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
Election/Restrictions
Applicant’s election without traverse of Group I and SEQ ID NO: 114 (YGrKKRrQrRRkLSSIESDV) in the reply filed on 3/5/2026 is acknowledged.
Claims 57-58, 60 and 62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 3/5/2026.
Status of the Claims
Claims 1-15, 29, 56-58, 60 and 62 are pending in this application.
Claims 57-58, 60 and 62 are withdrawn from consideration as being drawn to a non-elected invention.
Claims 1-15, 29 and 56 are presently under consideration as being drawn to the elected species/invention.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 should be rewritten to recite “An active agent comprising an internalization peptide linked to an inhibitor peptide, wherein the active agent inhibits Postsynaptic density protein 95 (PSD-95) binding to nitric oxide synthase (NOS) and/or N-methyl D-aspartate receptor subtype 2B (NMDAR2B), wherein the internalization peptide has an amino acid sequence comprising RKKRRQRRR (SEQ ID NO:13) and the inhibitor peptide has a sequence comprising ESDV (SEQ ID NO:14) at the C-terminus, or a variant thereof with up to five substitutions or deletions total in the sequence of the internalization peptide and inhibitor peptide, wherein at least the four C-terminal amino acids of the inhibitor peptide are L-amino acids, and 3-5 residues of the internalization peptide are D-amino acids”. Appropriate correction is required.
Claim Rejections - 35 USC § 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.
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 1-15 and 56 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 claims are drawn to an active agent comprises an internalization peptide linked to an inhibitor peptide, which inhibits PSD-95 binding to NOS and/or NMDAR2B, wherein the internalization peptide has an amino acid sequence comprising RKKRRQRRR (SEQ ID NO:13) and the inhibitor peptide has a sequence comprising ESDV (SEQ ID NO:14) at the C-terminus, or a variant thereof with up to five substitutions or deletions total in the sequence of the internalization peptide and inhibitor peptide, wherein at least the four C-terminal amino acids of the inhibitor peptide are L-amino acids, and 3-5 residues of the internalization peptide are D- amino acids.
When referring to the variants of the internalization peptide and inhibitor peptide, the specification does not provide any structural attributes.
Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“A definition by function alone “does not suffice” to sufficiently describe a coding sequence because it is only an indication of what the gene does, rather than what it is”).”
Here, the specification fails to describe what part of the sequences correlate with the required activity (i.e. to be an internalization peptide; and to inhibit PSD-95 binding to NOS and/or NMDAR2B).
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad.
Based on the teachings of the specification, the variant of the internalization peptide can be any peptide comprising RKKRRQRRR, wherein up to five amino acids can be substituted or deleted.
Similarly, the variant of the inhibitor peptide can be any peptide comprising ESDV, wherein up to five amino acids (i.e. all of them) can be substituted or deleted.
However, the specification fails to provide a representative number of examples for the claimed variants of the internalization peptide and inhibitor peptide.
The specification does not provide any teaching of what modifications can be made within the claimed sequence to allow for the claimed function.
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 a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”).
Therefore, since the specification fails to identify any relevant structural characteristics that can be attributed to the claimed function and activity, the claimed invention lacks written description.
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 2 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 2 depends upon itself, thus it is indefinite. In order to advance prosecution, claim 2 has been interpreted as being dependent upon claim 1.
Claim Rejections - 35 USC § 103
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 1-15, 29 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Garman (WO 2015/181756).
With respect to claims 1 and 56, Garman teaches a chloride salt of a peptide which is TAT-NR2B9c (SEQ ID NO: 6) or differs from TAT-NR2B9c by up to 5 amino acid substitutions, insertions or deletions (claim 1).
It is noted that SEQ ID NO:6 corresponds to the sequence YGRKKRRQRRR-KLSSIESDV (para [0057]).
Garman also teaches that SEQ ID NO: 6 inhibits the interaction of PSD-95 with NMDAR2B (para [0075]).
Garman further teaches that the peptidomimetic may include 1, 2, 3, 4, 5, at least 50'%, or all D-amino acid residues (para [0048]).
Therefore, one of ordinary skill in the art would have arrived at the at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) and would have reasonably expected said sequence to inhibit the interaction of PSD-95 with NMDAR2B.
Furthermore, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham, including the exemplary rationales: (A) Combining prior art elements according to known methods to yield predictable results;
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(B) Simple substitution of one known element for another to obtain predictable results;
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(C) Use of known technique to improve similar devices (methods, or products) in the same way;
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(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
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(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
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(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP 2143).
One of ordinary skill in the art would have arrived at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) by applying any of the (A) to (G) rationales discussed above.
As discussed in the rejection under 35 U.S.C. 112(b) above, claim 2 has been interpreted as being dependent upon claim 1.
With respect to claims 2-15 and 29, as discussed above, one of ordinary skill in the art would have arrived at the elected species, thus reading on instant claims 2-15 and 29.
Claims 1-15 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Tymianski (US 2020/0222492) in view of Guichard et al. (Proc. Nati. Acad. Sci., Vol. 91, pp. 9765-9769, 1994) and Bonny (US 2012/0058137).
With respect to claim 1, Tymianski teaches a method which comprises administering an agent, wherein the agent is YGRKKRRQRRR-KLSSIESDV (claim 13).
Tymianski do not teach that 3-5 residues of the internalization peptide are D-amino acids.
Guichard et al. teach that “[T]he development of neuropeptides, peptide hormones, peptide antibiotics, or peptide-based synthetic vaccines is strongly impaired by the high susceptibility of peptides to proteolysis, which limits, inter alia, parental and oral administration. For many years intense work has been focused on the synthesis of peptide analogues in the search for mimics with enhanced activity and biological half-lives. Examples of modifications introduced in peptides are the replacement of L-amino acid residues by D-amino acids or by unnatural residues (e.g., sarcosine and 3-alanine) and the modification of peptide bonds. These changes provide pseudopeptides or peptidomimetics with a higher metabolic stability, since most natural proteases cannot cleave D-amino acid residues and nonpeptide bonds” (page 9765, left column, 2nd para).
Guichard et al. also teach that “[o]ne of the potential advantages of using peptide analogues containing D-amino acid residues or reversed peptide bonds rests in their much higher resistance to proteases, which could increase their immunogenicity compared to natural L-peptides” (page 9768, left column, 3rd para).
Similarly, Bonny teaches various transporter cargo conjugates comprising HIV TAT residues 49-57 (SEQ ID NO: 2), or a variant thereof (claim 1).
Bonny further exemplifies the variant rKKRrQRRr (paras [0492], [0513], [0518], [0525]; Table 1; passim).
It is noted that SEQ ID NO: 2 consists of the sequence RKKRRQRRR.
Bonny also teaches that “[t]he content of D-amino acids provides a further variety of useful properties. For example, such (poly-)peptides are more stable (especially in vivo) and show lower immunogenicity (para [0057]).
It would have been obvious to one of ordinary skill in the art at the time of the invention concerned with the treatment of neurological disorders to make an analog of YGRKKRRQRRR-KLSSIESDV comprising D-amino acids because peptide analogs comprising D-amino acids have much higher resistance to proteases, thereby increasing their immunogenicity compared to natural L-peptides.
Alternatively, the MPEP 2144.09 states that “[C]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.)”.
Therefore, one of ordinary skill in the art concerned with the treatment of neurological disorders would have arrived at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) and would have reasonably expected said sequence to have similar properties to the sequence of Tymianski (i.e. YGRKKRRQRRR-KLSSIESDV).
Furthermore, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham, including the exemplary rationales: (A) Combining prior art elements according to known methods to yield predictable results;
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(B) Simple substitution of one known element for another to obtain predictable results;
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(C) Use of known technique to improve similar devices (methods, or products) in the same way;
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(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
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(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
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(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP 2143).
One of ordinary skill in the art would have arrived at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) by applying any of the (A) to (G) rationales discussed above.
As discussed in the rejection under 35 U.S.C. 112(b) above, claim 2 has been interpreted as being dependent upon claim 1.
With respect to claims 2-15 and 29, as discussed above, one of ordinary skill in the art would have arrived at the elected species, thus reading on instant claims 2-15 and 29.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15, 29 and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. 10206973, or over claims 1-7 of U.S. Patent No. 10758589, or over claims 1-30 of U.S. Patent No. 11266714, or over claims 1-26 of U.S. Patent No. 11911438.
For the sake of brevity, the rejections over ‘973, ‘589, ‘714 and ‘438 will be discussed together.
With respect to claims to claims 1 and 56, ‘973, ‘589, ‘714 and ‘438 teach a chloride salt of a peptide which is TAT-NR2B9c (SEQ ID NO: 6) or differs from TAT-NR2B9c by up to 5 amino acid substitutions, insertions or deletions (claim 1).
It is noted that SEQ ID NO:6 corresponds to the sequence YGRKKRRQRRR-KLSSIESDV.
‘973, ‘589, ‘714 and ‘438 also teach that SEQ ID NO: 6 inhibits the interaction of PSD-95 with NMDAR2B (‘973 at column 7, lines 14-15; ‘589 at column 8, lines 18-19; ‘714 at column 8, lines 17-18; ‘438 at column 8, lines 17-18).
‘973, ‘589, ‘714 and ‘438 further teach that the peptidomimetic may include 1, 2, 3, 4, 5, at least 50'%, or all D-amino acid residues (‘973 at column 10, lines 23-25; ‘589 at column 10, lines 47-49; ‘714 at column 10, lines 29-31; ‘438 at column 10, lines 29-31).
Please note that it is proper to turn to and rely on the disclosure of a patent application to ascertain what constitutes an obvious modification. This position is supported by the courts. See In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
Therefore, one of ordinary skill in the art would have arrived at the at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) and would have reasonably expected said sequence to inhibit the interaction of PSD-95 with NMDAR2B.
Furthermore, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham, including the exemplary rationales: (A) Combining prior art elements according to known methods to yield predictable results;
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(B) Simple substitution of one known element for another to obtain predictable results;
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(C) Use of known technique to improve similar devices (methods, or products) in the same way;
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(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
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(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
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(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP 2143).
One of ordinary skill in the art would have arrived at the elected amino acid sequence (i.e. SEQ ID NO: 114, YGrKKRrQrRRkLSSIESDV) by applying any of the (A) to (G) rationales discussed above.
As discussed in the rejection under 35 U.S.C. 112(b) above, claim 2 has been interpreted as being dependent upon claim 1.
With respect to claims 2-15 and 29, as discussed above, one of ordinary skill in the art would have arrived at the elected species, thus reading on instant claims 2-15 and 29.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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, MELISSA FISHER can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
Prosecution Insights