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 .
The Examiner and Applicant’s representative discussed the possible Allowance of the instant claim 46, that was agreed upon by SPE Mike Hartley, during a telephone call. The Allowance was not accepted by the Applicant’s representative at that time but stated that they would discuss this with their Applicant.
The follow up phone calls to Applicant’s representative to discuss and/ or accept the allowance of the instant claim 46 that required cancelation of the claims 14,15,18,19,21-28,43,44 and 48 and the filing of terminal disclaimers over copending Application No. 16/365,166, U.S. Patent No. 9,415,122B2, U.S. Patent No. 8,686,112B2 and U.S. Patent No. 10,238,757B2 were not returned.
In view of the appeal brief filed on 11/20/25, PROSECUTION IS HEREBY REOPENED. A new ground of rejection is set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Claims Status
Claims 14,15,18,19,21-28,43,44,46 and 48 are pending in the application. Claims 14,15,18,19 and 21-28 are withdrawn from consideration.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
New Grounds of Rejection
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.
Claim(s) 43,44,46 and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Prantner et al. (Mol. Imag. 2003, 2, 333-341) in view of Brady-Kalnay (WO 2010/019884A1).
Prantner et al. (Mol. Imag. 2003, 2, 333-341) discloses Gd-DOTA-ᴅ-Tat peptide used for MR imaging (abstract; p336, MR spectroscopy and MR Imaging).
The Gd-DOTA-ᴅ-Tat comprises the structure
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(Figure 1) wherein the TAT targeting functionality provides cell targeting for specificity/selectivity and concentration of the contrast agent in the cell of interest and enhances both the relaxivity and ease of detection (p340, left column).
The DOTA chelator encompasses the DOTA chelator of the instant claims.
The Gd metal encompasses the chelated paramagnetic metal ion Gd of the instant claims.
The lysine linker (k) encompasses the lysine linker of the instant claims.
The lysine linker is bound to the DOTA chelator and comprises a free primary amine
moiety (Figure 1; p340, left column, first full paragraph) that encompasses the free amine moiety of the structure of the instant claims 46 and 48.
The lysine is covalently bound to the TAT peptide at an N-terminal glycine moiety via an amide bond of the instant claim 48.
The lysine covalently joins the N-terminal glycine moiety of the TAT peptide to a carboxyl group of the chelator of the instant claim 44.
Prantner et al. does not disclose the polypeptide SEQ ID NO: 5.
Prantner et al. further discloses that various target sequences can be envisioned that can bind to an intracellular protein of interest, etc. (p340, left column, first full paragraph).
Brady-Kalnay (WO 2010/019884A1) discloses a molecular probe comprising the target moieties SBK2 (SEQ ID NO: 5), etc. (p2, [0003],[0006]; p3, [0011]; p4, [0014-0015]; p13, [0036]; p26, [0076]; claim 9) for use in detection of cancer cells expressing an immunoglobulin (Ig) superfamily cell adhesion molecule (abstract; p2, [0003]).
The molecular probe comprises a single detectable moiety which can be detected by MRI, PET,
fluorescent imaging, etc. (e.g. radionuclide, fluorescent dyes, etc.) (abstract; p2, [0007]; p3, [0012]; p9,
[0024]; p12, [0032-0033]; p17, [0051-0052]; p18, [0053]; p20, [0060]; claims 1 and 10).
Examples of a single detectable agent bound to a peptides were described wherein the peptides SBK1 (SEQ ID NO:4), SBK2 (SEQ ID NO:5), SBK3 (SEQ ID NO:6), SBK4 (SEQ ID NO:7) are each coupled to Texas Red-X or Alexa-750 succinimidyl ester dye (p23, [0069]; p26, [0076]; p29, [0080]).
The detectable moiety comprises gadolinium, etc. (p18, [0056]).
The targeting agent SBK2 (SEQ ID NO: 5) encompasses the SEQ ID NO: 5 of the instant claims.
The detectable moiety may be directly or indirectly linked to the targeting agent (p2, [0007]; p3, [0012]; p17, [0051]).
Amino acid residues, such as lysine may be added to either terminus of the peptide for the purpose of providing a linker to conveniently affixed the peptide to the detectable moiety, etc. (p14, [0043]) that encompasses the lysine linking moiety of the instant claims.
The SBK2 labels Gli36[Symbol font/0x44]5 intracranial tumors in vivo and the probes are capable of crossing the
blood-brain barrier to label the intracranial GBM tumors (p5, [0021]; p19, [0057] p23, [0068]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the TAT peptide of Prantner et al. for the SEQ ID NO:5 of Brady-Kalnay for the advantage of site specific labeling of Gli36[Symbol font/0x44]5 intracranial tumors for in vivo MRI as the SEQ ID NO:5 is taught to cross the blood-brain barrier and Prantner et al. teaches that other target sequences are envisioned to bind to various targets of interest.
It would have been predictable to one of ordinary skill in the art to substitute one known targeting moiety with another known targeting moiety with a reasonable expectation of success to vary
the desired specific target site as Prantner et al. and Brady-Kalnay teach of binding the molecular probes
to various peptide targeting moieties via a lysine linker.
Maintained Rejections
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 43,44,46 and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42 and 62 of copending Application No. 16/365,166 in view of Prantner et al. (Mol. Imag. 2003, 2, 333-341) as stated in the office action mailed 5/28/25.
Claims 43,44,46 and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,5,6 and 11 of U.S. Patent No. 9,415,122B2 in view of Prantner et al. (Mol. Imag. 2003, 2, 333-341) as stated in the office action mailed 5/28/25.
Claims 43,44,46 and 48 are rejected on the ground of nonstatutory double patenting as
being unpatentable over claims 1,3,7 and 10 of U.S. Patent No. 10,238,757B2 in view of Prantner et al.
(Mol. Imag. 2003, 2, 333-341) as stated in the office action mailed 5/28/25.
Claims 43,44,46 and 48 are rejected on the ground of nonstatutory double patenting as being
unpatentable over claims 1,2,6-10,13,14 and 15 of U.S. Patent No. 8,686,112B2 in view of Prantner et al.
(Mol. Imag. 2003, 2, 333-341) as stated in the office action mailed 5/28/25.
Response to Arguments
Applicant's arguments filed 11/20/25 have been fully considered but they are not persuasive.
Applicant asserts that the claims of ‘166 application encompass a broad genus of possible detectable moieties and the office action has failed to provide any explanation for selecting a MRI contrast agent from the large number of possible detectable moieties, let alone a contrast agent having formula (I), i.e. a single dodecanetetraacetic acid (DOTA) chelating agent, wherein X is a chelated paramagnetic metal ion, L is an amino acid linker and Y is a polypeptide having the amino acid sequence of SEQ ID NO:5.
Also, Applicant asserts that Prantner et al. do not teach that the Gd-DOTA contrast agent could also be used as a targeted MRI contrast agent for extracellular targets as in the ‘166 application.
The ‘166 application was not used to teach of the specific DOTA chelating agent but was used to teach of a single SEQ ID NO:5 linked to a single detectable moiety.
The reference of Prantner et al. was not used to teach of targeting MRI contrast agents for extracellular targets but was used to teach of Gd-DOTA-ᴅ-Tat peptide MRI probe
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comprising a single DOTA chelator, a single Gd bound to a targeting peptide via a lysine linker.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the MRI detectable moiety of copending Application No. 16/365,166
for the DOTA chelator of Prantner to chelate a Gd metal for the advantage of enhanced relaxivity and ease of detection with a reasonable expectation of success, as Prantner et al. teaches of chelating a
single Gd to single DOTA-Lys-peptide for use in site specific targeting MRI imaging with enhanced relaxivity and ease of detection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the lysine linker covalently joins an N-terminal glycine of the peptide SEQ ID NO:5 to the carboxyl group of the MRI detectable moiety of copending Application No. 16/365,166 as Prantner et al. teaches of chelating a single Gd-DOTA to a single peptide via a lysine linker to yield an amide bond.
Applicant asserts that the claims of ‘122 patent recite a method of detecting cancer cells and encompass a broad genus of possible detectable moieties and the office action has failed to provide any explanation for selecting a MRI contrast agent from the large number of possible detectable moieties, let alone a contrast agent having formula (I), i.e. a single dodecanetetraacetic acid (DOTA) chelating agent, wherein X is a chelated paramagnetic metal ion, L is an amino acid linker and Y is a polypeptide having the amino acid sequence of SEQ ID NO:5.
Also, Applicant asserts that Prantner et al. do not teach that the Gd-DOTA contrast agent could also be used as a targeted MRI contrast agent for extracellular targets as in the ‘122 patent.
The ‘122 patent was not used to teach of the specific DOTA chelating agent but was used to teach of a single SEQ ID NO:5 linked to a single MRI detectable moiety for the method of detecting cancer cells and/or cancer cell metastasis, migration, dispersal and/or invasion.
The reference of Prantner et al. was not used to teach of targeting MRI contrast agents for extracellular targets but was used to teach of Gd-DOTA-ᴅ-Tat peptide MRI probe
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comprising a single DOTA chelator, a single Gd bound to a targeting peptide via a lysine linker.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the MRI detectable moiety of U.S. Patent No. 9,415,122B2 for the DOTA chelator of Prantner et al. to chelate a Gd metal for the advantage of enhanced relaxivity and ease of detection with a reasonable expectation of success, as Prantner et al. teaches of chelating a single Gd to single DOTA-Lys-peptide for use in site specific targeting MRI imaging with enhanced relaxivity and ease of detection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the lysine linker covalently joins an N-terminal glycine of the peptide SEQ ID NO:5 to the carboxyl group of the detectable moiety of U.S. Patent No. 9,415,122B2 as Prantner et al. teaches of chelating a single Gd-DOTA to a single peptide via a lysine linker to yield an amide bond.
Applicant asserts that claims of ‘757 patent encompass a broad genus of possible detectable moieties and the office action has failed to provide any explanation for selecting a MRI contrast agent from the large number of possible detectable moieties, let alone a contrast agent having formula (I), i.e. a single dodecanetetraacetic acid (DOTA) chelating agent, wherein X is a chelated paramagnetic metal ion, L is an amino acid linker and Y is a polypeptide having the amino acid sequence of SEQ ID NO:5.
Also, Applicant asserts that Prantner et al. do not teach that the Gd-DOTA contrast agent could also be used as a targeted MRI contrast agent for extracellular targets as in the ‘757 patent.
The ‘757 patent was not used to teach of the specific DOTA chelating agent but was used to teach of a single SEQ ID NO:5 linked to a single MRI detectable moiety used for the method of detecting cancer cells.
The reference of Prantner was not used to teach of targeting MRI contrast agents for extracellular targets but was used to teach of Gd-DOTA-ᴅ-Tat peptide MRI probe
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comprising a single DOTA chelator, a single Gd bound to a peptide via a lysine linker.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the MRI detectable moiety of U.S. Patent No. 10,238,757B2 for the DOTA chelator of Prantner et al. to chelate a Gd metal for the advantage of enhanced relaxivity and ease of detection with a reasonable expectation of success, as Prantner et al. teaches of chelating a single Gd to single DOTA-Lys-peptide for use in site specific targeting MRI imaging with enhanced relaxivity and ease of detection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the lysine linker covalently joins an N-terminal glycine of the peptide SEQ ID NO:5 to the carboxyl group of the detectable moiety of U.S. Patent No. 10,238,757B2 as Prantner et al. teaches of chelating a single Gd-DOTA to a single peptide via a lysine linker to yield an amide bond.
Applicant asserts that claims of ‘112 patent encompass a broad genus of possible detectable moieties and the office action has failed to provide any explanation for selecting a MRI contrast agent from the large number of possible detectable moieties, let alone a contrast agent having formula (I), i.e. a single dodecanetetraacetic acid (DOTA) chelating agent, wherein X is a chelated paramagnetic metal ion, L is an amino acid linker and Y is a polypeptide having the amino acid sequence of SEQ ID NO:5.
Also, Prantner et al. do not teach that the Gd-DOTA contrast agent could also be used as a targeted MRI contrast agent for extracellular targets as in the ‘112 patent.
The ‘112 application was not used to teach of the specific DOTA chelating agent but was used to teach of a molecular probe comprising a single SEQ ID NO:5 linked to with a single detectable moiety.
The reference of Prantner et al. was not used to teach of targeting MRI contrast agents for extracellular targets but was used to teach of Gd-DOTA-ᴅ-Tat peptide MRI probe
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comprising a single DOTA chelator, a single Gd bound to a peptide via a lysine linker.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to substitute the MRI detectable moiety of U.S. Patent No. 8,686,112B2 for the DOTA chelator of Prantner et al. to chelate a Gd metal for the advantage of enhanced relaxivity and ease of detection with a reasonable expectation of success, as Prantner et al. teaches of chelating a single Gd to single DOTA-Lys-peptide for use in site specific targeting MRI imaging with enhanced relaxivity and ease of detection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the lysine linker covalently joins an N-terminal glycine of the peptide SEQ ID NO:5 to the carboxyl group of the MRI detectable moiety of U.S. Patent No. 8,686,112B2 as Prantner et
al. teaches of chelating a single Gd-DOTA to a single peptide via a lysine linker to yield an amide bond.
Applicant asserts that they unexpectedly found that (i) a contrast agent having formula (I), i.e. a single dodecanetetraacetic acid (DOTA) chelating agent, wherein X is a chelated paramagnetic metal ion, L is an optional amino acid linker, and Y is a polypeptide having the amino acid sequence SEQ ID NO:5 has sufficient sensitivity, relaxivity and a clearance rate to detect glioma tumors in vivo by dynamic magnetic resonance imaging at concentrations not cytotoxic to subject compared to known glioma binding MRI contrast agents, such as SBK2-Tris-(Gd-DOTA)3 which do not have sufficient sensitivity to detect glioma tumors in vivo by dynamic MRI at concentrations that are not cytotoxic and (ii) such a contrast agent as claimed can readily cross the blood brain barrier for in vivo imaging of gliomas in the brain. These findings are in contrast to the teachings of the prior art that suggest larger contrast agents or contrast agents with more chelates would have greater relaxivity and increase MRI sensitivity in vivo.
The instant claims are not drawn to a method of MR imaging.
The ‘166 application, ‘122 patent, ‘757 patent and ‘112 patent teach of binding a single peptide of SEQ ID NO:5 to a single MRI detectable moiety and therefore, it would have been predictable to one of ordinary skilled in the art that the analogous SEQ ID NO:5 targeting peptide has the same properties and is capable of the same functions, such as crossing the BBB to target glioma tumors in vivo.
The Gd-DOTA-ᴅ-Tat peptide of Prantner et al.
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comprises a single DOTA chelator, a single Gd bound to a peptide via a lysine linker.
It would have been obvious to one of ordinary skill in the art to substitute the MRI detectable moieties for the DOTA of Prantner et al. to chelate a single Gd metal wherein the Gd-DOTA-SEQ ID NO:5 has the same properties and is capable of the same functions, such as the advantage of enhanced relaxivity and sufficient sensitivity in vivo by dynamic MRI at concentrations that are not cytotoxic.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618