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 .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/26/2025 has been entered.
Status of Claims
Claims 1-5 and 7-13 are pending. Claims 4-5 are withdrawn. Claims 12 and 13 are new. Claim 6 is canceled. Claims 1-3 and 7-13 are under examination.
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 1-3 and 7-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that, for a claimed genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The claims are directed to detecting a claimed protein by obtaining a sample; contacting the sample with a target peptide comprising a recognition sequence of SLYGSSRHTAPISF (SEQ ID NO. 2); and detecting binding between the targeting peptide and the at least one protein.
The claims as a whole cover a genus of samples with a single claimed protein that simply binds to the recognition of SLYGSSRHTAPISF for detection. Explicit in the claims is that such sequence and proteins possess certain functional characteristics; namely, each individual protein would have the ability to directly bind to the claimed sequence.
Level of skill and knowledge in the art:
Martinez et al. discloses the heterogeneous pathophysiology of traumatic brain injury (TBI) is a barrier to advancing diagnostics and therapeutics. Martinez teaches A2 sequence (see Table 1 and Table S4). Martinez also teaches that neurodegenerative pathways such as AD, PD, and ALS were only identified in SA1 group and not in the A2 group (see pg. 8, right col., para. 1). For the A2 targeting construct binds to a limited number of proteins (see Tables 2 and S4 (supplementary)). Martinez teaches identified targeting motifs based on the CDR 2 structure of dAbs for acute (1 day post-injury) and subacute (7 days post-injury) and immunoprecipitation-mass spectrometry indicated that the acute TBI targeting motif recognized targets associated with metabolic and mitochondrial dysfunction, whereas the subacute TBI motif was largely associated with neurodegenerative processes (see abstract). (“Uncovering temporospatial sensitive TBI targeting strategies via in vivo phage display”, Science Advances, vol., 8, eabo5047, published 2022).
The disclosure:
The specification only discloses proteins identified in the A2 (SLYGSSRHTAPISF) condition were highly expressed in the TCA cycle and pyruvate metabolism in comparison to other pathway analysis categories (see para. [0034], as filed 10/03/2023). The specification discloses IP-MS analysis identified 18-20 proteins specific to injury when using A2 and S1 as capture antibodies and pathway analysis of A2-specific proteins identified the TCA cycle and pyruvate metabolism pathway as highly represented processes and comparatively, proteins implicated in Parkinson’s disease and apoptosis signaling pathways were highly represented for SA1-specific proteins [0078].
In other words, the specification discloses a specific TBI sample containing acute stage to use A2 sequence for measurements through immunoprecipitation-mass spectrometry for protein detection. The instant application has not provided a sufficient description showing possession of the necessary functional characteristics that correlate between each claimed protein and A2 sequence for detection. In particular, immunoprecipitation-mass spectrometry would also detect indirect protein interactions with A2 sequence. Because the specification has not identified the structural characteristics that A2 sequence directly binds to the claimed proteins (as each claimed proteins have different structures) and the assay is through immunoprecipitation, the skilled artisan would not be able to conclude that if the claimed protein is the only element in a sample, then it would have the structural ability to directly bind to the A2 sequence.
Given the claimed broadly class of samples and in the absence of sufficient disclosure of relevant identifying characteristics for said samples, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014) and the specification at best describes plan for making fusion proteins encompassed by the “limitations above” and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)). Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.).
The instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the claimed genuses or structural common to the members of the genuses so the one of skill in the art can visualize or recognize the member of the genus for binding.
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In conclusion, there is nothing in the application as filed that discloses a representative of species. As written, the claims encompass generic structures for desired functional properties, namely the binding between SLYGSSRHTAPISF (A2) and said protein in any sample that that only requires one claimed protein. Because the only disclosed detection is through immunoprecipitation-mass spectrometry which collects all the protein directly and indirectly associated to A2 sequence, a skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the claimed genus. The specification does not evidence the possession of these genuses that are undefined and uncharacterized falling within the potentially large genus to establish possession. Consequently, Applicant was not in possession of the instant claimed invention. The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
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 1-3 and 7-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11789029B2 in view of Khan et al. (US8541550B2, published 09/24/2013).
Instant claim 1, Patent claim 1 recites a peptide having less than 30 amino acid residues comprising a recognition sequence selected from the group consisting of: SLYGSSRHTAPISF (SEQ ID NO. 2). Further, Patent claim 9 recites a method of identifying a site of brain injury in a subject comprising administering to the subject a targeting peptide comprising a recognition sequence selected from the group consisting of SLYGSSRHTAPISF (SEQ ID NO. 2) wherein the targeting peptide has less than 30 amino acid residues; detecting the targeting peptide at a site in the brain of a subject; and identifying the site of brain injury in the subject at the site the targeting peptide is detected in the brain of the subject.
Even though the Patent claims recite identifying a site of brain injury in a subject, the Patent claims do not explicitly recite the claimed proteins of instant claims 1-3.
Khan teaches methods and compositions with polynucleotide-binding polypeptides or polynucleotide-packaging polypeptides having a PTD and optionally a targeting signal or domain (see col. 7, lines 55-65). Khan teaches proteins that have mitochondria localization signals for targeting linked proteins or nucleic acid to the mitochondria (see Table 1). Khan teaches in Table 1, for example, mitochondria succinate-CoA ligase beta subunit, mitochondria citrate synthase homology, glutamine chain synthetase, mitochondrial synthase, and pyruvate dehydrogenase. Importantly, Khan teaches that neurodegenerative brain conditions have been associated with mitochondrial dysfunction (see col. 36, lines 23-25).
First, it would have been obvious to a person at the time of filing to have used the SEQ ID NO: 2 recited in Patent claim 1 for protein detections because Patent claim 9 recites that SEQ ID NO: 2 identifies the site of brain injury in a subject by detecting the targeting peptide at a site in the brain of a subject. Therefore, it would have been obvious to the person to identify sites of brain injury by detecting proteins of a brain sample with neurodegenerative brain conditions because Khan teaches that proteins in Table 1 are mitochondrial proteins or associated with mitochondria to produce localized signals and neurodegenerative brain conditions have been associated with mitochondrial dysfunction. The person would have reasonably expected success in using SEQ ID NO:2 for brain injury to detect the claimed proteins because it has been well understood in the art to use peptides to detect proteins for neurodegenerative conditions, as taught by Khan.
Instant claims 2-3, as stated above the Patent claims do not recite the claimed protein. Khan teaches proteins that have mitochondria localization signals for targeting linked proteins or nucleic acid to the mitochondria (see Table 1). Khan teaches in Table 1, for example, mitochondria succinate-CoA ligase beta subunit, mitochondria citrate synthase homology, glutamine chain synthetase, mitochondrial synthase, and pyruvate dehydrogenase.
Instant claims 7-8, Patent claim 19 reads on the claimed targeting peptide as Patent claim 19 recites a biotin scaffold having the sequence: SEQ ID NO. 10 X1-X2-(X3-X4-)-G-S-K-S-E-K(Biotin)-G-PropargylG wherein: X1 and X3 each is any amino acid, and X2 and X4 each is any amino acid, and the target peptide and the at least one second targeting peptide further comprise a cysteine residue at the C-terminus and N-terminus, wherein X1 and X3 of the biotin scaffold each forms a bond with the N-terminal cysteine and the C-terminal cysteine of the target peptide and the at least one second targeting peptide.
Instant claims 9-11, Patent claims 6-8 read on the instant claimed X1-X4.
Instant claims 12-13, Patent claims 11-12 recite brain tissue sample.
Response to Arguments
Applicant's arguments filed 12/26/2025 have been fully considered but they are not persuasive. Note that the written description has been modified in view of the amendments. The written description is related to the sample as claimed.
Applicant argues on page 7 that the disclosure includes an embodiment that was actually reduced to practice through immunoprecipitation-mass spectrometry (IP-MS) results using A2 and lysates from controlled cortical impact (CCI) and sham surgeries. IP-MS analysis identified 17 proteins specific to the injury condition when using A2 sequence. Martinez (referenced) discloses the exact same results in supplementary Table S4. Such evidence of actual reduction to practice reasonably conveys to one of ordinary skill in the art that the inventor had possession of the invention.
The arguments are not found persuasive for the following reasons. As stated above, the written description is related to the generic sample that is being used against the A2 sequence. Although IP-MS analysis identified 17 proteins as claimed (see Table 6 of specification or Table S4 of Martinez), the specification discloses a specific TBI samples containing acute stage to use A2 sequence for measurements through immunoprecipitation-mass spectrometry for protein detection. In particular, immunoprecipitation-mass spectrometry would also detect indirect protein interactions with A2 sequence. Because the specification has not identified the structural characteristics that A2 sequence directly binds to the claimed proteins (as each claimed proteins have different structures) and the assay is through immunoprecipitation, the skilled artisan would not be able to conclude that if the claimed protein is the only element in a sample, then it would have the structural ability to directly bind to the A2 sequence.
With respect to the nonstatutory double patenting rejection, Applicant has requested that the double patenting rejection be held in abeyance until all other rejections have been addressed and withdrawn.
The argument is not found persuasive. Because a terminal disclaimer has not been filed and the amendments have not overcome the rejection, the nonstatutory double patenting rejection over Patent 8541550 in view of Khan is maintained.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678