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 .
DETAILED ACTION
Response to Election/Restriction filed on October 17, 2025 and March 17, 2026 is acknowledged. Claims 1-13 are pending in the instant application.
Election/Restrictions
Applicant initially elected without traverse “List I” in the reply filed October 17, 2025. On March 17, 2025 the attorney further elected a homing peptide conjugate comprising a C-terminal CRKDK sequence, i.e. the fusion in instant claim 6.
The restriction is deemed proper and is made FINAL in this office action.
Claims 1-13 are examined on the merits of this office action.
Claim Rejections - 35 USC § 112, First Paragraph
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 1-5, 7-13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
The claims broadly recite a homing peptide guided decorin conjugate for use in treating epidermolysis bullosa, wherein the conjugate comprise a decorin segment and a homing peptide. The specification defines “decorin” broadly as referring to any isoform of a small leucine rich chondroitin sulfate proteoglycan, including human decorin isoforms A, B, C, or D, with or without N-terminal signal sequence and/or propeptide. The specification further states that “decorin” may comprise or consist of any one of SEQ ID Nos:6-20, and includes conservative sequence variants and peptidomimetics. Instant claim 4 claims “wherein the decorin segment comprises an amino acid sequence having at least 80% sequence identity to SEQ ID Nos:6-20, conservative variants thereof or peptidomimetic thereof. The specification defines “Decorin segment” (which is claimed) as part of the conjugate that comprise or consists of decorin (see paragraph 0032). Dependent claims further encompass decorin segments having broad sequence identity ranges, including variants retaining biological properties all of which fall within the specific definition by Applicant. Accordingly, the claims encompass a large genus including numerous decorin isoforms, fragments, truncations, variants, substituted sequences, peptidomimetics and conjugated forms.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. 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 specification appears to provide experimental data directed primarily to specific recombinant constructs identified as DCN-tCRK and comparisons to decorin alone. The disclosed working examples focus on particular constructs employing specific homing peptides and particular decorin forms. The specification does not demonstrate actual reduction to practice of the full claimed genus of decorin segments, isoforms, fragments, variants, and peptidomimetics now encompassed by the claims.
Accordingly, the disclosed examples do not constitute representative species of the claimed genus. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
Although Applicant provides a broad definitional statement for decorin and lists certain sequences, the specification does not set forth sufficient identifying characteristics to distinguish which among the many possible decorin fragments, altered sequences, peptidomimetics, or variants qualify as operable “decorin segments” within the claimed invention. The disclosure does not identify common structural features required for therapeutic activity in epidermolysis bullosa or for compatibility with the claimed conjugates across the full genus.
Physical/Chemical Properties
The specification generally describes decorin as a proteoglycan and references sequence identity ranges. However, no meaningful physical or chemical characteristics are provided that would allow one skilled in the art to recognize which modified fragments, truncated segments, substituted variants, or peptidomimetics within the broad claim scope would possess the required properties for use in the claimed conjugates.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification attributes certain biological properties to decorin, such as regulation of collagen fibril formation, prevention of tissue fibrosis, promotion of tissue regeneration, and antagonism of TGF-B. However, the specification does not disclose a sufficient correlation between specific structural features of the many claimed decorin isoforms, fragments, and variants and the asserted therapeutic functions in treating epidermolysis bullosa. Nor does the specification explain which portions of decorin are necessary or sufficient to retain such function when incorporated into the claimed conjugates.
Method of Making
While recombinant preparation of certain exemplary constructs may be described, the specification does not adequately describe how to make the full scope of claimed decorin segments, numerous sequence variants, peptidomimetics, and conjugates now encompassed by the claims. Broad references to routine methods does not substitute for written description of possession of the claimed subject matter.
Conclusion
The specification describes certain specific decorin conjugates, but does not reasonably convey possession of the full scope of the presently claimed genus encompassing any decorin isoform, fragment, segment, sequence variant, peptidomimetic, and related conjugate for treatment of epidermolysis bullosa. Therefore the claims lack adequate written description under 35 U.S.C. 112 (a).
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.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites that “the conjugate is a fusion protein or a peptidomimetic thereof”. The phrase “peptidomimetic thereof” is unclear and subject to multiple interpretations. Specifically, it is unclear whether “thereof” refers to a peptidomimetic of the fusion protein as a whole, only of the decorin segment, only the homing peptide, peptidomimetic of the conjugate generally or a structure merely mimicking certain functional properties. Additionally, peptidomimetic itself may encompass a broad range of compounds including modified peptides, non natural amino acid analogs, partially peptide based molecules, or non-peptide scaffolds, such that the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Jarvinen (US20090036349) as evidenced by Uniprot (protein accession PGS2_Human, see attached handout)
Claim interpretation: A homing peptide-guided decorin conjugate for use in the treatment of epidermolysis bullosa, wherein the conjugate comprises a decorin segment and a homing peptide, wherein the C-terminal end of the homing peptide consists of the amino acid sequence RKDK (SEQ ID NO: 1) or CRKDK (SEQ ID NO: 2). The claims are drawn to the conjugate decorin-homing peptide-RKDK or CRKDK. Given the consisting language regarding the homing peptide, the homing peptide has to terminate with RKDK or CRKDK and cannot have additional peptide/amino acid sequence following the RKDK. The phrase “for use” is interpreted as merely stating an intended use or purpose of an otherwise recited composition, absent structural limitations imparted by such language. Furthermore, regarding the term “decorin” and “decorin segment”, Applicants have defined “Decorin” as to be inclusive to variants of decorin, including as low as 80% sequence identity to SEQ ID Nos:6-20 and peptidomimetics thereof (paragraphs 0032-0033). Thus, given the broadest reasonable interpretation and the specific definition in the specification, “Decorin” and “Decorin segment” are inclusive to the variants and peptidomimetics thereof.
Jarvinen teaches compositions and methods useful for targeting regenerating tissue and wounds using peptides that selectively bind to and home to regenerating tissue and wound sites (see abstract, paragraph 0003-0005). Jarvinen further teaches peptide sequences identified from skin and tendon wounds including CRKDKC (SEQ ID NO:2), which selectively homes to skin wounds and tendon wounds (see paragraph 0171). Jarvinen teaches that these wound honing peptides can be used to deliver payloads to wound tissue with selectivity (paragraph 0027) and specifically teaches use of such peptides as a honing element for targeting delivery of decorin to the skin (see paragraph 0028). Jarvinen specifically teaches the fusion of Decorin-CRKDKC (see paragraph 0215, and also Figure 4A). Thus, Jarvinen teaches a decorin-honing peptide conjugate for use in treating wounds and skin injury.
Jarvinen does not expressly disclose that the c-terminal end of the homing peptide consists of RKDK or CRKDK as recited in the instant claims. However, Jarvinen teaches the closely related wound honing peptide CRKDKC, and further teaches that variants of the disclosed CAR and CRK peptide include substitutions and deletions of residues, including cysteine residues, and that deletions of cysteine or other labile residues may be desirable (see paragraph 0064-0066). Jarvinen also explains that the cysteine residues at both ends of CRKDKC are likely involved in cyclization through a disulfide bond (see paragraph 0171).
It would have been obvious before the effective filing date of the claimed invention to modify the CRKDKC peptide of Jarvinen by deleting on terminal cysteine residue to obtain CRKDK, or deleting both terminal cysteines/truncating to obtain RKDK, because Jarvinen expressly suggests residue deletions including cysteine deletions, and identifies the terminal cysteines as structural cyclization residues rather than the targeting core motif. Such optimization of known peptide sequences by terminal residue deletion would have been a routine matter yielding predictable variants while retaining would honing functionality.
Regarding the limitation of “for use in the treatment of epidermolysis bullosa” and “acquired epidermolysis bullosa” (claim 1, 13) and “for use in” throughout the claims, please note that it is regarded that "intended use" of a composition or product will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In Re Hack 114, USPQ 161. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitation. In the instant case, Jarvinen render obvious the identical conjugate of the instant claims including decorin and the c-terminal homing peptide and thus, the structure is capable of performing the intended use. The recitation “for use in the treatment of epidermolysis bullosa” does not positively recite any required step of administering the conjugate to a subject, dosage regiment, route of administration or otherwise active treatment limitation. Rather, the phrase merely describes an intended use for the claimed conjugate.
Regarding claim 2, Jarvinen teaches homing to skin and skin wounds (see paragraph 0028).
Regarding claim 3, Jarvinen teaches wherein the decorin segment is attached to the N-terminal end of the homing peptide (see paragraph 0215).
Regarding claim 5, Jarvinen teaches wherein the conjugate is a fusion protein (see paragraph 0215). As evidenced by Uniprot Protein Database (protein accession PGS2_Human, see attached handout) human decorin meets the limitations of at least 80% sequence identity to SEQ ID NO:6. Regarding claim 6, instant SEQ ID NO:21 is human decorin with GSEF linked to CRKDK. Jarvinen teaches GSEF linked to the CRK peptide in the fusion (see Figure 4). Thus, the combination of Jarvinen as evidenced by Uniprot teaches instant SEQ ID NO:21, human decorin-GSEF-CRKDK fusion.
Regarding claim 4, Jarvinen teaches wherein the decorin is human decorin (see Figure 4, paragraph 0215).
Regarding claims 7-10, Jarvinen teaches wherein the conjugate further comprises one or more additional moieties attached to the conjugate (see paragraph 0106); wherein the therapeutic is thrombolytics, beta blockers (see paragraph 0107) or steroid (paragraph 0108, which is an anti-inflammatory agent) or a peptide (see paragraph 0116).
Regarding claim 11, Jarvinen teaches wherein the conjugate comprises a detectable agent (see paragraph 0121). Regarding claim 12, Jarvinen teaches wherein the conjugate is in combination with a pharmaceutically acceptable carrier (see paragraph 0131).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
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