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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 14, 2026, has been entered.
Status of the Claims
Claims 11-16 and 19-22 are pending. Claim 11 was amended, and claims 19-22 were added in the response filed May 14, 2026.
Claim Rejections - 35 USC § 101 - Withdrawn
The rejection of claims 11 and 14-16 under 35 U.S.C. 101 is withdrawn. The rejection does not apply to new claim 19. The declaration under 37 CFR 1.132 filed May 14, 2026, by Dr. Sazid Hussain is sufficient to overcome the rejection. The declaration presents evidence that the claimed peptide is markedly different from the corresponding protein in nature, trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU). The declaration states in para. 7 that the CAQK sequence in the trypsin inhibitor is structurally constrained within a reactive site loop in the three dimensional structure of the protein. As a result of this structural constraint, the CAQK sequence in the trypsin inhibitor is unable to bind the CPSG rich extracellular matrix complex, treat acute brain injury, or home to a site of acute brain injury, as required by the claims and as demonstrated in the specification. Based on this evidence, the claimed peptides are markedly different from their naturally occurring counterparts (trypsin inhibitor from Acaris suum), and thus are not natural phenomenon exceptions.
Claim Rejections - 35 USC § 101 - New
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 21-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomemon without significantly more.
Claim interpretation: this rejection is based on interpretation 2 presented in the 112(b) rejection below wherein “the composition” in claim 21 means “the isolated peptide” and the scope of the isolated peptide includes peptides that are longer than four amino acid residues in length that include a tetrapeptide consisting of CAQK embedded within its sequence.
Step 1: Claim 21 is to a composition of matter.
Peptide that are longer than four amino acid residues in length that include a tetrapeptide consisting of CAQK embedded within its sequence are naturally-occurring, for example trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU). The characteristics of isolated trypsin inhibitor from Ascaris suum are not markedly different than the corresponding protein in nature because the peptide and its counterpart have the same chemical structure, amino acid sequence, and function. There is no evidence that isolation changes the structural or functional properties of trypsin inhibitor from Ascaris suum.
Step 2A, Prong 1: Claim 21 is directed to a product of nature, the peptide trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU), which is longer than four amino acid residues in length and includes a tetrapeptide consisting of CAQK embedded within its sequence. The closest counterpart to the nature-based product is the peptide trypsin inhibitor in Ascaris suum. The claimed peptide is isolated. However, the claimed peptide is otherwise structurally and functionally identical to the natural peptide, e.g., it has the same peptide backbone and amino acid sequence and function as tyrpsin inhibitor in nature. This difference is not a marked difference. In addition, the claim does not require any particular function. In sum, the claimed peptides are different, but not markedly different, from their naturally occurring counterparts, and thus are natural phenomenon exceptions
Step 2A, Prong 2: The claim only recites the peptide, which is a natural phenomenon exception. Because there are no additional claim elements besides the judicial exception, the judicial exception is not integrated into a practical application (MPEP § 2106.04(d)(III)).
Step 2B: The claim only recites the peptide, which is a natural phenomenon exception. Because there are no additional claim elements besides the judicial exception, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05).
Therefore, claim 21 is patent ineligible.
Regarding claim 22, BRI includes the trypsin inhibitor from Ascaris suum in water.
Step 1: Claim 22 is to a composition of matter.
Step 2A, Prong 1: Claim 22 is directed to a product of nature, the peptide trypsin inhibitor from Ascaris suum and the pharmaceutically acceptable carrier, which may be a nature-based product such as water. Because the peptide and water as claimed are not found together in nature, the closest counterpart to the nature-based products is trypsin inhibitor from Ascaris suum and water. As determined in the analysis of claim 21 above, the claimed peptide is different, but not markedly different from trypsin inhibitor from Ascaris suum. There is no evidence on record that mixing the claimed peptide with water changes the structure, function, or other properties of either the peptide or water in a marked way. Thus, for at least one embodiment of the claim with the BRI (e.g. wherein the carrier is water), the claimed mixture as whole does not display markedly different characteristics compared to the naturally-occurring counterparts. Instead, the peptide and water have the same characteristics in the mixture as the individual components, the same chemical structure and the same function of inhibiting trypsin and being a solvent. See Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Accordingly, each component, the peptide and the carrier, is a natural phenomenon exception.
Step 2A, Prong 2: The claim only recites the peptide and the carrier, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exceptions, the judicial exceptions are not integrated into a practical application (MPEP § 2106.04(d)(III)). In addition, because the limitation “pharmaceutically acceptable” 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)).
Step 2B: Prior to applicant’s invention and at the time of filing the application, using a carrier for a peptide was well-understood, routine, and conventional. Because mixing the peptide with a carrier at this high level of generality does not meaningfully limit the claim, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05). In addition, because the limitation “pharmaceutically acceptable” 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)).
Therefore, claim 22 is patent ineligible.
Claim Rejections - 35 USC § 112(a) - Maintained
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, 19, and 21-22 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 consisting of CAQK or for using the full scope of peptides comprising CAQK, including in a modified form. 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
Claims 11-16 and 19 are drawn to compositions comprising a peptide of 50 amino acids or less comprising CAQK, wherein the composition does not comprise a cargo. The peptide treats acute brain injury, selectively homes to the site of acute brain injury, or binds a CSPG rich extracellular matrix complex.
The breadth of the claims
Regarding claims 11-16 and 19, 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 of treating brain injury, selectively homing to a site of brain injury, or binding a CSPG rich extracellular matrix complex. The amino acids other than the CAQK tetrapeptide may be any of the 20 naturally-occurring amino acids or any non-natural amino acid. The amino acids may be N- and/or C-terminal to the CAQK tetrapeptide. As evidenced by claim 12, the scope of the claims also includes any type of chemical modification of the peptide, including to its side chains and backbone. The number of species that meet the structural requirements of the genus are enormous. The intended use of the composition includes treating all types of brain injury such as those resulting from traumatic brain injury, stroke, and combinations thereof, homing to the site of brain injury, and binding a CSPG rich extracellular matrix complex.
Regarding claims 21-22, this rejection is based on interpretation 2 presented in the 112(b) rejection below wherein “the composition” in claim 21 means “the isolated peptide” and the scope of the isolated peptide includes peptides that are longer than four amino acid residues in length that include a tetrapeptide consisting of CAQK embedded within its sequence. The specification suggests a use for these peptides in treating all types of brain injury such as those resulting from traumatic brain injury, stroke, and combinations thereof, homing to the site of brain injury, and binding a CSPG rich extracellular matrix complex.
The State of the Prior Art
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.
The declaration under 37 CFR 1.132 filed May 14, 2026, by Dr. Sazid Hussain presents evidence that underscores the level of unpredictability in the art. The peptide trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU) is an example of a peptide that is longer than four amino acids in length but that comprises CAQK. The declaration states in para. 7 that the CAQK sequence in the trypsin inhibitor is structurally constrained within a reactive site loop in the three dimensional structure of the protein. As a result of this structural constraint, the CAQK sequence in the trypsin inhibitor is unable to bind the CPSG rich extracellular matrix complex, treat acute brain injury, or home to a site of acute brain injury, as required by the claims and as demonstrated in the specification. The extent to which the three dimensional structure of the peptide in which the CAQK sequence is embedded affects the function of the CAQK tetrapeptide is unpredictable.
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 acute brain injuries or for selectively homing to a site of brain injury, wherein the CAQK is embedded in a peptide of up to 50 amino acid in length. The role of the up to 50 amino acids N- and/or C-terminal to the CAQK motif on the overall fold, stability and dynamics of the peptide are not described. The specification also does not describe how modifying the side chains and/or backbone of the peptide will affect function. As a result, it is impossible to predict, based on the specification, how adding amino acids up to a length of 50 or modifying the peptide will affect the ability to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex.
The Presence or Absence of Working Examples
The specification discloses the actual reduction to practice of administering the CAQK tetrapeptide 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 the CAQK tetrapeptide 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 peptides, which include peptides of up to 50 amino acids in length. Therefore, it is not possible to discern from the data on these models alone whether the full scope of the genus of peptides comprising CAQK, which includes peptides longer than the tetrapeptide, as well as modified peptides, can be used to treat acute brain injury, home to a site of brain injury, or bind a CSPG rich extracellular matrix complex.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if peptides comprising CAQK that are longer than a tetrapeptide and/or are modified can be used for the claimed 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. Applicant has not adequately addressed the issue pertaining to the length of the claimed peptides.
Claim Rejections - 35 USC § 112(a) - New
Claims 11-16 and 19 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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 drawn to compositions comprising a peptide of 50 amino acids or less comprising CAQK, wherein the composition does not comprise a cargo. The peptide treats acute brain injury, selectively homes to the site of acute brain injury, or binds a CSPG rich extracellular matrix complex. 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 functions. The amino acids other than the CAQK tetrapeptide may be any of the 20 naturally-occurring amino acids or any non-natural amino acid. The amino acids may be N- and/or C-terminal to the CAQK tetrapeptide. Regarding claim 12, the peptide can be modified in any way at any side chain or at the backbone of any residue.
Only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, the claim encompasses all of the sequences meeting the structural requirements that are also able to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex. Although with the aid of a computer it may be possible to determine the amino acid sequences of the peptides that meet the structural requirements of the claim (i.e. up to 50 amino acids in length and comprising CAQK), it is not readily apparent from the claims or the specification which of these sequences are also able to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex.
The specification discloses the actual reduction to practice of administering the CAQK tetrapeptide 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 the CAQK tetrapeptide 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 peptides, which include peptides of up to 50 amino acids in length as well as modified peptides. Therefore, one of ordinary skill in the art would not consider the tetrapeptide CAQK to be representative of the full scope of the claimed genus.
The specification does not disclose a partial structure of a protein that meets the structural requirements of the genus. Although from the statement “50 amino acids or less, which includes the amino acid sequence CAQK” one of ordinary skill in the art could determine if a given amino acid sequence meets the structural requirements of the genus, it would not be possible to determine from the sequence alone if the protein is able to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex. Unless all sequences having up 50 amino acids or less, which includes the amino acid sequence CAQK are able to perform these functions, this description alone does not constitute a partial structure for the genus.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the brain injury, homing, and CSPG rich extracellular matrix complex binding activity and therefore do not describe which additions to the N- and/or C-terminal of CAQK could be made while preserving function. The specification does not describe how a folded, three-dimensional peptide structure could impact function. Understanding the physical basis for the claimed function is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the up to 50 amino acids N- and/or C-terminal to the CAQK motif on the overall fold, stability and dynamics of the peptide are not described. As a result, it is impossible to predict, based on the specification, how adding amino acids up to a length of 50 will affect the ability to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex.
Solid state peptide synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could isolate, albeit with route experimentation and optimization, a peptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the peptide to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the structural requirements of the claims would also be able to treat acute brain injury, selectively home to the site of acute brain injury, and/or bind a CSPG rich extracellular matrix complex. The specification does not make clear which peptides are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which peptides to make.
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.
The declaration under 37 CFR 1.132 filed May 14, 2026, by Dr. Sazid Hussain presents evidence that underscores the predictability in the art. The peptide trypsin inhibitor from Ascaris suum (Uniprot P19398 · ITR1_ASCSU) is an example of a peptide that is longer than four amino acids in length but that comprises CAQK. The declaration states in para. 7 that the CAQK sequence in the trypsin inhibitor is structurally constrained within a reactive site loop in the three dimensional structure of the protein. As a result of this structural constraint, the CAQK sequence in the trypsin inhibitor is unable to bind the CPSG rich extracellular matrix complex, treat acute brain injury, or home to a site of acute brain injury, as required by the claims and as demonstrated in the specification. The extent to which the three dimensional structure of the peptide in which the CAQK sequence is embedded affects the function of the CAQK tetrapeptide is unpredictable.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention. In conclusion, only the unmodified CAQK tetrapeptide that does not comprise a cargo, satisfies the written description requirements of 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 112(b) - New
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 20 is indefinite because it depends from claim 1, which is canceled.
Claim 21 recites the limitation "within the composition". There is insufficient antecedent basis for this limitation in the claim. The claim nowhere recites a composition prior to the limitation “within the composition”. In addition, claim 21 is an independent claim and therefore does not refer to a composition in another claim. Because of the lack of antecedent basis two plausible interpretations of the claim are possible: 1) the scope of the isolated peptide in claim 21 is limited to peptides that are four amino acid residues in length consisting of the amino acid sequence CAQK, and the isolated peptide is within a composition that may include other, unrecited elements; and 2) “the composition” means “the isolated peptide” in which case the scope of the isolated peptide in claim 21 includes peptides that are longer than four amino acid residues in length that include a tetrapeptide consisting of CAQK embedded within its sequence.
Claim 22, which depends from claim 21, fails to remedy this issue and is likewise rejected.
Claim Rejections - 35 USC § 112(d) - New
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 20 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 20 depends from claim 1, which is cancelled. As a result, claim 20 fails to include all the limitations of the claim upon which it depends. 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.
Claim Rejections - 35 USC § 102 - Maintained
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, 14-16, 19, and 21-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Germond (US 2004/0071714 A1). This rejection has been modified to reflect the amendment filed May 14, 2026.
Germond teaches a composition comprising a linear 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. Therefore, the composition of Germond meets all of the structural limitations of claim 11.
Regarding claim 14, Germond teaches combining the peptides of Figure 1 with a pharmaceutically acceptable carrier (Example 1, para. [0049], [0053]).
Regarding claim 19, the peptides in Germond are linear.
Claim interpretation: The limitation “wherein: a. the peptide treats acute brain injury; b. the peptide selectively homes to a site of acute brain injury or acute spine injury; or c. the peptide binds a CSPG rich extracellular matrix complex” in claim 11 is a functional and/or intended use limitation.
MPEP § 2112.01(II) states: "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In the instant case, the prior art teaches a composition comprising a linear peptide that is less than 50 amino acids in length, that comprises the sequence CAQK, and that does not contain a cargo, combined with a pharmaceutically-acceptable carrier (Peptide T5 NH2-ENGECAQK-OH and Peptide T11 NH2-WENGECAQK-OH, emphasis added, in Figure 1) but is silent as to the ability of the peptide to treat acute brain injury, selectively home to a site of acute brain injury, or bind to a CSPG rich extracellular matrix complex. Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed properties of treating acute brain injury, selectively homing to a site of acute brain injury, or binding to a CSPG rich extracellular matrix complex are inherent to the prior art composition. The inventors have found a new property of an old composition. Such a discovery does not constitute a new composition.
Furthermore, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the prior art composition must be capabable of performing the claimed intended use of treating acute brain injury, selectively homing to a site of acute brain injury, or binding to a CSPG rich extracellular matrix complex are inherent to the prior art composition.
Therefore, Germond anticipates claims 11, 14-16, and 19.
Regarding claim 21, this rejection is based on interpretation 2 presented in the 112(b) rejection above wherein “the composition” means “the isolated peptide” and the scope of the isolated peptide includes peptides that are longer than four amino acid residues in length that include a tetrapeptide consisting of CAQK embedded within its sequence. Peptide T5 NH2-ENGECAQK-OH and Peptide T11 NH2-WENGECAQK-OH (emphasis added) (Figure 1) each meet this criteria and therefore anticipate the claim.
Regarding claim 22, Germond teaches combining the peptides of Figure 1 with a pharmaceutically acceptable carrier (Example 1, para. [0049], [0053]).
Response to Arguments
Applicant's arguments filed May 14, 2026, have been fully considered but they are not persuasive.
Applicant traverses the rejection on the grounds that Germond supports a position that CAQK can be found in longer peptide sequences but nowhere discloses that the peptides treat acute brain injury, selectively home to a site of acute brain injury, or bind a CSPG rich extracellular matrix. This argument is not persuasive because the wherein clause in claim 11 is interpreted as a function and/or intended use limitation. Because the prior art meets the structural limitations of the claims, the wherein clause is inherently met.
Claims 20-21 do not recite any functional or intended use limitations and are rejected accordingly.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 16/770,041, PCT/US2018/064290, 62/595,797, 16/859,893, 15/756,947, PCT/US2016/50168, and 62/213,168, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. For the same reasons presented in the 112a enablement and written description rejections above, the prior-filed disclosures are insufficient to support the full scope of the claimed genus of peptides, which include peptides of up to 50 amino acids in length, and having any modification.
The earliest effective filing date of claims 11-16 and 19 is the filing date of the instant application, May 27, 2022.
Regarding claims 21-22, claim interpretation 2 presented in the 112(b) rejection above, includes CAQK embedded in longer peptides. For the same reasons presented in the 112a enablement rejections above, the prior-filed disclosures are insufficient to support the full scope of the claimed genus of peptides, which include peptides of length. The earliest effective filing date of claims 21-22 is the filing date of the instant application, May 27, 2022.
Claim Rejections - 35 USC § 102 - New
Claims 11-12, 14-16, 19, and 21-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mann et al. (NPL 6, IDS 6/19/2022), published June 28, 2016.
Mann et al. teach an aqueous solution of the tetrapeptide CAQK (p. 10, col. 1, para. 3). The peptide is in aqueous solution prior to conjugation and therefore does not include a cargo composition or cargo molecule. Mann et al. satisfy all of the structural limitations of claims 11 and 21. The functional properties recited in claim 11 and in dependent claims 15-16 are inherent to the structure. Therefore, Mann et al. anticipate claims 11, 15-16, and 21.
Regarding claim 12, Mann et al. also teach the tetrapeptide CAQK in protected form during solid-phase peptide synthesis (p. 9, col. 1, para. 2). The CAQK plus protecting groups constitutes a modified peptide.
Regarding claims 14 and 22, aqueous solution is a pharmaceutically-acceptable carrier.
Regarding claim 19, the peptide is linear.
Double Patenting - Maintained
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, 19, and 21-22 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. This rejection has been modified to reflect the amendment filed May 14, 2026. Applicant did not traverse this rejection or file a terminal disclaimer.
Patented claim 5 recites a composition comprising an isolated peptide and a pharmaceutically acceptable carrier, wherein the peptide consists of 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, 14, and 21-22.
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.
Regarding claim 19, the peptide is linear.
Conclusion
No claims are allowed.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/Primary Examiner, Art Unit 1654
