3)-(8) and (10), but read upon structures (1)-(2) and (9).
Accordingly, the usage of an ill-defined and variable range to refer to an ill-defined and variable structure raises substantial and material concerns regarding the metes and bounds of the pending claim scope that permits multiple interpretations (see also MPEP § 2173.05(b)(II), discussing how references to variable objects may render a claim indefinite). Accordingly, an artisan would not know how to avoid infringement of the pending claim scope. Accordingly, claims 1 and 43 are rejected as indefinite.
[35 USC 112(b), Issue 04]
Amended claim 1 and newly added claim 43 recite the functional limitation
…wherein there is one disulfide bond for every about 80-125 amino acid residues of the affinity polypeptide ligand…
This is a functional limitation because the same, exact polypeptide sequence may have 0, 1, 2, or more disulfide bonds dependent upon the specific oxidizing environment (see, e.g., Góngora-Benítez et al.9 at 905-906 at bridging ¶, 907 at col I-II at bridging ¶, 907 at Fig. 7, explaining that disulfide bond formation is dependent upon temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent, wherein intramolecular disulfide formation requires the use of dilute peptide concentrations “to prevent accumulation of oligomeric byproducts”). This issue can be illustrated by reference to the following structures, length, hypothetical number of disulfide bonds present in each structure, and the environment:
(1) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 0 bonds; strong reducing]
(2) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 1-2 bonds; weak oxidizing]
(3) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 3-4 bonds; oxidizing]
(4) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 5-10 bonds; strongly oxidizing]
Assuming each of (1)-(4) have the identical sequence structure, and differ only with respect to the specific oxidizing environment (e.g., temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent). Accordingly, (1) would be excluded and (3) would be included from the claim scope by the functional limitation, and species of (2) and (4) may be included or excluded by the claim scope, dependent upon the interpretation of “about” (see discussion in preceding paragraph). However, for purposes of the instant rejection, the illustrated structures exemplify the relevant point, namely that the “wherein” clause amounts to a functional limitation that functionally limits the temperature, pH, peptide concentration, and ionic strength of the claimed compound, but in an unknown manner. Critically, the functional limitation fails to correspond to any structure/function relationship of record. This is pertinent because, per MPEP § 2173.05(g),
[T]he 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. . .
Here, the claims merely recite a description of a desired result to be achieved (i.e., a particular number of disulfide bonds) rather than a description of the actual structures and environment (e.g., temperature, pH, concentrations, etc.) required to actually achieve the desired result and functional outcome, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what compound formulations do or do not infringe upon the scope of claims 1 and 43. Notably, the courts have stated that
Regardless 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, because it is unclear what compound formulations of the variable structures as claimed do or do not satisfy the functional limitations of claims 1 and 43 with respect to disulfide bonds, an artisan would be unable to identify infringing from non-infringing compounds, and therefore claims 1 and 43 are rejected as indefinite.
[35 USC 112(b), Issue 05]
At claims 1 and 43, the claims recite a “wherein” clause at the final line reciting “wherein the disulfide bonds . . .”, which renders the claim scope indefinite because “disulfide bonds” is plural, and therefore it is unclear if the claimed structures require a minimum of two disulfide bonds, excluding embodiments having a single disulfide bond. This issue may be illustrated by reference to the following structures, lengths of each structure, and hypothetical number of disulfide bonds present in each structure:
(1) (Subunit-1)-(Subunit-2)-(Subunit-1) [Length ~100; 1 bond]
(2) (Subunit-2)-(Subunit-1)-(Subunit-2) [Length ~101; 2 bonds]
If the “wherein” clause limits the claim structures to structures comprising at least two disulfide bonds, compounds such as (1) would be excluded from the pending claim scope. However, if the “wherein” clause is merely a recitation of intended and expected results, then presumably (1) would not be excluded from the pending claim scope. Accordingly, because there are different plausible constructions, and it is unclear which is correct, claims 1 and 43 are rejected as indefinite as an artisan would not be reasonably apprised of what does or does not infringe upon the pending claim scope.
[35 USC 112(b), Issue 06]
At amended claim 1 and newly added claim 43, the claims recite the phrase
…wherein the disulfide bonds enhance the helical structure of the affinity polypeptide ligand.
This phrase renders the claim scope indefinite because it is unclear if (i) the “wherein” clause is merely a recitation of intended and expected results (e.g., non-limiting), or (ii) if the “wherein” clause is a functional limitation that require disulfide bonds that specifically “enhance the helical structure”, while excluding all other disulfide bonds that do not “enhance the helical structure”. As an initial matter, because there are two different interpretations and plausible constructions, the claim is indefinite. However, even if the “wherein” clause is intended to be a functional limitation, it remains indefinite because it is prima facie unclear which potential disulfide bonds between a residue 5 and a residue 34 of a Subunit-2 moiety do or do not “enhance the helical structure” as required by claims 1 and 43. This is pertinent because the polypeptides comprising multiple cysteine residues can form different heterogenous and intermediate structures differing by disulfide bond linkages (see, e.g., Arolas et al.10 at title, abs, Box 1 on 283, Fig. 1 on 295), and the formation of specific disulfide bonds depends on environmental parameters (see, e.g., Góngora-Benítez et al.11 at 905-906 at bridging ¶, 907 at col I-II at bridging ¶, 907 at Fig. 7, explaining that disulfide bond formation is dependent upon temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent, wherein intramolecular disulfide formation requires the use of dilute peptide concentrations “to prevent accumulation of oligomeric byproducts”). Therefore, the issue hinges on the existence of cysteine pairing heterogeneity, disulfide intermediates, and general conformational diversity. This issue may be illustrated by considering the following three structures, which are of identical length, identical sequence composition, and only differ by the specific disulfide bonds formed between positions 5 and 34 of Subunit-2:
PNG
media_image2.png
516
642
media_image2.png
Greyscale
It is unclear if all disulfide bonds shown do or do not “enhance the helical structure” as required by amended claim 1 and newly added claim 43, although all dotted lines represent a disulfide bond between a position 5 and position 34 residue of a Subunit-2 moiety. This is pertinent because, per MPEP § 2173.05(g),
[T]he 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. . .
Here, the claims merely recite a “wherein” clause that describes a desired result to be achieved (i.e., “enhancement” of a “helical structure”), rather than a description of the actual structures (i.e., specific disulfide bonds that do enhance helical structure) and the environment (e.g., temperature, pH, concentrations, etc.) required to actually achieve the desired result and functional outcome; therefore, the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what compound formulations do or do not infringe upon the scope of claims 1 and 43 because it is unclear what disulfide bond arrangements do or do not “enhance helical stability”. Notably, the courts have stated that
Regardless 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, because it is unclear what compound formulations of the variable structures as claimed do or do not satisfy the functional limitations of claims 1 and 43 with respect to disulfide bonds, an artisan would be unable to identify infringing from non-infringing compounds, and therefore claims 1 and 43 are rejected as indefinite12.
[35 USC 112(b), Issue 07]
Amended claim 1 and newly added claim 43 recite a variable limitation, namely that “there is one disulfide bond for every about 80-125 amino acid residues”, wherein the structure of claims 1 and 43 is not completely defined because it has an unknown length and composition (see, e.g., instant claim 2, noting that the spacer compositions and spacer length at claims 1 and 43 is unlimited); this means that claim 1, as presently drafted reads upon variable structures having variable lengths, such as
Lx-(Subunit-1)-Lx-(Subunit-2)-Lx-(Subunit-1)-Lx
Wherein “Lx” represents an optional N-trailer, C-trailer, or spacer sequence of variable length “x”. This is pertinent because an embodiment may be included or excluded from the scope of claim 1 depending upon the unknown and variable length of Lx. This issue may be illustrated as shown below:
(Subunit-1)-L0-(Subunit-2)-L0-(Subunit-1) [Length ~100; 1 bond]
(Subunit-1)-L20-(Subunit-2)-L20-(Subunit-1) [Length ~140; 1 bond]
(Subunit-1)-L50-(Subunit-2)-L50-(Subunit-1) [Length ~200; 1 bond]
All examples show identical subunit structures and arrangements, differing only by the length of two spacer units of “L0”, “L20”, and “L50”, which are zero, twenty, or fifty amino acids in length, respectively. Although the first embodiment is included in the scope of claim 1, the third embodiment is not; furthermore, the second embodiment is presumably excluded, but may be included depending upon the meaning of “about”. Here, the spacer and trailer sequence placement and length is unbounded and unspecified by instant claim 1, and therefore the total length of an embodiment is unknown, unspecified, and variable at claim 1. Accordingly, whether or not embodiments satisfy claim 1 and the variable range limitation requiring that “there is one disulfide bond for every about 80-125 amino acid residues”, depends upon the unknown and variable length of spacer and trailer sequences, which have unknown and unspecified total lengths. Accordingly, the use of a variable range limitation (“about 80-125 amino acid residues”) in combination with a variable structure and length, render the scope of claim 1 indefinite (see MPEP § 2173.05(b)(II), discussing how references to variable objects may render a claim indefinite).
[35 USC 112(b), Issue 08]
Claim 41 recites the phrase “at least 97% identity to:” followed by a recitation of sequences followed by a clause “having a disulfide bond between cysteine residues at positions…..”. This construction renders the claim indefinite because it is unclear if the “clause” following each SEQ ID NO: is merely descriptive of the sequence being referenced, or if the “clause” is a structural limitation that must be present and shared by all variants sharing 97% sequence identity with a recited SEQ ID NO. Therefore, whether or not the clause is limiting or merely descriptive alters the claim scope because it changes whether or not such positions can be mutated or altered by insertions or deletions is unclear for reasons similar to those discussed at “Issue 02”, above (that discussion is incorporated herein), or if such insertions or deletions altering the position of such cysteines are excluded from the claim scope (e.g., an insertion at position 1 would cause all positions to be shifted by one). Accordingly, claim 41 is rejected as ambiguous.
[Summary]
Claims 2-3 depend directly or indirectly from an indefinite claim, and fail to clarify the indefiniteness of the claim upon which it depends. Accordingly, claims 2-3 are rejected as indefinite.
Claims 1-3, 41, and 43 are rejected as indefinite.
Claim Rejections - 35 USC § 112(a), New Matter
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.
Claim 41 is 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.
Claim Scope
Claim 41 is directed to sixteen different subgenera of affinity polypeptide ligands, sharing at least 97% sequence identity with an individual sequence selected from SEQ ID NOs: 1-16. The applicable claim interpretations have been set forth above under 35 USC 112(b) and in a separate claim interpretation section. Those discussions are incorporated herein.
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.
No literal support exists for new claim 41 as filed 7/21/2026.
Zero identification of any disclosure defining a subgenus sharing 97% sequence identity with multiple sequences as recited at newly added claim 41 appear in the originally filed disclosure.
Accordingly, claim 41 lacks literal support 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 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 instantly amended claim scope. Accordingly, the amendments cannot be said to correct an “obvious error”.
Here, zero implicit or inherent support for the pending claim scope appears on record at least because “97% identity” is only mentioned in the original disclosure with respect to SEQ ID NOs: 17, 18, and 19 (see, e.g., Spec. filed 9/13/2022 at 4 at lines 11-16, 5 at lines 7-11), and was not present in the originally filed disclosure or originally filed claims.
In addition, original claims 1 and 4-19 are the most similar to newly added claim 41. However, these claims are directed to a substantially broader and more highly varied genus of species comprising sequences sharing only 90% sequence identity, rather than the substantially narrower subgenera sharing 97% identity as recited at newly added claim 1. 90% and 97% are not synonymous or equivalent, and therefore claim 41 does not find support in the originally filed claims.
Applicant Cited Support
Applicant failed to identify any supporting disclosure commensurate in scope with newly added claim 41 in the reply filed 7/21/2026. Accordingly, such language appears to lack any inherent, implicit, or literal support in the originally filed disclosure.
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 are not inherently, implicitly, or literally supported by the originally filed disclosure.
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). Likewise, in the instant case, the claims are directed to methods of treating a functionally defined genus of diseases using unknown amounts of untested compounds, and have only identified generically “goals [Applicant] hope the claimed invention achieves”, and left it completely to others to actually invent and discover the specifics of the methods Applicant has attempted to claim.
Accordingly, claim 41 is rejected as directed to new matter.
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 1-3 and 43 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.
The legal analysis for determining whether or not a disclosure satisfies the written description requirement is set forth at MPEP § 2163.
The relevant issues have been raised under 35 USC 112(b) above, and those discussions regarding functional limitations are incorporated into the instant rejection. Specifically, amended claim 1 and newly added claim 43 recite functional limitations:
A. At claim 1, “97% identity to SEQ ID NO: 17” is undefined on record because it is a 33-mer and 32/33 identities is less than 97%. Therefore, it is unclear how percent identity is being determined to include fractional portions of amino acids.
B. At claims 1 and 43, the phrase “wherein there is one disulfide bond for every about 80-125 amino acid residues of the affinity polypeptide ligand” is a functional limitation impacting the pH, temperature, solvent conditions, peptide concentrations, etc. of the claimed products, but in an unknown manner that is not described on record in a manner commensurate in scope with the instant claim scope.
C. At claims 1 and 43, the phrase “wherein the disulfide bonds enhance the helical structure of the affinity polypeptide ligand” is understood to be a functional limitation impacting the specific bond arrangements that are permitted, wherein particular bond arrangements are reasonably presumed to require particular oxidizing environments that are not described on record commensurate in scope with the pending claim scope.
Regarding the “97% identity to SEQ ID NO: 17”, Amended claim 1 now recites “wherein Subunit-1 has at least 97% identity to SEQ ID NO: 17”, which renders the claim scope indefinite. SEQ ID NO: 17 is
FNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDD
Accordingly, SEQ ID NO: 17 is 33 amino acids in length, which means that a single mismatch with SEQ ID NO: 17 yields only 32/33 identities, which is 96.9696% identity, which is never within the range of “at least 97% identity to SEQ ID NO: 17”. This raises substantial description concerns because percent sequence identity is defined in the art as requiring an identical amino acid as a whole, and is not defined in a fractional manner. Therefore, it is unclear if such language is non-limiting and superfluous, or if the Applicant has attempting to redefine the meaning of “percent identity” to include fractional relationships of less than one whole amino acid. However, no description is provided on record or in the prior art that provides clear meaning to a limitation requiring at least 97% identity with a 33-mer residue. Accordingly, presumably such language defines a subgenus consisting of a single species, namely instant SEQ ID NO: 17.
Regarding the phrase “wherein there is one disulfide bond for every about 80-125 amino acid residues of the affinity polypeptide ligand”, this is understood to be an ill-defined functional limitation because the same, exact polypeptide sequence may have 0, 1, 2, or more disulfide bonds dependent upon the specific oxidizing environment (see, e.g., Góngora-Benítez et al.13 at 905-906 at bridging ¶, 907 at col I-II at bridging ¶, 907 at Fig. 7, explaining that disulfide bond formation is dependent upon temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent, wherein intramolecular disulfide formation requires the use of dilute peptide concentrations “to prevent accumulation of oligomeric byproducts”). This issue can be illustrated by reference to the following structures, length, hypothetical number of disulfide bonds present in each structure, and the environment:
(1) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 0 bonds; strong reducing]
(2) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 1-2 bonds; weak oxidizing]
(3) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 3-4 bonds; oxidizing]
(4) [(Subunit-1)-(Subunit-2)]5 [Length ~335; 5-10 bonds; strongly oxidizing]
Assuming each of (1)-(4) have the identical sequence structure, and differ only with respect to the specific oxidizing environment (e.g., temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent). Accordingly, (1) would be excluded and (3) would be included from the claim scope by the functional limitation, and species of (2) and (4) may be included or excluded by the claim scope, dependent upon the interpretation of “about” (see discussions above under 35 USC 112(b)). However, for purposes of the instant rejection, the illustrated structures exemplify the relevant point, namely that the “wherein” clause amounts to a functional limitation that functionally limits the temperature, pH, peptide concentration, and ionic strength of the claimed compound, but in an unknown manner. Critically, the functional limitation fails to correspond to any structure/function relationship of record. This is pertinent because, the claims merely recite a description of a desired result to be achieved (i.e., a particular number of disulfide bonds) rather than a description of the actual structures and environment (e.g., temperature, pH, concentrations, etc.) required to actually achieve the desired result and functional outcome, and therefore the claims are not properly defined. Notably, the courts have stated that
Regardless 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, because it is unclear what compound formulations of the variable structures as claimed do or do not satisfy the functional limitations of claims 1 and 43 with respect to disulfide bonds, an artisan would be unable to identify infringing from non-infringing compounds, and therefore claims 1 and 43 are rejected as indefinite. Accordingly, it is unclear what specific ranges of pH, temperature, solvent, salts, peptide concentrations, etc. are required to achieve the functional limitation.
Regarding the phrase “wherein the disulfide bonds enhance the helical structure of the affinity polypeptide ligand”, for purposes of this rejection, this language is understood to be a functional limitation that limits the specific spacing and specific cystine pairings included and excluded by the instant claim scope. It is prima facie unclear which potential disulfide bonds between a residue 5 and a residue 34 of a Subunit-2 moiety do or do not “enhance the helical structure” as required by claims 1 and 43. This is pertinent because the polypeptides comprising multiple cysteine residues can form different heterogenous and intermediate structures differing by disulfide bond linkages (see, e.g., Arolas et al.14 at title, abs, Box 1 on 283, Fig. 1 on 295), and the formation of specific disulfide bonds depends on environmental parameters (see, e.g., Góngora-Benítez et al.15 at 905-906 at bridging ¶, 907 at col I-II at bridging ¶, 907 at Fig. 7, explaining that disulfide bond formation is dependent upon temperature, pH, peptide concentration, ionic strength, and the presence of oxidizing reagent, wherein intramolecular disulfide formation requires the use of dilute peptide concentrations “to prevent accumulation of oligomeric byproducts”). Therefore, the issue hinges on the existence of cysteine pairing heterogeneity, disulfide intermediates, and general conformational diversity. This issue may be illustrated by considering the following three structures, which are of identical length, identical sequence composition, and only differ by the specific disulfide bonds formed between positions 5 and 34 of Subunit-2:
PNG
media_image2.png
516
642
media_image2.png
Greyscale
It is unclear if all disulfide bonds shown do or do not “enhance the helical structure” as required by amended claim 1 and newly added claim 43, although all dotted lines represent a disulfide bond between a position 5 and position 34 residue of a Subunit-2 moiety. This is pertinent because, the claims merely recite a “wherein” clause that describes a desired result to be achieved (i.e., “enhancement” of a “helical structure”), rather than a description of the actual structures (i.e., specific disulfide bonds that do enhance helical structure) and the environment (e.g., temperature, pH, concentrations, etc.) required to actually achieve the desired result and functional outcome; therefore, it is prima facie unknown what exact disulfide bond arrangements do or do not “enhance helical stability”. Notably, the courts have stated that
Regardless 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, because it is unclear what compound formulations of the variable structures as claimed do or do not satisfy the functional limitations of claims 1 and 43 with respect to disulfide bonds, an artisan would be unable to identify infringing from non-infringing compounds, and therefore this limitation is not adequately described on record.
Regarding teachings of record and reductions to practice, the functionality required to constitute an “affinity polypeptide ligand” is not specifically disclosed in a structure/function relationship commensurate in scope with the instant claims on record, but the term is understood to include sequences that “specifically binds analytes, e.g., immunoglobulin proteins” (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25-31), and sequences having “superior affinity for analytes, while providing stability of a ligand over a wide pH range (3-13)” (see, e.g., Spec. filed 9/13/2022 at 4 at lines 20-21), and sequences capable of use in a solid support having a “capacity of greater than about 30 g/L” (see, e.g., Spec. filed 9/13/2022 at 10 at lines 15-21). However, it is prima facie unclear which exact structures from among all of those claimed do or do not act as an “affinity polypeptide ligand” as required by the claim scope, or otherwise satisfy the newly added functional limitations discussed above.
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. Notably, the disclosure appears to test and reduce to practice a single sequence with specificity, that was shown to have the required functionality, namely instant SEQ ID NO: 3 (see, e.g., Spec. filed 9/13/2022 at 3 at lines 1-15, Figs. 1-4). Additional sequences were disclosed on record, but do not appear to have been specifically tested (e.g., instant SEQ ID NOs: 1-2 and 4-16). Even assuming arguendo that each of SEQ ID NOs: 1-16 were “affinity polypeptide ligands” having the requisite functionality, each of these sequences comprise repeats consisting only of sequences comprising instant SEQ ID NOs: 17, 18, and 19 without any variation. Therefore, even if the limited testing was extended to all explicitly disclosed sequences, the instant disclosure fails to provide any additional guidance regarding what structures and variations are permissible within such sequences without abrogating the required functionality. 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 embodiments lacking 100% sequence identity to instant SEQ ID NOs: 17, 18, and 19 does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed 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. Here, the Specification identifies that the claimed structures contain cysteine amino acids, and that “[t]he cysteine amino acids which form a disulfide bond are typically about 28 amino acid residues apart from one another”, that “there is about one disulfide bond for every about 80-125 amino acids of a ligand”, and that “disulfide bonds stabilize the helical nature of the polypeptide ligand” (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25 to page 4 at line 10). Critically, such limitations are not actually recited in the pending claims, which actually do not limit cysteine amino acids from being directly adjacent to one another or otherwise within more or less than 28 amino acids (compare id. with instant claims 1-3 and 43, noting that sequence identity does not limit the placement of cysteine substitutions or insertions).
The functional limitations recited at the newly added “wherein” clauses do not correspond to any structure/function relationship of record commensurate in scope with the claims, but rather these functional limitations appear to be repeated only as something that the inventors hope and desire to achieve (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25-31, disclosing hoped-for result, namely sequences having “superior affinity for analytes, while providing stability of a ligand over a wide pH range (3-13)”; see, e.g., Spec. filed 9/13/2022 at 4 at lines 20-21, disclosing a hoped for result with no structure/function relationship).
Accordingly, the functional limitations are only utilized in the claims as a vague attempt to capture unknown and undisclosed structures, sufficient to achieve some functional 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, from among the millions of structures possible, do or do not satisfy the functional limitations at issue.
Accordingly, the basic question of “what sequences do or do not satisfy the ‘wherein; clauses of claims 1 and 43, and satisfy all structural limitations of claims 1 and 43?” is left unanswered and unanswerable in view of the originally filed disclosure. The prior art does not specifically address these shortcomings.
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, and polypeptide biophysics. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of additional and exemplification what exact polypeptide structures, from among the vast genus potentially claimed, do or do not constitute affinity ligands that satisfy the functional limitations recited at amended claims 1 and newly added claim 43. Therefore, in the absence of sufficient structure/function teachings commensurate in scope with the instant claims, identifying particular compounds capable of affinity ligands, as required to practice the full scope of the claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
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 guidance permitting an artisan to distinguish structures that are included or excluded by the functional limitations commensurate in scope with the instant claims This also means that it is prima facie unclear what structures are 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 1-3 and 43 are rejected.
Response to Arguments
Applicant’s arguments with respect to claims 1-4 have been considered but are moot because claim 4 was canceled and the new grounds of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
At pages 5-6 of the Reply filed 7/21/2026, Applicant addresses the prior rejection under 35 USC 112(a), for written description. To the extent that the argument set forth at the first paragraph of page 6 of the Reply may apply to the new rejections, it is noted that Applicant only provides a conclusory statement alleging that the “wherein” clauses were “structural language” (see, e.g., Reply filed 7/21/2026 at 6 at 1st ¶), but fails to provide supporting citations or explanations for how such statements are “structural” limitations corresponding to a specific structure. To the contrary, as discussed in the new rejections, the “wherein” clauses are functional limitations that presumably impact disulfide bond placement and formation, which impact the pH, temperature, peptide concentration, etc. of the compositions in an unknown and unspecified manner, and such language does not correspond to a structure/function relationship of record. Accordingly, such amendments are not “structural” per se, because the amendments do not clearly and unambiguously limit the pending claim scope to particular, unambiguous structure or structures.
Accordingly, the amended claims 1-3 and newly added claims 41 and 43 are rejected as set forth above.
Allowable Subject Matter
Claim 40 is allowed.
Applicant may place the application in form for allowance, after-final, by canceling all claims other than claim 40.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US619792716 teaches and discloses variants of Protein A, including SEQ ID NO: 35 (i.e., AVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC).
US2019/0167576A117 (Jun. 6, 2019) was discussed in the previous action and remains pertinent to the claimed invention.
US6,013,76318 (Jan. 11, 2000) was discussed in the previous action, and remains pertinent to the claimed invention.
Conclusion
Claim 40 is allowed. Claims 1-3, 41, and 43 are rejected. Claim 42 is withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Cited in previous action
2 Cited in previous action
3 see MPEP § 2173.05(b)(II), discussing how references to variable objects may render a claim indefinite.
4 However, such embodiments raise antecedent basis issues with respect to the phrase “the two cysteine residues” as recited by claims 1 and 43.
5 If the leading Phe residue is deleted, for example, it results in Subunit-2 lacking a Cys residue at position 5 or position 34, as the remaining Cys residues would be at position 4 and position 33.
6 If the Cys at position 5 is deleted, it results in a Subunit-2 sharing 97.06% identity with SEQ ID NO: 18, but lacking a Cys residue at position 5 or position 34, as the remaining Cys would be at position 33.
7 Cited in previous action.
8 Cited in previous action.
9 Góngora-Benítez et al., Multifaceted roles of disulfide bonds. Peptides as therapeutics. Chem Rev. 2014 Jan 22;114(2):901-26. doi: 10.1021/cr400031z. Epub 2013 Oct 29. PMID: 24446748; hereafter “Gongora”.
10 Arolas et al., Folding of small disulfide-rich proteins: clarifying the puzzle. Trends Biochem Sci. 2006 May;31(5):292-301. doi: 10.1016/j.tibs.2006.03.005. Epub 2006 Apr 5. PMID: 16600598
11 Góngora-Benítez et al., Multifaceted roles of disulfide bonds. Peptides as therapeutics. Chem Rev. 2014 Jan 22;114(2):901-26. doi: 10.1021/cr400031z. Epub 2013 Oct 29. PMID: 24446748; hereafter “Gongora”.
12 See, e.g., Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2130 (2014), discussing an improper “zone of uncertainty” that fails to inform “with reasonable certainty” those of skill in the art the metes and bounds of the instant invention.
13 Góngora-Benítez et al., Multifaceted roles of disulfide bonds. Peptides as therapeutics. Chem Rev. 2014 Jan 22;114(2):901-26. doi: 10.1021/cr400031z. Epub 2013 Oct 29. PMID: 24446748; hereafter “Gongora”.
14 Arolas et al., Folding of small disulfide-rich proteins: clarifying the puzzle. Trends Biochem Sci. 2006 May;31(5):292-301. doi: 10.1016/j.tibs.2006.03.005. Epub 2006 Apr 5. PMID: 16600598
15 Góngora-Benítez et al., Multifaceted roles of disulfide bonds. Peptides as therapeutics. Chem Rev. 2014 Jan 22;114(2):901-26. doi: 10.1021/cr400031z. Epub 2013 Oct 29. PMID: 24446748; hereafter “Gongora”.
16 Cited in previous action.
17 Cited in previous action.
18 Cited in previous action.
Prosecution Insights