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 .
Claims Status
All previously presented Claims are cancelled. Claims 34-47 are newly added and are examined on the merits.
OBJECTIONS WITHDRAWN
Specification
Objections to the specification over hyperlinks and trademarks are withdraw in view of Applicant’s amended specification.
NEW OBJECTIONS
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o).
The Claims as amended reference new language, phrases, and limitations absent from the specification, including:
A peptide consisting of “a contiguous amino acid sequence” having a % identity “over the entirety of the amino acid sequence of the peptide”
The phrase “wherein the amino acid sequence includes at least both residues 559 and 580 of SEQ ID NO: 9”
Specific mention of residues 554, 556, 558, and 581 of SEQ ID NO: 9
Any mention of particular residues that are “not S” or “not T” or not “a conservative amino acid substitution thereof”
The entirety of the phrase “when residues 554, 559, 558, and 581 are present and residues 554 and 558 are S, residues 556 and 581 are not both alanine substituted”
SEQ ID NO: 9 wherein “The only substitutions” are at residues 554, 556, 558, and 581
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located at pp81-87, ¶000767, pp191-192, and ¶000859-000862.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Objections
Claim 34 is objected to because of the following informalities:
Claim 34 is objected to for reciting “...residues 554 and 558 and are S” (emphasis added), which does not make grammatical sense.
Appropriate correction is required.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
Claim Rejections - 35 USC § 112
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 34-47 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.
Claims 34 and 35 recite “an amino acid sequence at least 90% identical to contiguous amino acid sequence of human ALCAM as set forth in SEQ ID NO: 9 over the entirety of the amino acid sequence of the peptide” wherein the N-terminus and/or C-terminus corresponds to residue 559 or 580 of SEQ ID NO: 6. However, SEQ ID NO: 6 – only 23 residues in length – does not contain a “residue 559” or “residue 580”, and it is unclear to which residues the claims are referring.
In addition, it is unclear what is meant for the claimed peptide to have “an amino acid sequence at least 80% identical” or “an amino acid sequence at least 90% identical” to “a contiguous amino acid sequence of human ALCAM as set forth in SEQ ID NO: 9 over the entirety of the amino acid sequence of the peptide” as recited in both Claims 34 and 35. The recited phrase has no antecedent basis in the specification (see above objection), and it is unclear if the claims require % identity over the entire length of SEQ ID NO: 9 or if the peptide need only match a portion thereof. For example, SEQ ID NO: 6 as recited in Claim 34 (ii)(B) and several dependent claims is a 23aa peptide containing a truncated ALCAM sequence wherein residues 2-23 are the same as residues 559-580 of SEQ ID NO: 9, and therefore could not possibly be “at least 90% identical” to SEQ ID NO: 9.
Each of Claims 36-47, which depend from Claims 34 or 35, are rejected for the same reasons.
Claim 36 is drawn to the “peptide of claim 34 (i)”. However, a claim cannot depend from only a part of a previous claim. It is unclear as to whether Claim 36 is intended to encompass the additional limitations set forth in the remainder of Claim 34 or if instead the claim is meant to be an independent claim encompassing only the limitations set forth in item “i” of Claim 34.
Moreover, item “i” of Claim 34 recites “Z1 is absent or Z1 is selected from at least one of a proteinaceous moiety comprising from about 1 to about 50 amino acid residues”, and therefore residues 554, 556, 558, and 581 “of claim 34 (i)” as recited in Claim 36 lack antecedent basis.
Similarly, Claims 40-42 recite “the isolated or purified peptide of claim 34 (ii)”. It is unclear as to whether claims 40-42 are intended to encompass the additional limitations set forth in the remainder of Claim 34 or if instead the claims are meant to be independent claims encompassing only the limitations set forth in item “ii” of Claim 34.
Claim 37 depends from Claim 35 and recites “wherein the conservative amino acid substitution is a negatively charged amino acid”. However, there is ambiguity regarding what the limitation “the conservative amino acid substitution” refers to, as Claim 35 recites several instances of “a conservative amino acid substitution” in each of items (a)-(d).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 37 and 40-41 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 37 depends from Claim 35 and requires “the conservative amino acid substitution is a negatively charged amino acid”. However, each instance of “a conservative amino acid substitution” of Claim 35 refers to a substitution of either S or T (serine or threonine). However, the only “conservative” substitutions of S and T as defined by the instant specification are T and S, respectively, and neither S nor T are negatively charged (see, for example, ¶00404 and ¶000884 of the instant specification). Accordingly, negatively charged residues would not appear to satisfy the requirement of a “conservative amino acid substitution” for either serine or threonine, and Claim 37 therefore fails to incorporate all of the limitations of Claim 35.
Claims 40 and 41 require that the “peptide of claim 34 (ii)” is identical to SEQ ID NO: 9 or SEQ ID NO: 1, respectively. However, the peptide of Claim 34 ii requires that if residues 554, 556, 558, or 581 are present, they are “not S” or “not T”. SEQ ID NO: 9 and SEQ ID NO: 1, however, contain the recited residues (S or T) at each of the recited locations (SEQ ID NO: 9) or equivalent relative locations (SEQ ID NO: 1), and therefore fail to incorporate all of the limitations of Claim 34.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 34-47 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 claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
The Claims as amended include new phrases, terminology, limitations, and negative limitations absent from the original disclosure and which change the scope of the claims relative to that supported by the original disclosure. Examples of new matter in the claims include:
A peptide consisting of “a contiguous amino acid sequence” having a % identity “over the entirety of the amino acid sequence of the peptide”
The phrase “wherein the amino acid sequence includes at least both residues 559 and 580 of SEQ ID NO: 9”
Specific mention of residues 554, 556, 558, and 581 of SEQ ID NO: 9
Any mention of particular residues that are “not S” or “not T” or not “a conservative amino acid substitution thereof”
The entirety of the phrase “when residues 554, 559, 558, and 581 are present and residues 554 and 558 are S, residues 556 and 581 are not both alanine substituted”
SEQ ID NO: 9 wherein “The only substitutions” are at residues 554, 556, 558, and 581
In each of the above cases, the claims are drawn to subgenera and species not specifically described by the claims or specification as originally filed. “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”. See § MPEP 2163.05.
Claims 34-37, 39, 42, 44-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Summary
Each of Claims 34-37, 39, 42, 44-46 require a peptide with the function of inhibiting or modulating ligand-independent RAGE activation. However, the claims are drawn to peptides having 80% or 90% identity to recited sequences and thus encompass an extremely large number of potential species defined only by the required function and partial structure. The disclosure fails to provide a sufficient number of representative species or establish a structure-function relationship such that one of ordinary skill in the art could envisage a peptide modulator of RAGE commensurate in scope with the claims.
Scope of the claimed genus
The claims are drawn to a large number of potential species of RAGE inhibitor/modulator define by partial structure of 80% or 90% sequence identity to SEQ ID NO: 9, SEQ ID NO: 1, and/or SEQ ID NO: 6. Without any particular limits to which positions within the claimed peptides contain the 10-20% variation, the claims are drawn to an extraordinarily large number of possible species containing a multitude of mutations, substitutions, deletions, and insertions.
State of the relevant art
Both ALCAM and RAGE are well known to signal through NFκB in response to extracellular ligands such as S100 (See, for example: von Bauer et al. 2013. The Journal of Immunology, 191(1), 369-377.; IDS). In addition, modifications to the C-terminal tail of ALCAM have been shown to disrupt its association with intracellular components (Riet et al. 2014. Journal of cell science, 127(7), 1595-1606.; of record)
However, transactivation of an IgSF CAM by an activated GPCR is largely unexplored in the art and was first reported by Pickering et al. 2019 (The Journal of clinical investigation, 129(1), 406-421.; of record), which teaches that activation of AT1R by its ligand Ang II induces NFκB activity in the presence of RAGE (Fig. 3B). Pickering further teaches that selectively truncated or mutated RAGE peptides can block this transactivation (Fig. 6A). However, Pickering 2019 was published after the effective filing date of the instant application and does not constitute part of the prior art.
Description of representative species in the specification
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The disclosure provides examples of 3 “modulators”, “ALCAM559-580”, “RAGE370-390”, and “S391A-RAGE362-404”, and demonstrates their capacity to interfere with transactivation of ALCAM, RAGE, BCAM, MCAM, EpCAM, or CADM4 in response to stimulation of the GPCR angiotensin II receptor type 1 (AT1R) by its cognate ligand, angiotensin II (Fig. 2-7). However, only one of these species belongs to the claimed genus (ALCAM559-580). Given the large breadth of the claims, one of ordinary skill in the art would not reasonably consider the disclosure of but a single species of the claimed genus.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed activity.
The three disclosed modulators are each truncated/mutant variants of the cytosolic domain of ALCAM or RAGE and lack the ability to support transactivation of NFκB in the presence of stimulated AT1R (¶774; Fig. 3A; Fig. 5A). In contrast, the full-length cytosolic tails of ALCAM, RAGE, BCAM, MCAM, EpCAM, or CADM4 each respond similarly to full-length wild type counterparts in the same assay, resulting in p65-NFκB transcriptional output (¶761-763; Fig. 1F-G).
The disclosure proffers the hypothesis that the serine and threonine residues within the cytosolic tail of ALCAM may play “a structural role in facilitating signaling” upstream of NFκB, and these residues were specifically omitted in the creation of the ALCAM559-580 fragment (¶773). However, no mutations beyond the single truncated species that may test this hypothesis are disclosed, and no further investigation of the structure/function relationship between this sequence and its activity are disclosed. Further, the specification does not provide any functional characterization of the remaining residues within the ALCAM559-580 fragment to determine which of those is responsible and/or required for the observed behaviors (i.e. which peptides comprising only 80% sequence identity are expected to function the same in the disclosed assays?).
In addition, although BCAM, MCAM, EpCAM, or CADM4 cytosolic domains are sufficient for AT1R/NFκB transactivation, no variants thereof are disclosed that can modulate this activity (i.e. increase or decrease signaling when combined with a system in which this signaling already occurs – as is the case with ALCAM559-580, RAGE370-390, and S391A-RAGE362-404). Moreover, as the instant specification points out, the cytosolic domains of these IgSF CAMs “share limited sequence homology” – and it would be unclear what modifications can be made to said cytosolic tails to recapitulate the behavior observed for ALCAM559-580, RAGE370-390, and S391A-RAGE362-404.
Given the considerable breadth of the claims, minimal number of representative species, and a lack of guidance on the structural requirements of a “modulator” to meet the claimed function, one of ordinary skill in the art would be unable to envisage a peptide modulator of RAGE signaling commensurate in scope with the claims.
Claims 34-42 and 44-47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a peptide that inhibits RAGE ligand-independent activation of RAGE consisting of truncated ALCAM tail according to SEQ ID NO: 6 (ALCAM559-580), does not reasonably provide enablement for peptides longer than SEQ ID NO: 6 or having any additional residues from ALCAM. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The claims are drawn to a large genus of peptides containing at their core residues 559-580 of ALCAM, but allowing for considerable variation in said sequence (80% identity) as well as an unlimited number of possible flanking sequences (“Z1” or “Z2” comprising up to about 50 amino acids each). Because the claimed “modulator” function appears to be highly specific to the particular ALCAM559-580 truncation reduced to practice, the disclosure fails to provide adequate enablement for the full breadth of the claims.
For example, the each of ALCAM551-583 (full cytosolic tail) and the shorter truncation ALCAM559-580 are tested in the same assay to determine whether transactivation of NFκB transcriptional output occurs in response to AgII stimulation of AT1R. ¶774 of the specification states that ALCAM559-580 failed to increase expression of p65 following activation of AT1R by its ligand Ang II “unlike the full cytoplasmic domain of ALCAM, specifically ALCAM551-583”. Example 3 goes on to show that ALCAM559-580 is sufficient to disrupt both ALCAM551-583 and full-length ALCAM-mediated transactivation (Fig. 3G). Therefore, despite a high degree of identity between ALCAM559-580 and the slightly longer ALCAM551-583 (ALCAM559-580 is 10 residues shorter and comprises 100% identity over 70% of the length ALCAM551-583) their functional outputs according to the disclosed assay are entirely different.
Although the instant disclosure speculates that the difference may be owed to the lack of serine and threonine residues in the ALCAM559-580 truncation (¶773), no additional mutations or truncations of the ALCAM C-terminal domain are tested and the criticality of the serine and threonine residues to the observed behavior is not established. Accordingly, it remains unknown if or in which combinations mutating any or all of these S/T residues may result in a peptide having the claimed function. Further, given the similar size and high degree of structural similarity between ALCAM559-580 and the full cytoplasmic tail of ALCAM – yet disparate outputs in the disclosed assay – it is unclear which, if any, additional residues could be included or modified relative to ALCAM559-580 while preserving the claimed activity.
Given the lack of guidance and limited scope of the disclosure, including but a single working example, the skilled artisan would be faced with an undue amount of experimentation to uncover the full breadth of the claimed genus of modulators/inhibitors – including, for example, systematic truncations, mutagenesis, and combinations thereof, followed by characterization according to the disclosed assays – with a minimal expectation of success.
Response to Arguments
Applicant's arguments filed 11/13/2025 have been fully considered but they are not persuasive.
Applicant argues that the new claims “define the minimum structural features necessary to recapitulate the behaviour observed for ALCAM559-580 , i.e., an ALCAM peptide fragment with disruption to one or more serine or threonine residues in the cytosolic tail”.
As evidence, Applicant cites ¶0774 of the specification which reads in part: “The cytoplasmic domain of human ALCAM contains two serines and two threonines. ...[T]he inventors believe these residues to play a structural role in facilitating signaling mediated by the cytoplasmic tail leading to the induction of NFKB.”
However, such a hypothesis remains conjecture in the absence of experimental evidence, and, as stated above, the specification provides little to no support for peptides having the claimed activity beyond ALCAM559-580. No point mutations of these serine/threonine alone or in any combination were made, and, although ALCAM559-580 does indeed lack the serine/threonine residues of the ALCAM cytoplasmic domain, it lacks additional flanking residues with unknown structural or functional contributions to normal ALCAM behavior or the RAGE inhibitory activity of the selective truncation. Moreover, there is no evidence as to which of the remaining ALCAM559-580 residues are necessary or responsible for the observed activity.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 34-35 and 39 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Riet 2014 (Journal of cell science, 127(7), 1595-1606.; of record), herein “Riet”.
Riet teaches modified C-terminal ALCAM tails, including a tail wherein the threonine residues were mutated to alanine at positions 556 and 581 relative to full length ALCAM (Fig. 1A; ALCAM-ΔThr, “KKSKAASKHVNKDLGNMEENKKLEENNHKAEA”; alignment to instant SEQ ID NO: 9 below). Riet teaches that said mutations disrupt the ability for the ALCAM tail to interact with syntenin-1 – and thus the actin cytoskeleton (Pg. 1604, ¶1; Fig. 1B).
SEQ ID NO: 9 552 KKSKTASKHVNKDLGNMEENKKLEENNHKTEA 583
|||| |||||||||||||||||||||||| ||
ALCAM-ΔThr 1 KKSKAASKHVNKDLGNMEENKKLEENNHKAEA 32
Further, regarding Claim 39, ALCAM- ΔThr is 91.2% identical to instant SEQ ID NO: 1 (alignment below):
SEQ ID NO: 1 2 KKSKTASKHVNKDLGNMEENKKLEENNHKTEA 33
|||| |||||||||||||||||||||||| ||
ALCAM-ΔThr 1 KKSKAASKHVNKDLGNMEENKKLEENNHKAEA 32
Riet is silent on whether said mutant ALCAM modulates or inhibits RAGE ligand-independent activation of RAGE. However, such activity would be inherent to the mutant ALCAM tail of Riet.
Response to Arguments
Applicant's arguments filed 11/13/2025 have been fully considered but they are not persuasive.
Applicant argues that the sequence disclosed by Riet is “excluded from the scope of the new claims”. While the new limitations of Claim 34 (ii)(A)(e) or Claim 35 (i)(e) appear to be designed to exclude the teachings of Riet by specifying that the residues “are not alanine substituted”, the limitation is presented in the alternative (“or”) and thus Riet satisfies at least the species recited in items (b) and (d), wherein residue 556 or 581 is “not T”.
Moreover, Claim 34 as structured allows for a formula “Z1-M-Z2” wherein Z1 or Z2 comprise “a proteinaceous moiety comprising from about 1 to about 50 amino acid residues” without limit. As such, the peptide of Riet can also be interpreted under, for example, Claim 34 ii(B) as comprising a peptide “M” having an N and C terminus according to ALCAM amino acids 559 and 580 and further comprising a “Z1” and “Z2” element as follows:
ALCAM-ΔThr 1 KKSKAASKHVNKDLGNMEENKKLEENNHKAEA 32
“Z1” “M” “Z2”
Further, regarding Applicant’s argument that Riet “does not describe nor suggest which ALCAM residues are required to inhibit RAGE ligand-independent signalling”, the structure of the peptide taught by Riet meets the limitation of the instant claims, and such a property would be considered inherent to the said structure. Applicant is reminded that “something which is old does not become patentable upon the discovery of a new property” (see MPEP 2112(I)).
Conclusion
No claim is allowed.
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 BRYAN WILLIAM HECK whose telephone number is (703)756-4701. The examiner can normally be reached Mon-Fri 8:00am - 5:30pm.
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/BRYAN WILLIAM HECK/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643