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.
Status of Claims
Claims 1, 4 and 7-19 are pending. Claims 4 and 17-19 are withdrawn. Claims 14-19 are new. Claims 2-3, and 5-6 are canceled. Claims 1 and 7-16 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 and 7-16 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 the claimed proteins by obtaining a sample from neural tissue; contacting a sample derived from neural tissue with a target peptide comprising a recognition sequence of SLYGSSRHTAPISF (SEQ ID NO. 2) and having less than 30 amino acid residues; and detecting binding between the targeting peptide and said protein.
The claims as a whole cover a genus of claimed proteins that simply binds to SLYGSSRHTAPISF sequence (SEQ ID NO: 2) in a sample that is derived from neural tissue samples or neural tissue samples. Explicit in the claims is a method for detecting binding between the target peptide comprising SEQ ID NO: 2 and said proteins which invokes possessions of certain functional characteristics; namely, the structural characteristics of these proteins and SEQ ID NO: 2.
Level of skill and knowledge in the art:
Martinez et al. disclose 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, i.e., claimed SEQ ID NO: 2). 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). Martinez teaches immunoprecipitation-mass spectrometry is the only process to collect and determine the proteins of neural tissue samples with A2 sequence (see pg. 13, para. 2). (“Uncovering temporospatial sensitive TBI targeting strategies via in vivo phage display”, Science Advances, vol., 8, eabo5047, published 2022, see 892 dated 01/15/2026).
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). In particular, the specification discussed that although dAb production and purification were successful for two 1dpi aABs as measured by positive histidine-tag Western blots, they failed to show bioreactivity to injured tissue via immunohistochemistry (see para. [0076], as filed). The specification discloses IP-MS analysis is required for the identification of 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 (see para. [0078], as filed). Additionally, the specification discloses the high volume of peptides recovered by MS and their involvement in highly represented pathways suggest that they are the most probable targets of the A2 and SA1 (see para. [0079], as filed). The specification also discloses the proteins identified by A2 HCDR3 were highly implicated in metabolic dysfunction, but overall citrate synthase and succinate-CoA ligase β were determined to be most prevalent due to their involvement in the processes identified from pathway analysis and number of peptides recovered via mass spectrometry (see para. [0080], as filed).
In other words, the specification discloses a specific process that detects the binding between SEQ ID NO: 2 (i.e., A2) and the claimed sample. Meanwhile, the instant application has not provided a sufficient description showing possession of the necessary functional characteristics that correlate between A2 sequence and each claimed protein. Also, these proteins do not share any structural similarities for a single sequence to bind. Because the specification has not identified the structural characteristics that A2 sequence can directly or indirectly bind to all the claimed proteins coupled with the lack of a representative number of disclosed processes for analyzing the claimed neural tissue sample, at this stage of using A2 sequence for detection, the skilled artisan would not be able to conclude detecting the claimed proteins with SEQ ID NO. 2 without structural similarities between said proteins.
Given the claimed broadly class of proteins and in the absence of sufficient disclosure of relevant processes for detecting with a single A2 sequence, 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 with respect to the process being performed. As written, the claims encompass generic structures for desired functional properties, namely SLYGSSRHTAPISF (A2) has the ability to directly bind to a broad set of proteins that do not share common structural features. 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 does 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 and 7-16 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. Patent claim 11 recites brain tissue sample.
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 claims 9 and 11 recite 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 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.
Instant claims 14-16, Patent claim 12 recites the brain tissue sample is the site of acute brain injury.
Response to Arguments
Applicant's arguments filed 04/15/2026 have been fully considered. Although the written description has been modified in view of the amendments, the arguments are not persuasive.
Applicant argues on page 6 that amended claim 1 does not require the targeting peptide to directly bind to each listed protein in order to practice the claimed method. Applicant argues that the Examples demonstrate to a person in the art that SEQ ID NO: 2 is suitable for use to specifically identify pathology associated with the acute stage of traumatic brain injury.
The arguments are not found persuasive for the following reasons. Although the claims require the sample from neural tissue, the question to establish is that these proteins do not share any common feature between one another. The claim recites that the process is detecting binding between a single sequence against all these proteins. Thus, a single sequence would not be necessarily capable of all indirectly or directly binding to said proteins. Importantly, the specification and Martinez disclose that to identify these proteins from a neural tissue sample, immunoprecipitation-mass spectrometry is required or the SEQ ID NO: 2 (A2) binds to specific proteins identified in Table 2 of Martinez (page 7). Also, “a sample from neural tissue” (as claimed) would encompass a sample that only contains, for example, only one of the claimed proteins (i.e., a sample derived from neural tissue). What is the structure-function relationship of said proteins that is binding against a single sequence? Meanwhile, the claim encompasses direct binding.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAM P NGUYEN whose telephone number is (571)270-0287. The examiner can normally be reached Monday-Friday (8-4).
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, Gregory Emch can be reached at (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
Prosecution Insights