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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/16/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because the numbers on Figures 11-15 are blurred. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Formula I on page 17 of the specification is missing. It is advised that Applicant remove any references to Formula I from the specification.
Formula II is mislabeled as “Formula 2” on page 20, which is inconsistent with the prior use of “Formula I.” It is advised that Applicant use Roman numerals.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
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.
Claims 1-3, 5, 7-21, and 24 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.
Claim 1 recites a peptide hydrogel formed from an amphiphilic cationic ß-hairpin peptide, wherein the amphiphilic cationic ß-hairpin peptide comprises an unnatural lysine. The genus of peptide hydrogels formed from amphiphilic cationic ß-hairpin peptides is broad and includes any amino acid sequence of any length that can form the desired result of a ß-hairpin hydrogel. As such, there are many sequences of amino acids that can form peptide hydrogels in this manner, but Applicant as only disclosed eleven peptide sequences. These sequences are not a representative sample of the claimed genus of peptide hydrogels, as they are very similar sequences, most of which with the same length and many shared amino acids and motifs. Here, Applicant has not disclosed a representative sample of sequences to indicate that Applicant had possession of the claimed genus. Specifically, Applicant disclosed and has fulfilled the requirements of written description for the following sequences: VLTXVXTXVPPTXVQVXVFV (SEQ ID NO: 1), VXTXVEVEVPPTEVETXVXV (SEQ ID NO: 2), VETXVEVXVPPTEVXTEVXV (SEQ ID NO: 3), VXVXVXVXVPPTXVXVXVXV (SEQ ID NO: 4), VXVXVXVXVPPTXVEVXVXV (SEQ ID NO: 5), YGGASVXA (SEQ ID NO: 9), YGGASVGA (SEQ ID NO: 10), YGGASVXA (SEQ ID NO: 11), YGGASVKA (SEQ ID NO: 12), VXVXVXVXVPPTXVEVXVXV (SEQ ID NO: 13), VKVKVKVKVPPTKVEVKVKV (SEQ ID NO: 14), wherein X is the modified lysine of Formula 2. Here, all of the peptides have either a valine or tyrosine as the first amino acid, they all have valine or alanine as the last amino acid, and they are either 20 or 8 amino acids in length. Additionally, the following tripeptides and tetrapeptides are has fulfilled the requirements of written description for: XIA, XPA, FHXV, FSXV, FQXV, and FRXV. Here, all of the peptides have the unnatural lysine, X, or phenylalanine as the first amino acid, and, again, they all have Valine or Alanine as the final amino acid. As such, Applicanthas not fulfilled the requirements of written description for peptides that differ in length from the peptides described above (which have lengths of 3, 4, 8, and 20 amnio acids), Applicant has not fulfilled the requirements of written description for peptides that begin with amino acids that are not the unnatural lysine, X, phenylalanine, valine, or tyrosine, and Applicant has not fulfilled the requirements of written description for peptides that end with amino acids that are not alanine or valine. Moreover, Applicant has not fulfilled the requirements of written description for peptides that contain amino acids not listed in the aforementioned peptides. For example, Applicant does not disclose or demonstrate possession of any embodiments with tryptophan or methionine.
With regard to claim 2, as discussed above, Applicant does not fulfill the requirements of written description for peptides of lengths or compositions beyond the sequences discussed above. For example, Applicant has not fulfilled the requirements of written description for peptide hydrogels containing tryptophan or methionine, Applicant has not fulfilled the requirements for peptide hydrogels of 3, 4, 8, and 20 amino acids in length, and Applicant has not fulfilled the requirements for peptides beginning with amino acids outside of the unnatural lysine, tyrosine, phenylalanine, or valine or ending with amino acids outside of alanine or valine. Applicant has, however, fulfilled written description for the sequences discussed above.
With regard to claim 3, as discussed above, Applicant does not fulfill the requirements of written description for peptides of lengths or compositions beyond the sequences discussed above. For example, Applicant has not fulfilled the requirements of written description for peptides containing tryptophan or methionine, Applicant has not fulfilled the requirements for peptides of 3, 4, 8, and 20 amino acids in length, and Applicant has not fulfilled the requirements for peptides beginning with amino acids outside of the unnatural lysine, tyrosine, phenylalanine, or valine or ending with amino acids outside of alanine or valine. Applicant has, however, fulfilled written description for the hydrogels with the sequences discussed above.
With regard to claim 5, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide of claim 1. As such, Applicant has not fulfilled the requirements for the acylation or amidation of the peptide hydrogels of claim 1, as Applicant has not fulfilled the requirements for the peptide hydrogels themselves.
With regard to claim 7, the claim recites one or more unnatural lysine residues in an amphiphilic cationic ß-hairpin peptide are linked to a detectable marker. The term detectable marker is not defined in the specification or well-known or commonly understood in the prior art. As such, the genus of “detectable marker” is broad and encompasses any biological or chemical indicator that can be linked to the ß-hairpin peptide. Applicant does not, however, disclose a representative sample of detectable markers to convey that Applicant had possession of the genus of detectable markers. Specifically, Applicant discloses only detectable markers with triiodo groups. This does not convey that Applicant was in possession of the entire genus. Further, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels attached to a detectable marker.
With regard to claim 8, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels attached to a detectable marker contrast agent.
With regard to claim 9, the claim recites a peptide hydrogel contrast agent comprising a triiodo group. The claim includes the broad genus of any contrast agent with a triiodo group. Applicant has not, however, disclosed a representative sample of contrast agents with triiodo groups to reasonably portray that Applicant was in possession of a representative sample of species to claim the genus. Rather, Applicant disclosed six similar contrast agents comprising a triiodo group. This is not a representative sample to reasonably convey that Applicant was in possession of the species that constitute the claimed genus. Further, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels attached to a detectable marker contrast agent with a triiodo group.
With regard to claim 10, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels attached to a detectable marker contrast agent with a triiodo group.
With regard to claim 11, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels attached to a detectable marker contrast agent with a triiodo group.
With regard to claim 12, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels have properties of rheological recovery.
With regard to claim 13, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels have a storage modulus of greater than 40 Pascal in the absence of shear.
With regard to claim 14, the claim recites a peptide hydrogel comprising about 10 mM to about 400 mM NaCl and a pH of from about 7.0 to about 9.0. Applicant does not, however, disclose a representative sample of peptide hydrogels within this range of pH and NaCl content to reasonably convey that Applicant was in possession of the species that constitute the claimed genus. More specifically, the only embodiments taught in detail have pH 7.4 and 150 mM NaCl (see [0121]). Further, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels comprising specified amounts of NaCl or a specified pH.
With regard to claim 15, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels comprising a specified amount of NaCl or a specified pH.
With regard to claim 16, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for those peptide hydrogels comprising a specified w/v.
With regard to claim 17, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for their use in a syringe.
Claim 18 recites a method of making a peptide hydrogel comprising a contrast agent. The method is directed at making a peptide hydrogel formed from an amphiphilic cationic ß-hairpin peptide, wherein the amphiphilic cationic ß-hairpin peptide comprises an unnatural lysine. The genus of peptide hydrogels formed from amphiphilic cationic ß-hairpin peptides is broad and includes any amino acid sequence of any length that can form the desired result of a ß-hairpin hydrogel. As such, there are many sequences of amino acids that can form peptide hydrogels in this manner, but Applicant as only disclosed eleven peptide sequences. These sequences are not a representative sample of the claimed genus of peptide hydrogels, as they are very similar sequences, most of which with the same length and many shared amino acids and motifs. Here, Applicant has not disclosed a representative sample of sequences to indicate that Applicant had possession of the claimed genus. As such, applicant has not demonstrated possession of the claimed hydrogel. Further, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for the method of making those peptide hydrogels.
With regard to claim 19, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for the method of making those peptide hydrogels wherein the strained DIFO moiety is BCN or DBCO.
With regard to claim 20, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for the method of making those peptide hydrogels wherein the contrast agent for CECT imaging is linked to the strained DIFO moiety by a PEG linker.
With regard to claim 21, as discussed above, Applicant has not fulfilled the requirements of written description for the peptide hydrogels of claim 1 and, as such, necessarily has not fulfilled the requirements for the method using those peptide hydrogels in imaging a subject.
With regard to claim 24, the genus of polypeptides claimed in the language of claim 24 includes any polypeptide that contains the unnatural lysine linked by a peptide bond to the polypeptide, but Applicant as only disclosed eleven peptide sequences. These sequences are not a representative sample of the claimed genus of polypeptides, as they are very similar sequences, most of which with the same length and many shared amino acids and motifs. Here, Applicant has not disclosed a representative sample of sequences to indicate that Applicant had possession of the claimed genus. Specifically, Applicant disclosed and has fulfilled the requirements of written description for the following sequences: VLTXVXTXVPPTXVQVXVFV (SEQ ID NO: 1), VXTXVEVEVPPTEVETXVXV (SEQ ID NO: 2), VETXVEVXVPPTEVXTEVXV (SEQ ID NO: 3), VXVXVXVXVPPTXVXVXVXV (SEQ ID NO: 4), VXVXVXVXVPPTXVEVXVXV (SEQ ID NO: 5), YGGASVXA (SEQ ID NO: 9), YGGASVGA (SEQ ID NO: 10), YGGASVXA (SEQ ID NO: 11), YGGASVKA (SEQ ID NO: 12), VXVXVXVXVPPTXVEVXVXV (SEQ ID NO: 13), VKVKVKVKVPPTKVEVKVKV (SEQ ID NO: 14), wherein X is the modified lysine of Formula 2. Here, all of the peptides have either a valine or tyrosine as the first amino acid, they all have valine or alanine as the last amino acid, and they are either 20 or 8 amino acids in length. Additionally, the following tripeptides and tetrapeptides are has fulfilled the requirements of written description for: XIA, XPA, FHXV, FSXV, FQXV, and FRXV. Here, all of the peptides have the unnatural lysine, X, or phenylalanine as the first amino acid, and, again, they all have Valine or Alanine as the final amino acid. As such, Applicant is not has fulfilled the requirements of written description for peptides that differ in length from the peptides described above (which have lengths of 3, 4, 8, and 20 amnio acids), Applicant is not has fulfilled the requirements of written description for peptides that begin with amino acids that are not the unnatural lysine, X, phenylalanine, valine, or tyrosine, and Applicant is not has fulfilled the requirements of written description for peptides that end with amino acids that are not alanine or valine. Moreover, Applicant is not has fulfilled the requirements of written description for peptides that contain amino acids not listed in the aforementioned peptides. For example, Applicant does not disclose or demonstrate possession of any embodiments with tryptophan or methionine.
Claims 4 and 6 are not rejected under 35 U.S.C. 112(a) for failing to meet the requirements of written description on the grounds that Applicant has sufficiently demonstrated possession of the peptides of claims 4 and 6 by reciting the specific embodiments both in the claims and in the specification. Similarly, claims 22 and 23 are not rejected under 35 U.S.C. 112(a) for failing to fulfill the requirements of written description because Applicant has demonstrated possession the unnatural lysine residue.
Claim Rejections - 35 U.S.C. § 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 18, 22, and 23 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.
With regard to claim 18 recites the limitation "a method of making the peptide hydrogel.” There is insufficient antecedent basis for this limitation in the claim. It is not clear what the phrase “the peptide hydrogel” refers to in the context of the claim. As such, the subject matter which Applicant regards as the invention is not particularly pointed out and distinctly claimed.
Claim 22 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. Specifically, Formula I is missing from claim 22. It is advised that Applicant remove Formula I and references to Formula I.
Claim 23 recites the limitation that the unnatural lysine residue of claim 22, wherein, in Formula 1, X1 is Fmoc and X2 is Boc or Teoc. “Formula 1” is undefined in the disclosure, and there is insufficient antecedent basis for this limitation in the claim. It is advised that Applicant reference “Formula 2” or remove references to the formula.
Allowable Subject Matter
Claims 4 and 6 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claims 4 and 6 are not rejected because the claimed peptides contain novel sequences on account of the inclusion of the novel unnatural lysine of Formula 2. Given that both claims 4 contain sequences with the novel unnatural lysine, they contain allowable subject matter.
Summary
Claims 1-3, 5, 7-21, and 24 are rejected under 35 U.S.C. 112(a) for failing to meet the written description requirement. Claims 18, 22, and 23 are rejected under 35 U.S.C. 112(b) for failing to distinctly and particularly claim the subject matter that applicant regards as the invention. Claims 4 and 6 are objected to because they depend on at least one of the claims rejected above. No claim is allowed.
Conclusion
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/BRENDAN PATRICK NOONAN OLISS/Examiner, Art Unit 1658 /LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654