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 .
Response to Arguments
Applicant’s arguments, filed 11/20/2025, with respect to the rejection(s) of claim(s) 4-8 and 10-24 under 35 U.S.C. 112(b) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made below.
Claim Status
Claims 1-25 are pending. Claims 1-3 and 9 are withdrawn as non-elected inventions. Claim 25 is new. Claims 1, 3, 4, 6, 8, 10, 11, 12, and 21 are currently amended. Claims 5, 7, 9, 13-20, and 22-24 were previously presented.
Priority
The application is the 371 national stage filing of PCT/HU2020/050023, filed 6/8/2020, which claims priority to HUP1900205, filed 6/7/2019. The filing date of 6/7/2019 is acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
See Abstract; Pg 3, line 14; Pg 17, line 6; Pg 16, lines 11 and 16; Pg 17, line 6; Pg 23, lines 3, 6, 27, and 29; and Pg 24, line 5.
Specification
The disclosure is objected to because of the following informalities (misspellings):
“accomodating” Pg 2, line 34
“unprecendented” Pg 3, line 6
“particularly” Pg 7, line 15
“perfomed” Pg 9, line 11
“ambundant” and “eucaryotic” Pg 10, line 15
“and and” Pg 14, line 15
Appropriate correction is required.
The use of the terms NeutrAvidin (see Figure legends, Pg 13, Pg 16, Pg 19-20, Pg 23-24), LysoTracker (Pg 9, line 17; Pg 20, line 15), and Tentagel (Pg 17, line 18; Pg 18, line 14; Pg 19, line 15), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 7 is objected to because of the following informalities: It is missing a period at the end of the claim. Appropriate correction is required.
Claim Interpretation
Claim 4 recites said peptide of the conjugate “as an endocytosis routing sequence peptide (ERS)”. This limitation describes a functional rather than a structural element of the instant invention. As such, the claim is being interpreted based upon the structural limitation (a peptide of general formula R1-R2-Lys-R3-Trp), where the ERS function is endowed by the structure. This same interpretation is being applied to claims dependent on claim 4 as well as dependent claims that recite “the ERS peptide” or similar language.
Claim Rejections - 35 USC § 112
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 4-8 and 10-24 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 4 recites a cargo “having a size suitable for delivery into a cell via ganglioside binding triggering lipid-raft mediated endocytosis”. The scope of this claim is indefinite as the upper and lower limitations on the size of the cargo is unclear.
By virtue of their dependency on claim 4, claims 5-8 and 10-24 are hereby also rejected for this same reasoning. Although claims 10, 17, 18, 20, and 21 further specify the identity of the cargo (i.e., a “therapeutically active molecule” as recited in claim 10 or “a peptide or a protein” as recited in claim 18), the claims also do not specify any size limitations.
For purposes of examination, the claim is being interpreted as any molecular cargo, regardless of size limitations.
Claim Rejections - 35 USC § 103
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 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.
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.
Rejection for a peptide with the general formula R1-R2-Lys-R3-Trp
Claim(s) 4-8 and 10-25 are rejected under 35 U.S.C. 103 as being unpatentable over Hancock et al. (US8343475B2, published 1/1/2013) in view of Eckert et al. (WO 2010/091294 A2, published 8/12/2010).
Hancock teaches antimicrobial and immunomodulatory polypeptides, such as SEQ ID NO: 639 which comprises the instant SEQ ID NO: 4 and meets the general formula R1-R2-Lys-R3-Trp as recited in the instant claim 1 (Abstract, Table 2A). Hancock teaches that SEQ ID NO: 639 can inhibit the growth of bacterial cells (AMP) ([0009]).
Hancock does not teach generating a conjugate of the instant SEQ ID NO: 4 comprising a cargo and a linker moiety between said peptide and cargo.
Eckert teaches targeted antimicrobial compositions and chimeric moieties comprising a targeting peptide/AMP that targets a bacterial strain or species (Abstract). Chimeric moieties comprise a targeting moiety, which can be an AMP, and an effector, wherein the effector comprises a moiety selected from the group consisting of a detectable label, an AMP, an antibiotic and a photosensitizer ([0007]). The targeting moiety can be chemically conjugated to the effector via a linker comprising PEG or a peptide linker ([0008]). The chimeric moieties can be used in methods to inhibit the growth/proliferation of microorganisms and their biofilms ([0012]). Eckert teaches that AMPs can be attached to one or more targeting moieties and/or effectors, thereby creating a multiple effector composition/strategy ([0139]).
The chimeric moieties can preferentially or specifically deliver the effector to a target microorganism, population of microorganisms, microbial film, a biofilm, or the like ([0059]). The AMPs can be used to inhibit the growth/proliferation of a microorganism and/or to inhibit the formation/growth of a biofilm comprising the microorganism; they can be used alone or in conjunction with other agents (e.g., antibacterial agents) ([0060]).
Thus, regarding claim 4, Hancock teaches an AMP comprising the instant SEQ ID NO: 4 and meeting the general formula of claim 1. Eckert teaches creating chimeric moieties comprising a targeting moiety, such as an AMP, conjugated by a linker to another effector, such as an antibiotic; Ecker further teaches that such chimeric moieties can be used to treat microorganisms and their biofilms by inhibiting their growth/proliferation. Based upon these teachings, it would be prima facie obvious to generate a chimeric moiety or conjugate comprising the AMP of Hancock linked by a linker to an effector (cargo). One skilled in the art would be motivated to do so in order to generate a compound comprising multiple anti-microorganism components, which would create an additive or synergistic impact. One would have a reasonable expectation of success given that Eckert previously established that the combination of an AMP with an effector, such as an antibiotic, could be combined through a linker and successfully treat microorganism and biofilm proliferation/growth.
Additionally, per MPEP 2144.06(I), combining equivalents known for the same purpose is one legal precedent recognized by the courts as directed to common practices that normally require only ordinary skill in the art and are considered routine expedients: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). By extension of this, it would be obvious to combine the antimicrobial peptide of Hancock and an antibiotic taught by Ecker into one compound because both are designed to effectively inhibit/kill microorganisms.
Regarding claims 5, 6, 13, 22, and 23 Eckert teaches the linker/spacer can be a variety of oligopeptide sequences comprised of small apolar amino acids (Pg 160, Table 11). Eckert also teaches that the linker can be PEG of any chain length (Pg 161, Table 11), and the targeting moiety and effector can be conjugated via multiple linking agents ([0192]).
Regarding claims 7 and 11, Hancock teaches the AMP comprising SEQ ID NO: 4.
Regarding claims 8 and 15, Eckert teaches that suitable linking agents include, but are not limited stabilizing groups ([0192]). Eckert further teaches that the linkers can be KKKK or RRRR, which are positively charged (Pg 160, Table 11).
Regarding claim 12, Eckert does not explicitly teach that the linker is coupled to the N-terminus of the peptide. However, Eckert does teach that there are many procedures and linker molecules for attachment of various molecules to peptides or proteins that are known ([0200]). Moreover, one skilled in the art would recognize that attaching a peptide and a cargo moiety to each other via a linker could only be achieved in two different ways. Therefore, it would be obvious to attach the linker to the N-terminus of the peptide.
Regarding claim 14, Eckert teaches several peptides comprising the oligopeptide GG (Pg 160, Table 11).
Regarding claim 16, Eckert teaches that one of the targeting moieties can be penetratin (Pg 53, Table 4). Although penetratin is not explicitly taught as a linker in the chimeric moiety, Ecker further acknowledges that some linkers may be selected to influence some property of the molecule, such as folding, net charge, or hydrophobicity ([0207]). Additionally, Eckert teaches that the purpose of the targeting moieties of Table 4 is to preferentially/specifically bind a microorganism to help deliver effectors to targets ([0081]). Therefore, it would be prima facie obvious to use penetratin as a linker in the conjugate.
Regarding claims 17, 18, 20, and 21 Eckert teaches that effectors can include but are not limited to detectable labels, small molecule antibiotics, AMPs, porphyrins or other photosensitizers, epitope tags/antibodies, microparticles and/or microcapsules, nanoparticles and/or nanocapsules, “carrier” vehicles such as lipids, liposomes, dendrimers, cholic acid-based peptide mimics or other peptide mimics, steroid antibodies, and the like ([0114]).
Regarding claims 19 and 24, Eckert teaches that the linking agent of the linker can comprise a chelator ([0196]). Per the instant specification, a ligand-receptor interaction as understood comprises a binding molecule or receptor and a ligand which is bound by said binding molecule with a high affinity sufficiently strong to provide that the cargo, or a sufficiently high ration thereof, is not dissociated from the ERS-peptide (or linker plus ERS-peptide) part upon routing into the cell (Pg 13, lines 3-6).
Regarding claim 25, Eckert teaches that detectable labels are useful for detecting the presence and/or quantity and/or location of the microorganisms to which the targeting moiety is directed ([0115]). Fluorescent dyes are contemplated (i.e., fluorescein, Texas red, rhodamine, green fluorescent protein and the like) ([0116]).
Rejection for a peptide consisting of the formula R1-R2-Lys-R3-Trp
Claim(s) 4, 7, 10, 11, 17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over André et al. (Identification of peptide ligands for malignancy- and growth-regulating galectins using random phage-display and designed combinatorial peptide libraries. Bioorg Med Chem. 2005 Jan 17;13(2):563-73.) in view of Dings et al. (Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjug Chem. 2010 Jan;21(1):20-7.).
André teaches that members of the galectin family are involved in tumor growth regulation and in establishing characteristics of the malignant phenotype via protein-carbohydrate and protein-protein interactions (Abstract). The interaction of galectin-1 (Gal-1) with the oncogenic H-Ras facilitates the transforming protein’s routing and ensuing cell activation. André teaches the peptide WYKYW (instant SEQ ID NO: 4) binds to galectin-1 (Figures 2 and 3; Pg 567, right column, second paragraph).
André does not teach creating a conjugate comprising a cargo and a linker moiety between the instant SEQ ID NO: 4 and the cargo.
Dings teaches the creation of a conjugate consisting of the cytotoxic agent 6-hydroxypropylacylfulvene (HPAF) and anginex, a peptide that targets Gal-1, which is highly expressed and upregulated in tumor-activated endothelial cells and connected to several types of cancers (Abstract; Introduction, second paragraph). HPAF and anginex are connected through a leucyl ester linkage, providing space between the components, as shown in Figure 1. Dings teaches that the HPAF-anginex conjugate displays better inhibition of tumor growth in cancer mouse models than either individual component alone (Abstract; Figure 2-5).
Therefore, regarding claim 4, André teaches the instant SEQ ID NO: 4 can bind to Gal-1. Dings teaches a peptide-therapeutic conjugate consisting of a cytotoxic agent linked to the peptide anginex that can bind Gal-1, which is highly expressed on endothelial cells of cancerous tumors. Based on these teachings, it would be obvious to substitute anginex for the instant SEQ ID NO: 4. One skilled in the art would be motivated to do so as the art teaches that SEQ ID NO: 4 can bind to Gal-1. One would have a reasonable expectation of success as Dings already established that such a conjugate could be used to successfully target Gal-1 expressing endothelial cells.
Regarding claims 7 and 11, André teaches the instant SEQ ID NO: 4.
Regarding claim 10 17, 21, as described above, Dings teaches the therapeutically active molecule HPAF.
Claim(s) 4, 7, 10, 11, 17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over André et al. (Identification of peptide ligands for malignancy- and growth-regulating galectins using random phage-display and designed combinatorial peptide libraries. Bioorg Med Chem. 2005 Jan 17;13(2):563-73.) and Dings et al. (Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjug Chem. 2010 Jan;21(1):20-7.) in view of Kant (Homo-β-amino acid containing MBP(85–99) analogs alleviate experimental autoimmune encephalomyelitis. Sci Rep 5, 8205 (2015).) as evidenced by Nosov (“Amino Acids”, March 16, 2016, accessed 2/24/2026).
The teachings of André and Dings have been set forth above. André further teaches that, in the search to identify peptides that bind Gal-1 that led to the peptide WYKYW, the Tyr residues were kept constant (equivalent to R2 and R3 in the instant general formula R1-R2-Lys-R3-Trp; Figure 1; Pg 565, right column, middle of first paragraph); additionally, changing Lys to and/or Trp at the C-terminal position to Asp substantially reduced the peptide’s ability to bind to Gal-1 (Figure 2 and 3). André and Dings do not teach a peptide with the general formula R1-R2-Lys-R3-Trp wherein R1, R2, and R3 are homo-β-amino acids of Trp, Tyr, and Tyr, respectively.
Kant teaches improvements to the peptide inhibitor J5, wherein amino acid residues are substituted for homo-β-amino acids (Abstract). Kant teaches that homo-β-amino acids have their amino group attached to β-carbon instead of an α-carbon and their side chains (R groups) are identical to that of their naturally occurring counterparts (Pg 2, left column, third paragraph). Introducing homo-β-amino acids into J5 improved its resistance to proteases and increased peptide backbone flexibility and ability to cross cell barriers (Pg 6, “Discussion”, left column, second paragraph, and Pg 8, left column, third paragraph). Nosov discloses homo-β-amino acids of Trp and Tyr.
Therefore, regarding claim 11, André and Dings teach a peptide consisting of “WYKYW” conjugated to a molecular cargo through a linker, wherein modification of the Lys and C-terminal Trp results in reduced ability to bind Gal-1. Kant teaches that introduction of homo-β-amino acids into a peptide improves its protease resistance, peptide backbone flexibility, and ability to cross cell barriers; Nosov evidences homo-β-amino acids of Trp and Tyr. Based upon these teachings, it would be prima facie obvious to substitute Trp and Tyr at positions R1, R2, and R3 for their homo-β-amino acid counterparts, thus leading to the instant SEQ ID NO: 15, 16, 18, 20, 22, and 23. One skilled in the art would have been motivated to do so in order to confer the advantages taught by Kant into the peptide conjugate of André and Dings. One would have a reasonable expectation of success as Kant successfully improved other peptides through substituting their L-amino acids for homo-β-amino acids.
Additionally, it would be obvious to try substituting each of the residues Trp and Tyr residues at positions R1, R2, and R3 in the peptide “WYKYW” for their corresponding homo-β-amino acids. At the time of filing, the art recognized that substitution of α-amino acids for their corresponding homo-β-amino acids in peptide sequences improved the peptide in various ways described above. One of ordinary skill in the art would recognize, based upon the teachings of André and Dings, only the amino acids at positions R1, R2, and R3 were ideal substitutions as alterations to the Lys and C-terminal Trp negatively impact the protein’s ability to bind to Gal-1; this would leave only three potential residues that could be substituted. Therefore, it would be obvious to try each possible combination of substituting R1, R2, and R3 for their corresponding homo-β-amino acids based upon the teachings of André and Dings, thus leading one to the instant SEQ ID NO: 15, 16, 18, 20, 22, and 23.
Claim(s) 4-8, 10-15, 17, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over André et al. (Identification of peptide ligands for malignancy- and growth-regulating galectins using random phage-display and designed combinatorial peptide libraries. Bioorg Med Chem. 2005 Jan 17;13(2):563-73.) and Dings et al. (Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjug Chem. 2010 Jan;21(1):20-7.), as applied to claims 4, 7, 10, 11, 17, and 21 above, and further in view of Chen et al. (Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev. 2013 Oct;65(10):1357-69.).
The teachings of André and Dings have been set forth above. André and Dings do not teach connecting the instant SEQ ID NO: 4 to a cargo via a spacer oligopeptide sequence or a PEG-based oligomeric moiety.
Chen teaches peptide linkers used to connect fusion proteins or distinct protein domains together (Abstract). Chen teaches that connecting components without a flexible linker may lead to undesirable outcomes such as misfolding of the protein, low production yield, or impaired bioactivity (Pg 2, “Introduction”, second paragraph). Peptide linkers can adopt various structures and exert diverse functions. In particular, flexible linkers allow joined domains a certain degree of movement or interaction and are composed of small non-polar or polar amino acids, which contributes to the flexibility and mobility of the connected domains (Pg 4, “3.1 Flexible linkers”; Table 4).
Thus, regarding claims 5, 6, and 13, André and Dings teach a conjugate comprising the instant SEQ ID NO: 4 connected to a cargo via a leucyl ester linkage. Chen teaches peptide linkers can connect distinct domains or pieces of conjugates together, including the advantages of using flexible linkers and the disadvantages associated with the lack of a linker completely. Based on these teachings, it would be prima facie obvious to substitute the leucyl ester linker taught by André and Dings for a flexible peptide linker taught by Chen. One skilled in the art would be motivated to do so in order to take of advantage of the benefits of a flexible linker as taught by Chen. One would have a reasonable expectation of success given that Chen established that such linkers are commonly used in the art to connect peptide parts.
Regarding claims 8 and 15, Chen teaches that naturally-occurring peptide linkers preferably include charged residues (Pg 3, second paragraph).
Regarding claim 12, Chen teaches examples wherein the peptide linker is attached to the N-terminus of another peptide sequence (Pg 5, “3.1 Flexible linkers”, third paragraph).
Regarding claim 14, 22, and 23, Chen teaches linkers comprising GG (Pg 5, “3.1 Flexible linkers,” second and 4th paragraphs; Tables 2 and 3).
Claim(s) 4-8 and 10-25 are rejected under 35 U.S.C. 103 as being unpatentable over André et al. (Identification of peptide ligands for malignancy- and growth-regulating galectins using random phage-display and designed combinatorial peptide libraries. Bioorg Med Chem. 2005 Jan 17;13(2):563-73.), Dings et al. (Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjug Chem. 2010 Jan;21(1):20-7.), and Chen et al. (Chen X, Zaro JL, Shen WC. Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev. 2013 Oct;65(10):1357-69.), as applied to claims 4-8, 10-15, 17, and 21-23 above, and further in view of Eckert et al. (WO 2010/091294 A2, published 8/12/2010).
The teachings of André, Dings, and Chen have been set forth above. André, Dings, and Chen do not teach that the peptide linker is a penetratin moiety.
As stated above, Eckert teaches chimeric moieties comprising targeting moiety and an effector, wherein the effector comprises a moiety selected from the group consisting of a detectable label, an AMP, an antibiotic and a photosensitizer ([0007]). The targeting moiety can be chemically conjugated to the effector via a linker comprising PEG or a peptide linker ([0008]).
Eckert teaches that one of the targeting moieties can be the cell penetrating peptide penetratin (Pg 53, Table 4). Although penetratin is not explicitly taught as a linker in the chimeric moiety, Ecker states that some linkers may be selected to influence some property of the molecule, such as folding, net charge, or hydrophobicity ([0207]). Additionally, Eckert teaches that the purpose of the targeting moieties of Table 4 is to preferentially/specifically bind to a desired target to help deliver effectors to targets ([0081]).
Thus, regarding claim 16, André, Dings, and Chen teach a conjugate consisting of SEQ ID NO: 4 linked via a peptide linker to a cargo molecule. Eckert teaches the cell penetrating peptide penetratin can be included in chimieric moieties and that peptide linkers can be selected to influence some property of the molecule. Therefore, it would be prima facie obvious to use penetratin as the peptide linker in the conjugate. One would be motivated to do so in order to take advantage of the benefits of including penetratin in the conjugate, namely, the addition of another feature that would help get cargo into the cells targeted by SEQ ID NO: 4. One would have a reasonable expectation of success as Eckert established that penetratin could be included in such conjugates.
Regarding claims 18 and 20, Eckert teaches that effectors can include but are not limited to detectable labels, small molecule antibiotics, AMPs, porphyrins or other photosensitizers, epitope tags/antibodies, microparticles and/or microcapsules, nanoparticles and/or nanocapsules, “carrier” vehicles such as lipids, liposomes, dendrimers, cholic acid-based peptide mimics or other peptide mimics, steroid antibodies, and the like ([0114]).
Regarding claims 19 and 24, Eckert teaches that the linking agent of the linker can comprise a chelator ([0196]). Per the instant specification, a ligand-receptor interaction as understood comprises a binding molecule or receptor and a ligand which is bound by said binding molecule with a high affinity sufficiently strong to provide that the cargo, or a sufficiently high ration thereof, is not dissociated from the ERS-peptide (or linker plus ERS-peptide) part upon routing into the cell (Pg 13, lines 3-6).
Regarding claim 25, Eckert teaches that detectable labels are useful for detecting the presence and/or quantity and/or location of the microorganisms to which the targeting moiety is directed ([0115]). Fluorescent dyes are contemplated (i.e., fluorescein, Texas red, rhodamine, green fluorescent protein and the like) ([0116]).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara E Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658