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 .
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 5/28/26 are acknowledged. Any objection or rejection from the 1/28/26 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and the species of the hexamer polypeptide of beta (B6; see first structure of figure 11) and sulforaphane were elected.
As discussed below, the amended claims are unclear and it is not clear if the hexamer polypeptide of beta (B6) reads on instant claim 1. For purposes of examination, claim 1 has been interpreted as included the elected species.
The combination of elected species was found to be free of the prior art in the context of the instant claims. No claims are drawn solely to the combination of elected species. The search was expanded in accord with MPEP 803.02.
Claims 17-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/19/25.
As recognized in the response of 11/19/25 claim 9 does not read on the elected species (the elected species contains substituted beta-alanine not gamma-alanine).
Claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/19/25.
Claims 1-8 and 10-16 are being examined.
Priority
The priority information is found in the filing receipt of 6/30/23.
Specification
The disclosure is objected to because of the following informalities:
The proposed specification amendment of 5/28/26 attempts to delete a word on page 10 line 7. MPEP 2163.07 recognizes that amendments can be made to correct an obvious error where one skilled in the art would not only recognize the existence of an error but also the appropriate correction. In the instant case, the proposed amendment of 5/28/26 that attempts to delete a word on page 10 line 7 does not appear to be made to correct an obvious error where one skilled in the art would not only recognize the existence of an error but also the appropriate correction. As such, the amendment to the specification filed 5/28/26 is objected to under 35 USC 132 (a).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claims were previously rejected under 35 USC 112(b)/2nd. Since claim 1 has been amended, updated and or new rejections appear below.
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 1-8 and 10-16 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 as amended recites ‘substituted methylene groups CR2 having a formula of HN(R3)(CRi1CRi2)nC(=O)OH, wherein n is an integer greater than equal to 2, i is an index’. First, the claim language ‘an integer greater than equal to 2’ is unclear. It is unclear if such language is the same as ‘an integer greater than or equal to 2’. The Ri2 variable is not further described and it is unclear if it can be anything. It is unclear if the elected species is intended to read on the claim. Figure 11 shows the elected species which includes a beta-amino acid (figure 5 also shows an example of a beta amino acid). If the intent is such that n can be 2, then the formula would be HN(R3)(CRi1CRi2CRi1CRi2)C(=O)OH. However, beta-amino acids only include 2 carbons (not 4) in between the amino and carboxyl termini. It is not clear if claims 7-8 are proper dependent claims. Further, claim 1 lines 4-5 refer to ‘optionally substituted methylene groups’ and then go on to refer to ‘substituted methylene groups’ (claim 1 line 6). It is not clear if substitution is optional or required. Further, it is unclear if substitution is in relation to the formula or if the formula is the substituted group. None of the dependent claims clarify the claim scope.
The fifth to last line of claim 1 as amended recites ‘R3 , Ri1 and Ri1’. It is unclear why Ri1 is recited twice. It is unclear if different Ri1 are required or if there is some type of typographical error. None of the dependent claims clarify the claim scope.
The third to last line of claim 1 as amended recites ‘alkylheteroaryl alkylamino’ as options for some of the variable groups. The scope of an ‘alkylheteroaryl alkylamino’ is unclear. It is unclear if features or both an alkylheteroaryl and an alkylamino are required or if the intent is that they are separate options. None of the dependent claims clarify the claim scope.
As amended, the last line of claim 1 recites ‘either Rj1 ….’. However, the claim does not previously recite Rj1. There is insufficient antecedent basis for this limitation in the claim. As such, the scope of the claim is unclear and it is unclear which components can form a carbocycle. None of the dependent claims clarify the claim scope.
Claim 1 lines 2-3 recites ‘linear chain’. Claim 6 lines 1-2 recite ‘linear chain’. Claim 11 recites linear chain, Claim 15 lines 2-3 recite ‘linear chain’. Pages 9-10 connecting paragraph and the first complete paragraph of page 10 of the original specification define and describe what is meant by linear. Linear is described as not having any cyclic or aryl structures (page 9 lines 28-29) and then an example of a linear agent is for example thiotepa (page 10 line 7 of the original specification). Piccariello et al. (US 2004/0063628) teach the structure of thiotepa as including 3 3-membered rings (section 2381 on page 167). As such, contradictory information is provided about the meaning of linear. Linear is described as not having any cyclic structure, yet an example of a linear agent includes 3 cyclic structures. Thus, it is unclear what is intended to be within the scope of the claim. Further, instant claim 10 refers to ‘saccharide moieties’. It is unclear if claim 10 is a proper dependent claim since a saccharide would seem to contain a cyclic structure. It is not clear what substitutions or side chain groups are acceptable for the oligomer or agent to be within the scope of ‘linear’. None of the dependent claims clarify the claim scope.
Claim 10 refers to ‘steric groups’. It is unclear how to determine whether or not a group is a steric group. The term “steric groups” in claim 10 is a relative term which renders the claim indefinite. The term “steric groups” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how to determine whether or not a group is a steric group.
Claim 11 recites ‘between 4-8 nonproteogenic amino acids’. It is unclear if claim 11 is intended to be in reference as to the length or type of amino acid. It is unclear if claim 11 is setting forth a minimum length of the oligomer or a maximum length of the peptide or is referring to the types of amino acids. The elected species has been interpreted as reading on claim 11.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
Response to Arguments – 112(b)/2nd
Applicant's arguments filed 5/28/26 have been fully considered but they are not persuasive.
Although applicants argue about a linear chain and a linear agent, claim 1 expressly recites linear chain in the context of the peptidic oligomer and claim 6 recites a linear chain in the context of the agent. Since the word ‘linear’ is used in the claims, in order to interpret the claim the scope of linear should be clear. Pages 9-10 connecting paragraph and the first complete paragraph of page 10 of the original specification define and describe what is meant by linear. Linear is described as not having any cyclic or aryl structures (page 9 lines 28-29) and then an example of a linear agent is for example thiotepa (page 10 line 7 of the original specification). Piccariello et al. (US 2004/0063628) teach the structure of thiotepa as including 3 3-membered rings (section 2381 on page 167). As such, contradictory information is provided about the meaning of linear. Linear is described as not having any cyclic structure, yet an example of a linear agent includes 3 cyclic structures. Thus, it is unclear what is intended to be within the scope of the claim.
Although applicants argue that one would recognize the scope of steric based on examples, exemplification is not a definition.
Although applicants argue that steric is established in terms of bulk and hindering, such terms are subjective.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Claims were previously rejected under 35 USC 112(a)/1st. Since claim 1 has been amended, an update rejection appears below.
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 1-8 and 10-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
(1) Scope of the invention/Partial structure/disclosure of drawings:
As set forth above, the claims are unclear for many reasons. The claims have been given the broadest reasonable interpretation.
Claim 1 refers to an oligomer and recites ‘two or more optionally substituted methylene groups’ and refers to ‘encapsulating an agent’.
Claim 11 refers to 8 amino acids. There are many possible substituted groups. If one simply considered an 8-mer with any given position substituted to at least any of the 20 standard amino acids, there are at least 208 (i.e. 25600000000) different possible sequences. Further, there are many other possible combinations of substitutions. There are at least 4 locations for substitutions for beta-alanine. There are at least 6 locations for substitutions for gamma-alanine. As such, the genus is large. With respect to the agent, the specification describes the agent broadly (page 9 of the specification). The agent is not limited to a specific size.
None of the dependent claims limit both the peptidic oligomer and agent to specific compounds.
The examples (see figure 11) appear to relate to 2 peptidic oligomers and a single agent (sulforaphane; see figure 17).
(2) Level of skill and knowledge in the art/predictability in the art:
The level of skill in the art is high.
Claim 1 refers to an oligomer and recites ‘two or more optionally substituted methylene groups’ and refers to ‘encapsulating an agent’. Since the claims requires the agent to be encapsulated, the peptidic oligomer must be able to perform such function.
Goel et al. (‘Self-assembly of beta-alanine homotetramer: formation of nanovesicles for drug delivery’ Journal of Materials Chemistry B v3 2015 pages 5849-5857; ‘Goel’) recognizes that beta-amino acids can form sheets, turns and aggregates and many structural variations are possible (page 5849 paragraph connecting columns 1-2). Goel teach that beta-peptide assembly has largely been theoretical and fabrication ‘in a controlled fashion is an area that is largely unexplored’ (page 5849 paragraph connecting columns 1-2). One would not necessarily recognize sheets, turns and aggregates as being capable of encapsulating an agent. One would not recognize a largely unexplored area as having an adequate structure function relationship to describe which structures would have the recited function.
(3) Physical and/or chemical properties and (4) Functional characteristics:
Claim 1 refers to an oligomer and recites ‘two or more optionally substituted methylene groups’ and refers to ‘encapsulating an agent’. Since the claims requires the agent to be encapsulated, the peptidic oligomer must be able to perform such function for a wide range of possible agents.
There is no adequate disclosed correlation between structure and function particularly related to what structures are adequate to result in the function of encapsulating as recited in the claim, specifically for the many possible substitutions and structures possible. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus and that there is a lack of the predictability in the art thus that the applicant was not in possession of the claimed genus.
(5) Method of making the claimed invention/actual reduction to practice:
The examples (see figure 11) appear to relate to 2 peptidic oligomers and a single agent (sulforaphane; see figure 17). It is unclear if the elected species and examples of figure 11 are intended to read on the claim. Figure 11 shows the elected species which includes a beta-amino acid (figure 5 also shows an example of a beta amino acid). If the intent is such that n can be 2, then the formula would be HN(R3)(CRi1CRi2CRi1CRi2)C(=O)OH. However, beta-amino acids only include 2 carbons (not 4) in between the amino and carboxyl termini. It is not clear if claims 7-8 are proper dependent claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments – 112(a)/1st
Applicant's arguments filed 5/28/26 have been fully considered but they are not persuasive.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Claim Rejections - 35 USC § 102
Claims were previously rejected under 102 based on the reference cited below. Since claim 1 has been amended, the rejection is updated to correspond to the instant claims.
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.
Claim(s) 1-4, 6-8, 10-13 and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guichard et al. (US 2018/0244718; ‘Guichard’).
Guichard teach foldamer helix bundle-based molecular encapsulation via oligomeric compounds (title and abstract). Guichard specifically teach oligourea H1 (figure 1B and claim 1). Guichard teach that ‘u’ denotes urea based residue where figure 1a discloses the oligourea based sequence. Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069, 0279 and 0293 and figure 36).
In relation to the peptidic oligomer of claims 1, 6-8 and 10-12, Guichard specifically teach oligourea H1 (figure 1B). Guichard teach that ‘u’ denotes urea based residue where figure 1a discloses the oligourea based sequence. As shown in figure 1a, the oligourea sequence of each unit comprises -NH-CH(R)-CH2- where R is the amino acid side chain group. H1 comprise at least 2 substituted methylene groups (i.e. -CH(R)-CH2-) which correspond to substituted beta-alanine. Further, the residues are connected by amide bonds. With respect to amino and carboxylic acid groups, the Glu residue contains a terminal carboxylic acid group and the Lys residues contain terminal amino groups. Further, peptides are written from N-terminal to C-terminal end (see figure 1b). The amino acid side chains of oligourea H1 are interpreted to be steric groups as in claim 10. Oligourea H1 is made of 5 different nonproteogenic amino acids as in claim 11 as currently interpreted. In relation to claim 12, the compounds are described as therapeutic (claim 27).
In relation to the encapsulated agent of claims 1-4, 6 and 15, Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069 and 0279 and figure 36). In relation to claim 4, isopropanol is a known antiseptic. In relation to claim 6, isopropanol is of structure (CH3)2-CH-OH.
In relation to claim 13, Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069, 0279 and 0293 and figure 36).
As set forth above, the claims are unclear for many reasons. The claims have been given the broadest reasonable interpretation and the prior art cited above has been interpreted as reading on the claims as set forth above.
Response to Arguments - 102
Applicant's arguments filed 5/28/26 have been fully considered but they are not persuasive.
Although applicants argue about differences in structurally features, as set forth above in the 112(b)/2nd rejection the claims are unclear for many reasons and the required structural features are unclear for many reasons.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 103 based on the references cited below. Since claim 1 has been amended, the rejections are updated to correspond to the instant claims.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-8 and 10-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Guichard et al. (US 2018/0244718; ‘Guichard’) in view of Dagan et al. (US 7,879,822; cited with IDS 11/5/24; ‘Dagan’).
Guichard teach foldamer helix bundle-based molecular encapsulation via oligomeric compounds (title and abstract). Guichard specifically teach oligourea H1 (figure 1B and claim 1). Guichard teach that ‘u’ denotes urea based residue where figure 1a discloses that the oligourea based sequence. Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069, 0279 and 0293 and figure 36). Guichard specifically teach the inclusion of an anti-cancer agent (section 0154).
Guichard does not teach the inclusion of sulforaphane.
Dagan teach that sulforaphane is a known anticancer agent (column 1 lines 30-31).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Guichard based on the specific teachings and suggestions of Guichard. Guichard specifically teach the inclusion of an anti-cancer agent (section 0154) so one would have been motivated to include the known anticancer agent sulforaphane as taught by Dagan (column 1 lines 30-31). Since Guichard teach for therapeutic applications (claim 27) one would have been motivated to optimize the amount of the agent. One would have had a reasonable expectation of success since the components and methods of making were known.
In relation to the peptidic oligomer of claims 1, 6-8 and 10-12, Guichard specifically teach oligourea H1 (figure 1B). Guichard teach that ‘u’ denotes urea based residue where figure 1a discloses the oligourea based sequence. As shown in figure 1a, the oligourea sequence of each unit comprises -NH-CH(R)-CH2- where R is the amino acid side chain group. H1 comprises at least 2 substituted methylene groups (i.e. -CH(R)-CH2-) which correspond to substituted beta-alanine. Further, the residues are connected by amide bonds. With respect to amino and carboxylic acid groups, the Glu residue contains a terminal carboxylic acid group and the Lys residues contain terminal amino groups. Further, peptides are written from N-terminal to C-terminal end (see figure 1b). The amino acid side chains of oligourea H1 are interpreted to be steric groups as in claim 10. . Oligourea H1 is made of 5 different nonproteogenic amino acids as in claim 11 as currently interpreted. In relation to claim 12, the compounds are described as therapeutic (claim 27).
In relation to the encapsulated agent of claims 1-4, 6 and 15, Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069 and 0279 and figure 36). In relation to claim 4, isopropanol is a known antiseptic. In relation to claim 6, isopropanol is of structure (CH3)2-CH-OH.
In relation to claim 13, Guichard teach oligourea H1 with isopropanol guest molecules within the helical bundle (sections 0069, 0279 and 0293 and figure 36).
In relation to claim 14, since Guichard teach for therapeutic applications (claim 27) one would have been motivated to optimize the amount of the agent.
In relation to claims 5 and 16, Dagan teach that sulforaphane is a known anticancer agent (column 1 lines 30-31).
As set forth above, the claims are unclear for many reasons. The claims have been given the broadest reasonable interpretation and the prior art cited above has been interpreted as suggesting the claim limitations as set forth above.
Claim(s) 1-4, 6-8 and 10-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Goel et al. (‘Self-assembly of beta-alanine homotetramer: formation of nanovesicles for drug delivery’ Journal of Materials Chemistry B v3 2015 pages 5849-5857; ‘Goel’) in view of Gopalan et al. (‘Geometrically precise building blocks: the self-assembly of beta-peptides’ Chemistry & Biology v22 November 19, 2015 pages 1417-1423; ‘Gopalan’).
Goel teach the beta-alanine homotetramer (H2N-BetaAla- BetaAla- BetaAla- BetaAla-CONH2) (abstract). Goel teach that nanovesicles were formed for drug delivery specifically of L-DOPA which is an anti-Parkinson’s drug (abstract). Goel teach that the nanovesicles encapsulate the L-DOPA and the assemblies can be considered as delivery vehicles (abstract). Goel teach a goal of targeting the blood brain barrier (page 5850 first paragraph). Goel teach the specifics of the peptide synthesis and the preparation of the assemblies and drug encapsulation (page 5855).
The peptide of Goel does not contain a carboxylic acid or ester group as recited in claim 1.
Gopalan teach beta-peptides (title and abstract). Gopalan teach the use of beta amino acids specifically those with a terminal carboxylic acid (figures 1 and 3) and recognizes hydrogen bonding (page 1418 first complete paragraph and last complete paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Goel based on the specific teachings and suggestions of Goel. Since Gopalan also teach beta-peptides (title and abstract) and recognizes the inclusion of a terminal carboxylic acid (figures 1 and 3) and recognizes hydrogen bonding as beneficial (page 1418 first complete paragraph and last complete paragraph) one would have been motivated to modify the beta-alanine homotetramer (H2N-BetaAla- BetaAla- BetaAla- BetaAla-CONH2) to include a C-terminal carboxylic acid instead of an amine (H2N-BetaAla- BetaAla- BetaAla- BetaAla-COOH). Further, since Goel teach that nanovesicles were formed for drug delivery specifically of L-DOPA which is an anti-Parkinson’s drug (abstract) and teach a goal of targeting the blood brain barrier (page 5850 first paragraph) one would have been motivated to include targeting moieties for such purpose. One would have had a reasonable expectation of success since the components and methods of making were known.
In relation to the peptidic oligomer of claims 1, 6-8 and 11-12, H2N-BetaAla- BetaAla- BetaAla- BetaAla-COOH as discussed above comprises 4 beta-alanine residues (which each comprise 2 methylene groups) and a terminal amino and carboxylic acid. In relation to claim 10, Goal teach a goal of targeting the blood brain barrier (page 5850 first paragraph) so one would have been motivated to include targeting moieties for such purpose. In relation to claim 12, Goel teach for drug delivery (title and abstract).
In relation to the encapsulated agent of claims 1-4, 6 and 15, Goel teach that nanovesicles were formed for drug delivery specifically of L-DOPA which is an anti-Parkinson’s drug (abstract) which is interpreted as being a linear agent.
In relation to claims 13-14, Goel teach the specifics of the peptide synthesis and the preparation of the assemblies and drug encapsulation (page 5855). Goel teach 3.3 umol of peptide and 3.04 umol L-DOPA (page 5855 section ‘Preparation of drug loaded vesicles’). Further, since Goel teach encapsulation efficiency (page 5855 last complete paragraph) one would have been motivated to optimize the amounts for such purpose.
As set forth above, the claims are unclear for many reasons. The claims have been given the broadest reasonable interpretation and the prior art cited above has been interpreted as suggesting the claim limitations as set forth above.
Claim(s) 1-8 and 10-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Goel et al. (‘Self-assembly of beta-alanine homotetramer: formation of nanovesicles for drug delivery’ Journal of Materials Chemistry B v3 2015 pages 5849-5857) in view of Gopalan et al. (‘Geometrically precise building blocks: the self-assembly of beta-peptides’ Chemistry & Biology v22 November 19, 2015 pages 1417-1423) in view of Williams et al. (‘Expanded alpha helices as encapsulating drug delivery vehicles’ ACS Publications Spring 2021, 1 page).
Goel teach the beta-alanine homotetramer (H2N-BetaAla- BetaAla- BetaAla- BetaAla-CONH2) (abstract). Goel teach that nanovesicles were formed for drug delivery specifically of L-DOPA which is an anti-Parkinson’s drug (abstract). Goel teach that the nanovesicles encapsulate the L-DOPA and the assemblies can be considered as delivery vehicles (abstract). Goel teach a goal of targeting the blood brain barrier (page 5850 first paragraph). Goel teach the specifics of the peptide synthesis and the preparation of the assemblies and drug encapsulation (page 5855). Goel teach a helix type backbone (abstract and figure 4).
Goel does not teach the inclusion of sulforaphane.
Gopalan teach beta-peptides (title and abstract). Gopalan teach the use of beta amino acids specifically those with a terminal carboxylic acid (figures 1 and 3) and recognizes hydrogen bonding (page 1418 first complete paragraph and last complete paragraph).
Williams teach alanine derivatives that fold into an alpha helix for encapsulating sulforaphane (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Goel based on the specific teachings and suggestions of Goel. Since Gopalan also teach beta-peptides (title and abstract) and recognizes the inclusion of a terminal carboxylic acid (figures 1 and 3) and recognizes hydrogen bonding as beneficial (page 1418 first complete paragraph and last complete paragraph) one would have been motivated to modify the beta-alanine homotetramer (H2N-BetaAla- BetaAla- BetaAla- BetaAla-CONH2) to include a C-terminal carboxylic acid instead of an amine (H2N-BetaAla- BetaAla- BetaAla- BetaAla-COOH). Further, since Williams teach alanine derivatives that fold into an alpha helix for encapsulating sulforaphane (abstract) one would have been motivated to use the known encapsulating agent suggested by Goel (and modified by Gopalan) for encapsulating sulforaphane. One would have had a reasonable expectation of success since the components and methods of making were known.
In relation to the peptidic oligomer of claims 1, 6-8 and 11-12, H2N-BetaAla- BetaAla- BetaAla- BetaAla-COOH as discussed above comprises 4 beta-alanine residues (which each comprise 2 methylene groups) and a terminal amino and carboxylic acid. In relation to claim 10, Williams teach sulforaphane as a therapeutic molecule so one would have been motivated to include targeting moieties for such purpose. In relation to claim 12, Goel teach for drug delivery (title and abstract).
In relation to the encapsulated agent of claims 1-6 and 15-16, Williams teach alanine derivatives that fold into an alpha helix for encapsulating sulforaphane (abstract).
In relation to claims 13-14, Goel teach the specifics of the peptide synthesis and the preparation of the assemblies and drug encapsulation (page 5855). Goel teach 3.3 umol of peptide and 3.04 umol drug (page 5855 section ‘Preparation of drug loaded vesicles’). Further, since Goel teach encapsulation efficiency (page 5855 last complete paragraph) one would have been motivated to optimize the amounts for such purpose.
As set forth above, the claims are unclear for many reasons. The claims have been given the broadest reasonable interpretation and the prior art cited above has been interpreted as suggesting the claim limitations as set forth above.
Response to Arguments - 103
Applicant's arguments filed 5/28/26 have been fully considered but they are not persuasive.
Although applicants argue about differences in structurally features, as set forth above in the 112(b)/2nd rejection the claims are unclear for many reasons and the required structural features are unclear for many reasons.
Although applicants argue that it is the vesicular structure not the underlying linear beta-alanine chain that performs encapsulation, instant claim 1 line 1 uses the open ended comprising language thus the claim is open to the inclusion of other components. There is no reasonable basis to conclude that claim 1 excludes vesicles.
Although applicants argue that L-DOPA is not a linear agent, claim 1 merely recites ‘encapsulating an agent’. Linear is described as not having any cyclic or aryl structures (page 9 lines 28-29) and then an example of a linear agent is for example thiotepa (page 10 line 7 of the original specification). Piccariello et al. (US 2004/0063628) teach the structure of thiotepa as including 3 3-membered rings (section 2381 on page 167). As such, contradictory information is provided about the meaning of linear. Linear is described as not having any cyclic structure, yet an example of a linear agent includes 3 cyclic structures. Thus, it is unclear what is intended to be within the scope of the claim.
Although applicants argue about the teachings of Gopalan alone, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants refer to a right to submit a declaration, not declaration is of record.
Although applicants argue about the teachings of Williams alone, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue about claims 2 and 14, such claims are addressed in the rejections set forth above.
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.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
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