DETAILED ACTION
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 .
Status of the Claims
Claims 1-16 are pending. Claim 11 was amended and claims 17-18 were cancelled in the response filed October 17, 2025.
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 24, 2025.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 11 and 14-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claims recite a composition comprising a peptide of 50 amino acids or less which includes CAQK. A peptide of 50 amino acids or less which includes CAQK is a fragment of numerous naturally-occurring proteins, including trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU). The structural characteristics of peptides of 50 amino acids or less including CAQK in the claims are not markedly different than the corresponding proteins in nature because the peptides and their counterparts have the same chemical structure and amino acid sequence. The claimed property of treating acute brain or acute spine injury, homing to the site of acute brain or spine injury, and/or binding a CSPG rich extracellular matrix complex is innate to the amino acid sequence itself, and is not created or altered by truncating the peptides from the naturally-occurring counterparts. The composition may include a pharmaceutically acceptable carrier such as water, which is also naturally-occurring. There is no evidence that the protein and the carrier differ from their naturally-occurring counterparts when combined in the composition. This judicial exception is not integrated into a practical application because although an intended use is claimed, the actual composition as it physically exists is not limited to any particular use. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because only the peptide in a composition of the natural-occurring peptide and carrier is claimed. Therefore, claims 11 and 14-18 are ineligible. Regarding claim 12, the claim encompasses natural-occurring post-translational modifications of CAQK-containing proteins.
Response to Arguments
Applicant's arguments filed October 17, 2025, have been fully considered but they are not persuasive.
First, Applicant traverses the rejection on the grounds that an amino acid sequence of 50 amino acids or less and comprising CAQK is markedly different from a peptide found in nature on a structural basis. For example, trypsin inhibitor from Acaris suum is 62 amino acids in length. The claimed peptide has a different structural characteristic than the natural peptide, i.e., the natural peptide has covalent bonds on its ends that connect it to the rest of the protein whereas the claimed peptide lacks these bonds. However, the claimed peptide is otherwise structurally identical to the natural peptide, e.g., they had the same peptide backbone and amino acid sequence as trypsin inhibitor from Acaris suum in nature. This difference is not a marked difference in view of MPEP § 2106.04(c)(II)(C)(2) and the Supreme Court decision in Myriad. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977. In addition, the function of the claimed peptide, is innate to the peptide itself, and was not created or altered by the inventor. See Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, the claimed peptides are different, but not markedly different, from their naturally occurring counterparts (trypsin inhibitor from Acaris suum), and thus are natural phenomenon exceptions.
Next Applicant argues that the claimed properties provide significant utility. This argument is not persuasive. Because the limitation treats acute brain or acute spine injury, homes to the site of acute brain or spine injury, and/or binds a CSPG rich extracellular matrix complex does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)). In addition, these intended uses are not significantly more than the judicial exception.
For these reasons, the rejection is maintained.
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 11-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating traumatic brain injury with a composition comprising a peptide consisting of CAQK, wherein the composition does not contain a cargo and wherein the tetrapeptide is the therapeutic agent, does not reasonably provide enablement for treating all other nervous system injuries with a peptide comprising CAQK. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention
The claims are drawn to compositions comprising a peptide comprising CAQK, wherein the composition does not comprise a cargo. The peptide treats acute brain or spine injury, selectively homes to the site of acute brain or spine injury, or binds a CSPG rich extracellular matrix complex.
The breadth of the claims
The scope of the peptides in the claimed compositions include the tetrapeptide CAQK and all peptides and polypeptides up to 50 amino acids in length that comprise CAQK and have the required function.
The intended use of the composition includes treating all types of brain and spine injury such as a central nervous system injury, aa brain injury, a spinal cord injury, a neural injury, a neuronal injury, or combinations thereof. The nervous system injury includes those resulting from traumatic brain injury, stroke, and combinations thereof.
The State of the Prior Art
The Examiner is not aware of prior art disclosing the use of the claimed compositions to treat nervous system injuries in the absence of cargo. The tetrapeptide CAQK is known in the prior art as being capable of delivering cargo to the site of traumatic brain injury but is not known to be therapeutically active on its own.
The post-filing date art of Mann et al. (NPL 6, IDS 6/19/2022) teaches that CAQK was identified by in vivo phage display screening in mice with acute brain injury (Figure 1). Mann et al. teach that CAQK selectively binds to injured mouse and human brain, and homes to the site of brain injury in mouse models (Figure 2). Mann et al. teach that coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles (Figures 4-5). Mann et al. does not teach that the CAQK tetrapeptide has therapeutic activity in the absence of a cargo.
This teaching is corroborated by Huang (CN 106674328 A), which discloses brain targeting peptides comprising CAQK including: CAQK (SEQ ID NO: 1); CAQKCAQK (SEQ ID NO: 2); CAQKCAQKCAQK (SEQ ID NO: 3); and CAQKCAQKCAQKCAQKCAQK (SEQ ID NO: 4). Huang states that the polypeptides themselves do not have physiological activity (paragraph [0034]).
The Predictability or Unpredictability of the Art
The prior art pertaining to the use of the CAQK tetrapeptide as a therapeutic agent for treating nervous system injuries is highly unpredictable.
Mann et al. state that CAQK enhances the accumulation of systematically administered payloads with a variety of imaging and therapeutic functions of potential utility in clinical management of brain injuries (page 5, column 1, paragraph 3). The use of the tetrapeptide CAQK as a targeting or homing moiety for traumatic brain injury is established. However, the reference is silent with respect to the use of CAQK as a discrete therapeutic agent as claimed.
Even as a homing moiety, Mann et al. suggest that there is a significant level of unpredictability. Although Mann et al. utilize two models, one for gun or shrapnel wounds and one for traumatic brain injury, the reference states (page 5, column 1, paragraph 1): “It remains to be tested whether CAQK also homes to spinal cord injuries...” Therefore, the reference establishes that data from the penetrating brain injury model and the blunt cortical impact model cannot be used to predict the behavior of the peptide in all nervous system injuries.
The Level of Guidance in the Specification
The specification does not describe a general correlation between structure and function for the tetrapeptide CAQK and the treatment of all nervous system injuries.
The Presence or Absence of Working Examples
The specification discloses the actual reduction to practice of administering CAQK in mouse models for penetrating brain injury and traumatic brain injury (Example 1, Materials and Methods) for the examination of the biological effect of the tetrapeptide itself (Example 5). The specification states that CAQK treated mice showed significantly less neuronal degeneration compared to control groups (paragraph [000182]). This model is not representative of the full scope of the claimed genus of brain and spinal injuries, as evidenced by Mann et al. Therefore, it is not possible to discern from the data on these models alone whether the CAQK tetrapeptide can be used to treat other types of nervous system injuries. In addition, these data are not representative of the full scope of the genus of peptides comprising CAQK, which includes peptides longer than the tetrapeptide.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if the CAQK tetrapeptide can be used to treat other types of spinal injuries and whether peptides comprising CAQK that are longer than a tetrapeptide can be used for this or any purpose. The skilled artisan would be burdened with testing a broad range of animal models. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Response to Arguments
Applicant traversed the rejection on the grounds that the amendment has overcome the rejection. This is not persuasive. The rejection has been updated to reflect the amendment and is maintained.
Claim Rejections - 35 USC § 102 - withdrawn
The rejection of claims 11 and 14-18 under 35 U.S.C. 102(a)(1) as being anticipated by Rothe et al. (CN 102174105) is withdrawn in view of the amendment filed October 17, 2025.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 11 and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Germond (US 2004/0071714 A1).
Germond teaches a composition comprising a peptide that is less than 50 amino acids in length and that comprises the sequence CAQK and a pharmaceutically-acceptable carrier. The peptides are Peptide T5 NH2-ENGECAQK-OH and Peptide T11 NH2-WENGECAQK-OH (emphasis added) (Figure 1). The composition does not contain a cargo.
The composition meets all of the structural limitations of claims 11 and 14-16. Because the structure is the same as the instant claims, the intended use recited in instant claims 11 and 14-16 is inherently met. Therefore, Germond anticipates claims 11 and 14-16.
Regarding claim 14, Germond teaches combining the peptides of Figure 1 with a pharmaceutically acceptable carrier (Example 1, para. [0049], [0053]).
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.
The following rejection was not traversed in the response filed October 17, 2025.
Claims 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,376,303. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Patented claim 1 recites a composition comprising an isolated peptide and a pharmaceutically acceptable carrier, wherein the peptide comprises the amino acid sequence CAQK (SEQ ID NO:4), wherein the composition does not comprise a cargo composition or cargo molecule, wherein the composition selectively homes to a site of the brain injury in the subject thereby treating the brain injury via the peptide at the site of the brain jury, anticipating instant claims 11 and 14.
Regarding claim 12, patented claim 3 requires that the peptide is a modified peptide.
Regarding claim 13, patented claim 4 requires that the peptide is a methylated peptide.
Regarding claim 15, patented claim 6 requires that the brain injury comprises traumatic brain injury, stroke injury, or both.
Regarding claim 16, patented claim 11 requires that the composition reduces neuronal degeneration at the site of the brain injury compared with a control treatment.
Conclusion
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 CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654