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 .
Applicant's Response After Final Rejection, dated June 30, 2026, has been received. Upon further consideration the prosecution is REOPENED and Applicant's response has been entered. By way of this submission, Applicant has amended claim 23 and cancelled claim 22.
Claims 23 and 32-34 are pending in the application and under examination before the Office.
Response to Arguments
Applicant argues that clinical trials with the claimed method unexpectedly revealed that there was a specific and severe problem from co-administration of the peptide and the thrombolytic agent due to plasmin induced by the thrombolytic agent tissue plasminogen activator cleaving the peptide, and that this problem was not obvious until revealed by the clinical trial; for this reason, there was an unexpected benefit of using the D-amino acid substituted peptide over the original molecule.
Applicant's arguments have been considered fully but are not found to be persuasive.
Tissue plasminogen activator (tPA), which Applicant used as their thrombolytic agent, was known in the art to activate plasmin when administered for stroke. For example, Thiebaut (Lancet Neurol. 2018 Dec;17(12):1121-1132) teaches that plasminogen activators can promote fibrinolysis by converting plasminogen into active plasmin for the purpose of fibrinolytic cleavage of clots, in other words, the degradation of blood plasma proteins (see, e.g., abstract). For this reason, it would be expected that administration of tPA would increase peptide cleavage. Applicant's specification also states that thrombolytic agents work by promoting production of plasmin, which clears cross-linked fibrin mesh, making the clot soluble and subject to further proteolysis by other enzymes.
Additionally, Meyer (US20090281036A1, cited previously) teaches that TAT-based peptides are vulnerable to proteolytic degradation in serum (para. 0012). Meyer also teaches that the use of D-enantiomeric amino acids confers resistance to proteolytic degradation (para. 0016 and 0021).
It is also noted that U.S. patent 10,064,910, which Applicant relies upon as proof that the peptide and thrombolytic agent can be administered in combination without complication also teaches the use of D-amino acids (col. 11, lines 11-42), and that plasmin from administration of tPA may also cause proteolytic degradation (col. 21, lines 19-34).
The problem of degradation of TAT-based proteins and an appropriate solution was known in the art, and the addition of an agent that increases protein degradation would naturally exacerbate this problem. The application of a known solution to a known problem is prima facie obvious.
The rejection under 35 U.S.C. 103 over Tymianski is therefore maintained.
Applicant further argues that the double patenting rejections over U.S. patents 8,080,518, 8,940,699, 10,064,910, and 10,967,041 should also be withdrawn for the same reasons as provided above. This is not found persuasive, for reasons describes supra.
The double patenting rejections over U.S. patents 8,080,518, 8,940,699, 10,064,910, and 10,967,041 in view of Tymianski are therefore maintained.
The provisional double patenting rejections over applications 17/800,523 and 18/271,407 in view of Tymianski are therefore maintained.
Claim Rejections - 35 USC § 112
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.
Claim 32 is 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 32 recites a peptide with a sequence of ygrkkrrqrrrklsslESDV. This peptide is broader than what is claimed by parent claim 23, as the peptide ygrkkrrqrrrklsslESDV does not require an amino acid sequence comprising KLSSIESDV or KLSSIETDV. As such, claim 32 impermissibly broadens what is defined in its parent claim.
For the purpose of claim interpretation, this sequence is assumed to be ygrkkrrqrrrklssIESDV, which is consistent with Applicant's SEQ ID NO: 6.
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.
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.
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.
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.
Claims 23 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Tymianski (US20160228499A1).
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
While Tymianski does not teach the claimed subject matter in a single embodiment, it would be prima facie obvious to arrive at the claimed subject matter by following the teachings of Tymianski. Tymianski teaches the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV, which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV. Tymianski also teaches the use of D-amino acids, in particular a sequence of D-amino acids within the internalization peptide. Tymianski also teaches this peptide in the context of treatment for ischemic stroke. While Tymianski does not teach that cleavage of the active agent induced by the thrombolytic agent is reduced by the inclusion of the at least one D-amino acid, such a feature is a natural consequence of the inclusion of D-amino acids, and as such, must inherently be present within the peptide of Tymianski.
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 23 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7-9, and 11-13 of U.S. Patent No. 8,080,518 in view of Tymianski.
The '518 patent claims a method, comprising administering an internalization peptide comprising RKKRRQRRR, and a pharmacologic agent linked to the internalization peptide, comprising a peptide having an amino acid sequence comprising ESDV or ETDV (claim 1).
The '518 patent further claims the internalization peptide is a tat peptide having an amino acid sequence comprising YGRKKRRQRRR (claim 5).
The '518 patent further claims the pharmacologic agent is KLSSIESDV (claim 7).
The '518 patent further claims this method is useful for treating stroke (claim 11).
However, the '518 patent does not claim co-administration of a thrombolytic agent or D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '518 patent with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '518 patent were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '518 patent with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Claims 23 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 12 of U.S. Patent No. 8,940,699 in view of Tymianski.
The '699 patent claims a method of treating or inhibiting or delaying at least one sign or symptom of a condition mediated by excitotoxicity, comprising administering to a human subject a peptide having the amino acid sequence YGRKKRRQRRRKLSSIESDV (claim 1). According to the specification of the '699 patent, stroke is one such condition (col. 6, line 22).
However, the '699 patent does not claim co-administration of a thrombolytic agent or D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '699 patent with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '699 patent were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '699 patent with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Claims 23 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 11-16, and 23-27 of U.S. Patent No. 10,064,910 in view of Tymianski.
The '910 patent claims a method of treating a damaging effect of ischemia on the central nervous system, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy (claim 1).
The '910 patent further claims the ischemia may be cerebral ischemia (claim 5) or a stroke (claim 6).
The '910 patent further claims the PSD-95 inhibitor is the peptide tat-NR2B9c (claim 11-12).
The '910 patent further claims the reperfusion is performed by administering a thrombolytic agent such as tPA (claims 13-15).
The '910 patent further claims the interval between administering PSD-95 and reperfusion therapy is 30 minutes to 6 hours (claim 16).
However, the '910 patent does not claim a peptide with D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '910 patent with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '910 patent were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '910 patent with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Claims 23 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 8-12, and 22 of U.S. Patent No. 10,967,041 in view of Tymianski.
The '041 patent claims a method of treating a damaging effect of ischemia on the central nervous system, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (claim 1).
The '041 patent further claims the ischemia may be cerebral ischemia (claim 4) or a stroke (claim 5).
The '041 patent further claims the PSD-95 inhibitor is the peptide tat-NR2B9c (claim 8).
The '041 patent further claims the reperfusion is performed by administering a thrombolytic agent such as tPA (claims 9-11).
The '041 patent further claims the interval between administering PSD-95 and reperfusion therapy is 30 minutes to 6 hours (claim 12).
However, the '041 patent does not claim a peptide with D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '041 patent with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '041 patent were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '041 patent with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Claims 23 and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, and 44 of copending Application No. 17/800,523 in view of Tymianski.
The '523 application claims a method of treating ischemic stroke, comprising administering to the human subjects an active agent that inhibits PSD-95, cleavable by plasmin, and reperfusion, wherein the active agent that inhibits PSD-95 is administered at least 10 minutes before the tissue plasminogen activator, and wherein the active agent that inhibits PSD-95 is nerinetide (claim 1).
However, the '523 application does not claim co-administration of a thrombolytic agent or D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '523 application with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '523 application were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '523 application with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Claims 23 and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 62 of copending Application No. 18/271,407 in view of Tymianski.
The '407 application claims a method of treating a subject having or at risk of stroke, comprising administering the peptide YGRKKRRQRRRKLSSIESDV (claim 62).
However, the '407 application does not claim co-administration of a thrombolytic agent or D-amino acids.
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy on the subject (para. 0016).
Tymianski further teaches that such an agent may bind to an NDMAR2 subunit or NOS (para. 0018).
Tymianski further teaches that the reperfusion is performed by administering a thrombolytic agent such as tissue plasminogen factor (tPA) (para. 0086).
Tymianski further teaches that the subject may be human (para. 0020 and 0048).
Tymianski further teaches that the PSD-95 inhibitor is Tat-NR2B9c, which has the sequence YGRKKRRQRRRKLSSIESDV (para. 0010), which encompasses both the claimed internalization peptide of YGRKKRRQRRR, and the inhibitor peptide of KLSSIESDV.
Tymianski further teaches that the peptide can be modified by substitution of one or more of the amino acids in the natural L-isomeric form with amino acids in the D-isomeric form (para. 0065). Tymianski also teaches a variant of the above PSD-95 inhibitor comprising the amino acid sequence rrrqrrkkr, in which these amino acids are D-amino acids, linked to the peptide IETAV (para. 0067). Tymianski also teaches that the peptide IESDV is also effective in inhibiting binding of NMDAR2B to PSD-95 (para. 0067).
Tymianski further teaches that the PSD-95 inhibitor and reperfusion can be administered at the same time, or within 15 minutes of each other (para. 0103).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '407 application with teachings of Tymianski to arrive at the claimed invention. Peptides such as those claimed by the '407 application were known to be useful in treating stroke. Tymianski teaches combinations of this peptide and a thrombolytic agent, as well as modifications to the peptide to prevent proteolytic degradation. One of ordinary skill could combine the peptide of the '407 application with the thrombolytic agent and modifications of Tymianski to arrive at the claimed invention by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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