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 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.
DETAILED ACTION
Claims 1-3, 5-9, 11-12, 15-16, 19-21, 25, 30, 32-33, and 44 are pending in the instant application.
Priority
This application is a 371 of PCT/US2022/070465, filed on 2/1/2022 which claims priority to the provisional application 63144365 filed on 2/1/2021.
Election/Restriction
After further consideration, there is no longer a search burden for the species of peptoids; thus these species will be examined.
Applicant’s election without traverse of Group I (claims 1-3, 5-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 in the reply filed on 9/23/2025 is acknowledged. Applicant also elected the BBB manipulator as docosahexaenoic acid (DHA), thus claims drawn to nanocarriers or nanoparticles were withdrawn from examination.
Claims 3, 5-7, and 44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/23/2025.
Claims 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 are examined herein.
Information Disclosure Statement
The information disclosure statement (IDS) dated 12/23/2025 complies with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits.
Objections to the Specification/Drawings
The specifications and figures are objected to because the amino acid sequences listed
in the “Brief Description of the Figures” section and their corresponding Drawing lacks a SEQ ID
number for the sequence depicted in Fig. 4.
Correction is required. See MPEP § 608.01(b).
Claim Interpretation
Based on Fig 6, it appears “NSpe” may refer to the peptoid residue, (S)-N-(1-phenylethyl)glycine, shown below. The other acronyms were assumed as shown below for the purpose of applying art. A meaningful interpretation of “Cy5.5 Ahx, Ndec, Ns7e, and Ntridec” could not be performed.
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Notice
Claim 3 depends on claim 7. While the contents of this claim were not examined, it was noticed that claim 3 does not depend on a preceding claim. Pursuant to 35 U.S.C. 112 and 37 CFR 1.75(c), a claim in dependent form must refer only to a claim or claims previously set forth. See MPEP § 608.01(n)(4)(F).
Claim Rejections – 35 USC § 112(b)
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 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 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 1
Claim 1 is drawn to “mild cognitive impairment” wherein “mild” is a relative term that is not defined by the claim or the spec. It is also unclear if this cognitive is or is not related to Alzheimer’s disease. One artisan could interpret this as being the result of fatigue, while another artisan would conclude that this is limited to an early symptom of an underlying neurodegenerative disease. Applicant did not provide a definition of “mild” thus one of skill in the art would not be apprised of the metes and bounds of “mild cognitive impairment”. Dependent claims 2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 8
Claim 8 is drawn to a peptoid comprising the formula H-(NLys-Nspe-Nspe)4-NH2, wherein it is unclear what “Nspe” is referring to in this formula. In one interpretation it is a generic N-linked amino acid (i.e. “N-species”). Alternatively, it could be the acronym for a specific molecule. Applicant did not provide a definition for “Nspe”, thus one of skill in the art would not know what that is referring to, thus rendering this claim indefinite. Furthermore, the use of “is” makes it unclear if one should interpret this as the peptoid “consisting of” or merely “comprising” H-(NLys-Nspe-Nspe)4-NH2. As a result of these multiple interpretations, this claim is rendered indefinite.
Claim 9
Claims 9 is drawn to “homologs thereof” and “isomers thereof” wherein applicant has also specified “natural a-amino acid side chain moieties”. Applicant did not provide a definition of “isomers thereof” or “homologs thereof”. In one interpretation, an isomer of N-Leucine is N-Isoleucine. Whereas another artisan may think this extends to 5-bromo-L-isoleucine, or even Leucine. As a result of these multiple interpretations, one of skill in the art would not be apprised of the metes and bounds of these claims, thus rendering these claims indefinite. Dependent claims 11-12, 15-16, 19-21, 25, 30, and 32-33 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 15-16
Regarding claims 15 and 16, it is unclear what the metes and bounds of “C6 to C18” are and the term “about”. Firstly, it is unclear if this definition applies to all carbons in the peptoid monomer (Cn+2), or if it refers to the side chain only (Cn). For example, N leucine could be interpreted as being either C4 or C6. Secondly, applicant did not provide a definition of “about” thus one of skill in the art would not be apprised of the metes and bounds of this term.
Claim 25
Claim 25 recites the limitation “the hexamer" of claim 19. There is insufficient antecedent basis for this limitation in the claim. It is also unclear if applicant is referring to a section of six peptoid residues in a larger peptoid chain, or if applicant is intending to claim that the peptoid consists of six peptoid residues. Because of these multiple interpretations, this claim is rendered indefinite.
Claim 33
Claim 33 is drawn to several peptoid structures wherein it is unclear what Nspe, Nspe(p-Br), Cy5.5, Ahx, Ndec, Ns7e, Ntridec, are referring to. In one interpretation it is a generic N-linked amino acid (i.e. “N-species”). Alternatively, it could be the acronym for a specific molecule (see claim interpretation). Cy5.5 might be a fluorophore. Applicant did not provide a definition for any of these acronyms, thus one of skill in the art would not know what that is referring to, thus rendering this claim indefinite.
Claim 33
Claim 33 is drawn to a list of exemplary peptoids wherein it is unclear if the invention “consists of” one of the cited poly-peptoids or if they merely “comprise” one of the cited poly-peptoids. For example, the poly-peptoid example of “H-(Nlys-Nspe-Nspe(p- Br))2-NH2” lacks variable A (e.g. H-(X-Y-Z)2-B), thus it fails to satisfy the conditions of formula 9, which requires a minimum of four peptoid residues. While one may be tempted to treat this as a fragment of a poly-peptoid, because applicant has included the termini of “-H” and “-NH2” which suggest that applicant intends the “consisting of” definition. Because of this inconsistency, one of skill in the art would not be apprised of the metes and bounds of this claim, rendering it indefinite.
Claim Rejections – 35 USC § 112(d)
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 33 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 33
Claim 33 is drawn to several exemplary peptoids that do not follow the formula of parent claim 9. Claim 9 specifies the formula A-(X-Y-Z)n-B wherein A, X, Y, and Z must be peptoid residues. B is optionally NH2, one peptoid residue, or two peptoid residues. The following species fail to satisfy the formula established in claim 9, which represents an expansion of scope. The “?” symbol in the Table below indicate points of inconsistency in the species and its representation in the formula.
species
formula representation
satisfies formula?
H-(Nlys-Nspe-Nspe)4
?-(X-Y-Z)4-B
n
Cy5.5-Ahx--(Nlys-Nspe-Nspe)4-NH2
?-?-(X-Y-Z)4-B
n
H-(Nlys-Nspe-Nspe(p-Br))2-NH2
?-(X-Y-Z)2-B
n
H-(Ntridec-Nlys-Nspe)-Nspe-Nlys-NH2
A-(X-Y-Z)-B-B-?
n
H-(Nlys-Nspe-Nspe)3-Nlys-Nspe-NH2
?-(X-Y-Z)3-B-B-?
n
H-(Nlys-Nspe-Nspe)2-NH2
?-(X-Y-Z)2-B
n
H-Ndec-(Nlys-Nspe- Ns7e)2-NH2,
A-(X-Y-Z)2-B
y
H- Ndec-(Nlys-Nspe- Nspe(p-Br))2-NH2
A-(X-Y-Z)2-B
y
H- Ntridec-(Nlys-Nspe-Nspe(p-Br))2-NH2
A-(X-Y-Z)2-B
y
Nrpe-N(cypent)-N(4-SO2NH2Bn)-N(Ph2(CH2))-NLys-NLys
A-(X-Y-Z)-B-B
y
N(cypent)-N(cypent)-NLys-NLys-NLys-NLys-NLys-NH2
A-(X-Y-Z)-B-B-?-?
n
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 § 112(a)
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 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 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.
All claims
Claims 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 are drawn to a peptoid conjugate capable of treating Alzheimer’s disease, wherein there is insufficient structure to describe the peptoids possessing the desired function. Applicant can meet the written description requirement by (1) describing an exemplary number of species or (2) by describing the core structure responsible for the peptoid’s function. Applicant has provided a single example (Peptoid 1, Fig 6) which is rationalized as an Alzheimer’s treatment because it is a representative truncated analogue of LL-37, which is known to be effective in treating Alzheimer’s disease. The peptoids described in Table 1 (pg 15) are exemplary anti-bacterial peptoids or non-functional control peptoids discussed in another patent. Given the single example of Peptoid 1, which is prophetic in its function to treat Alzheimer’s disease, the instant specification has failed to meet the written description requirement via representative number of species. Applicant also failed to specify the core structure required of truncated analogues of LL-37 in order to possess the function of treating Alzheimer’s disease. As a result, applicant has failed to meet the written description requirement.
All claims
Claims 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 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 Alzheimer’s disease using Peptoid 1 described in Fig 6, it does not reasonably provide enablement for (i) treating Alzheimer’s disease using any peptoid; or (ii) treating mild cognitive impairment unrelated to Alzheimer’s disease. 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.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention/Breadth of Claims:
The instant invention is drawn to treating Alzheimer’s disease or “mild cognitive impairment” using any peptoid and any BBB-penetrating compound.
State of the prior art/Predictability or unpredictability of the art:
Mandity (doi: 10.1517/17460441.2015.1076790) teaches inhibition of the γ-secretase enzyme leads to effective lowering of the brain β-amyloid concentration, as a means of treating Alzheimer’s disease which is related to the accumulation of β-amyloid plaques (pg 1167, col 2, para 3-4). Mandity teaches acetylated peptoid oligomers of (1S,2S)-aminocyclopentanecarboxylic acid are highly active inhibitors of γ-secretase (pg 1168, col 1, para 1-2). Mandity teaches “The nature and position of the side-chain functionality crucially influenced the inhibitory activity, and the helical secondary structure is therefore a requisite of enzyme inhibitory activity.” (pg 1168, col 1, para 2). Mandity teaches that β-peptide dendrimer conjugates were able to block β-amyloid oligomerization via incorporation of aromatic oligoamides (pg 1168, col 1, para 3). In sum, (i) Alzheimer’s treatments must target either the enzyme that produces AB or target AB itself; and (ii) peptoid-based Alzheimer’s treatments must possess specific primary and secondary structures in order to have this function.
Bezprozvanny (WO2013043669) teaches candidate poly-peptoids were screened for their ability to bind AB42 or AB40 (pg 84, para 00225), then those that bound were subject to a subsequent screen for biological activity in vitro (pg 85, para 00228), then those that passed through those two layers of screening were then subjected to a third screen to see if they exhibited any activity in an Alzheimer’s disease model organism (pg 86, para 00231). Such screening would not have been performed if the inventors new a priori which peptoids would treat Alzheimer’s disease, and which wouldn’t.
Amount of guidance/Existence of working examples:
The instant specification shows that peptoid mimics of LL-37 of the structure shown in Fig 6 slow the kinetics of fibril formation (para 0064). This is the only exemplary peptoid that applicant asserts has the desired function. The peptoids featured in Fig 7-8 have no asserted function or apparent structural similarity to “Peptoid 1” described in Fig 6.
The instant specification provides exemplary peptoids prophesized to have an effect on Alzheimer’s disease, even though they are anti-microbial peptoids (pg 15, Table 1, entries 1-20; pg 14, para 0084). Applicant did not provide an explanation for which antimicrobial peptoids are expected to have the purported function of treating Alzheimer’s disease or why. Applicant also provided control peptoids lacking the function of being antimicrobial, and presumed incapable of treating Alzheimer’s disease (Table 1, entries 21-22), which confirms that not all peptoids have the function of treating Alzheimer’s Disease.
Quantity of experimentation:
Given the structure-function requirement for a peptoid to bind to a specific target (e.g. β-amyloid or γ-secretase) in order to elicit a specific effect (i.e. treat Alzheimer’s Disease), one of skill in the art, in undertaking the experimentation necessary to determine which of the claimed peptoids would be effective, would have no reasonable expectation that the majority of treatments claimed would be successful in treating Alzheimer’s disease. While the disclosure is enabling for the discrete species of Peptoid 1 featured in Fig 6, all other species lack support of possessing the function of treating Alzheimer’s disease. Applicant has provided no evidence or rationale in support of the instant invention being effective in treating all kinds of “mild cognitive impairment.”
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164.
See the decision in Rasmusson v. SmithKline 413 F.3d 1318, 1325 (Fed. Cir. 2005) which stated: “Thus, at the end of the day, the specification, even read in the light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient. [Citation omitted.] ‘If mere plausibility were the test for enablement under §112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the “inventor” would be rewarded the spoils instead of the party who demonstrated that the method actually worked.’”
Therefore, in view of the Wands factors as discussed above, e.g., the amount of guidance provided, the predictability of the art and the lack of working examples, to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections – 35 USC § 102
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 1, 9, 11-12, and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ghosh (WO2019211878).
Claim 1
Regarding claim 1, Ghosh teaches a method for treating Alzheimer's disease by administering effective amount of a peptoid (pg 4, para 9), wherein the peptoid is able to cross the BBB (pg 4, para 6), by virtue of having low molecular weight and high serum stability (pg 17, para 6). This satisfies the limitation of the composition comprising both “a peptoid” and “a BBB manipulator,” as the BBB manipulator is described by function and not structure. There is nothing in the claims that excludes the peptoid as also being a BBB manipulator.
Claim 9, 11-12
Regarding claims 9 and 11-12, Ghosh teaches a peptoid wherein A is a terminal n-alkyl substituted glycine (N-Leu); variable X is proline; variable Y is N-Phe; variable Z is N-Phe; variable B is one N-substituted glycine residue (N-Lys-NH2); and variable n=1, as shown below, wherein proline is chiral.
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Claim 15-16
Regarding claims 15-16, Ghosh teaches A is N-Leu, which comprises six carbons, thus satisfying the limitation of being C6. Ghosh teaches B is N-Lys-NH2, wherein n = 1. Thus satisfying the condition wherein B is N-Lys and B is NH2. See 112(b) rejection above regarding the interpretation of these claims.
Claim Rejections – 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 8-9, 11-12, 15-16, 19-21, 25, 30, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh (WO2019211878) as applied to claims 1, 9, 11-12, and 15-16 above, and further in view of Guo (doi: 10.1016/j.jconrel.2020.09.050), Lee (doi: 10.1016/j.bmcl.2015.04.092), Bezprozvanny (WO2013043669), Molchanova (doi: 10.1038/s41598-020-71771-8), and Gentry (doi: 10.1016/s0196-9781(99)00127-8)
claim 2, 5
Regarding claims 2, 5, Ghosh teaches a method for treating Alzheimer's disease by administering effective amount of a peptoid (pg 4, para 9), wherein the peptoid is able to cross the BBB (pg 4, para 6), by virtue of having low molecular weight and high serum stability (pg 17, para 6).
Ghosh does not teach the BBB manipulator is DHA.
Guo teaches enhancing the permeability of a protease inhibitor called, darunavir, using DHA delivered by nanocarrier, which resulted in enhanced uptake of darunavir into the brain (abstract). Guo teaches HIV causes neurocognitive disorders, thus treatments such as theirs target the viral proteins in the brain (pg 696, col 1, para 1). This satisfies the limitations of treating a subject suffering from cognitive impairment via administering a medicament and BBB manipulator comprising DHA.
It would have been obvious to combine the teachings of Ghosh and Guo because both technologies are drawn to medicaments that penetrate the BBB. While Ghosh teaches the peptoid of their invention is effective in penetrating the BBB on its own, Guo teaches the addition of DHA enhances the solubility of drugs to cross the BBB, further enhancing drug concentrations in the brain, which is a requirement for treating neurological conditions. One of skill in the art would have had a reasonable expectation of success because the structure of darunavir includes peptoid-like residues (e.g. N-benzyl and N-Leu) and its enhanced permeability into the brain was demonstrated to treat neurological conditions that resulted from HIV penetrating the BBB.
claim 8-9, 32
Regarding claim 8-9, and 32-33, Ghosh does not teach the peptoid consisting of peptoid of H-(Nlys-Nspe-Nspe)4-NH2 or being a salt.
Lee teaches a conjugate of a peptide to a peptoid of H-(Nlys-Nspe-Nspe)4-NH2, wherein the peptide is used as a targeting agent, and the peptoid is used to treat cancer (Fig 1; pg 2850, col 1, para 2). Lee teaches the peptoid is cationic (pg 2851, col 2’ para 2), thus satisfying the limitation of the peptoid being a salt.
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Because cancer can occur in the brain resulting in neurological deficiencies, this satisfies the limitation of treating a subject with “mild cognitive impairment”. See 112(b) rejection of claim 1 regarding interpretations of “mild cognitive impairment.”
Bezprozvanny teaches an exemplary peptoid of the structure below (pg 103) as being effective in treating Alzheimer’s disease (abstract).
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Bezprozvanny teaches that peptoids of the formula below may be in the form of a pharmaceutically acceptable salt thereof (pg 3, para 0007).
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It would have been obvious to combine the teachings of Ghosh, Lee, and Bezprozvanny because (1) Ghosh and Bezprozvanny teach poly-peptoids known to treat Alzheimer’s disease are effective in salt form; and (2) Lee teaches the peptoid of H-(Nlys-Nspe-Nspe)4-NH2 being useful for treating cancer. Because both Alzheimer’s disease and cancer can result in “mild cognitive impairment”, one of skill in the art would have had a reasonable expectation of success of using any of these poly-peptoid species as a salt for the treatment of “mild cognitive impairment.”
claim 19-21, 25, 30, 33
Regarding claims 8, 19-21, 25, 30, and 33, Ghosh does not teach any of the peptoid residues are halogenated.
Molchanova teaches the introduction of a chlorine or bromine to a peptoid residue within in a peptoid structure, enhanced its antimicrobial activity via enhancing its hydrophobicity (pg 7, para 4). Molchanova teaches introduction of halogens into a well-known antimicrobial peptoid called “Peptoid 1” shown below (Fig 4).
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Molchanova teaches halogenation at the 4-position of the Nspe residues of Peptoid 1 using either chlorine or bromine (compounds 38 and 44), exhibited enhanced antimicrobial activity and enhanced hydrophobicity over the unmodified Peptoid 1 (pg 3, para 1; Table 2). Molchanova teaches increasing the hydrophobicity of the peptoids enhances hydrophobic interactions making them more effective in killing Gram-negative bacteria (pg 3, para 3). This satisfies the limitation of adding a bromine on an aryl substituent because the Nspe residues of Peptoid 1 were substituted as such. Molchanova’s compounds 38 and 44 satisfy the limitation wherein not all of the aryl moieties comprise a halogen and wherein at least two residues contain a halogen. This also satisfies the limitations of claim 33 that appear to be drawn to peptoid fragments of the poly-peptoid, including H-(Nlys-Nspe-Nspe(p- Br))2-NH2 (satisfied by compound 45), which is included in the last three peptoid residues of compound 38 shown above. See the 112(b) rejection of claim 33 regarding interpretations of this claim. Because microbial infections can lead someone to suffer “mild cognitive impairment” this satisfies a method of treating “mild cognitive impairment” via releasing the person from the cognitive distraction/loss-of-focus as a result of the microbial infection.
Gentry teaches para-bromo and para-chloro halogen additions significantly enhanced in vitro blood-brain barrier permeability, providing evidence for improved delivery to the central nervous system in pharmaceuticals (abstract). More specifically, Gentry teaches modifying an enkephalin peptide analogue, DPLPE-Phe, shown below (pg 1234, Table 1).
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Gentry teaches the halogenation of these peptides increased their lipophilicity, which promoted peptide passage across the BBB (pg 1236, col 2, para 1).
It would have been obvious to combine the teachings of Ghosh, Molchanov, and Gentry because (1) Ghosh teaches peptoids are useful in treating Alzheimer’s disease; (2) Molchanov teaches peptoids of the particular structure are useful in treating bacterial infections; and (3) Gentry teaches halogenation of peptoids and peptides increases their ability to penetrate the BBB. One of skill in the art would have had a reasonable expectation of success because in order for a drug to elicit a stronger response in the brain, it must penetrate the BBB and gentry teaches this can be performed by para-bromination. Molchanov expands on this by specifying which residues result in enhanced hydrophobicity, which is the mechanism by which the peptoids are able to cross the BBB more readily. Ghosh further adds an exemplary peptoid known to treat Alzheimer’s disease which is able to cross the BBB, wherein Molchanov is able to enhance its BBB permeability via adding chlorine or bromine to the residues.
Relevant Prior Art
Young (doi: 10.3390/molecules23020296) teaches several poly-peptoids (shown below) that are useful in treating Alzheimer’s via chelation of metals (Cu, Zn, Fe) and the inhibition of Aβ-aggregation.
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Zhao (doi: 10.1002/smll.201602857) teaches A1P1-Cys as a treatment for Alzheimer’s disease (Fig 1).
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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, Jeffrey Stucker can be reached on 571-272-0911. 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.
/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675
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