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 .
Priority
This application claims the benefit, and is a 35 U.S.C. 371 national state application, of International Patent Application No. PCT/US22/43358 filed on September 13, 2022, which claims the priority benefit of US Provisional Application Number 63/299,746 filed on January 14, 2022.
Status of Claims
Claims 1, 3-8, 12, 13, 16, 18-21, 24-27, 29, 33-38, 40, 41, 44, 45, and 48 are pending.
Claim 48 is new. Claims 1, 3-8, 12, 13, 16, 18-21, 24-27, 29, 33-38, 40, 41, 44, and 45 are currently amended, filed on February 18, 2025.
Claims 1, 3-8, 12, 13, 16, 18-21, 24-27, 29, 33-38, 40, 41, 44, 45, and 48 are currently examined on the merits herein.
Information Disclosure Statement
The IDS filed on 7/13/2024 is being considered.
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 - Amino acid sequence SEQ ID NO: 1 appearing in the specification (see [00071]) and the sequence listing submitted on February 18, 2025, are inconsistent. SEQ ID NO.: 1, AVSEHQLLHDKGKSIQDLRRRELLEKLLxKLHTAEIRATSEVSPNSeeeeeeeeeeeeeeeeeeee (see [00071]) of the instant specification comprises an additional arginine (R) in the underscored part of the sequence compared to the sequence listing of the instantly claimed invention.
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:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Objections
Claims 26, 27, 29, 33, 36, 37, 41, and 45 are objected to because of the following informalities: “amino acid” after the specifically named amino acid , i.e.., glutamic acid and/or aspartic acid, should be deleted to avoid redundancy.
The instant specification states “administration of a compound provided herein (e.g., Ab46-D-Glu20)” (see [00068], [00070], and [000156]). The definition of Ab46 is not provided elsewhere in the instant specification.
The sequence numbers in the specification have an extra (.) (i.e., SEQ ID NO.:). The sequence numbers should be stated as “SEQ ID NO:1” or “SEQ ID NO:2”, etc.
Appropriate corrections are required.
Claim/Sequence Interpretation
Claim 38 recite the compound has at least 75% sequence identity or more to SEQ ID NO: 1, SEQ ID NO: 3, or SEQ IDNO: 4. The claim is given this construction in view of the instant specification which states in some of the embodiments, the compound has at least 75% sequence identity or more (e.g., at least 80% sequence identify or more, at least 85% sequence identify or more, at least 90% sequence identify or more, or at least 95% sequence identify or more) to SEQ ID NO: 1 (see [00026]); in some embodiments, a compound for treating Osteogenesis Imperfecta (OI) in an individual (e.g., in need thereof), is Compound 1 (see [00028]); in some of the embodiments, the compound has at least 75% sequence identity or more (e.g., at least 80% sequence identify or more, at least 85% sequence identify or more, at least 90% sequence identify or more, or at least 95% sequence identify or more) to SEQ ID NO: 3 (see [00030]); in some of the embodiments, the compound has at least 75% sequence identity or more (e.g., at least 80% sequence identify or more, at least 85% sequence identify or more, at least 90% sequence identify or more, or at least 95% sequence identify or more) to SEQ ID NO: 4 (see [00032]). For the purposes of compact prosecution and applying prior art, sequences of the claimed invention are broadly interpreted to encompass (including but not limited to) sequence that are at least 75% sequence identity or more to SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 4.
Claims 1, 34-37, 41, 45, and 48 recite “having a structure X-Y-Z, wherein …. Y is a linker”; “Y is a non-releasable oligopeptide linker”; “Y is a releasable oligopeptide linker”. The instant specification states that in some of the embodiments provided herein, Y is a non-releasable linker (e.g., containing at least one carbon-carbon bond and/or at least one amide bond); in some of the embodiments provided herein, Y is a releasable linker (e.g., containing at least one disulfide (SS), at least one ester (e.g., O(C=0)), and/or at least one (e.g., protease-specific) amide bond (see [00022]-[00023]). For the purposes of compact prosecution and applying prior art, claims 1, 34-37, 41, 45, and 48 are broadly interpreted to encompass any non-releasable and/or resealable linker having a carbon-carbon bond or amide bond; and/or at least one disulfide (SS), at least one ester (e.g., O(C=0)), and/or at least one (e.g., protease-specific) amide bond within its structure.
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 3, 4, 7, 13, and 48 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 pre-AIA the applicant regards as the invention.
For claims 3, 4, 13, and 48: With regards to the limitation “compound is delivered to one or more damaged, low density, or weakened bone sites”; “compound identifies the one or more damaged, low density, or weakened bone sites”; “or a pharmaceutically acceptable salt thereof, to one or more damaged, low density, or weakened bone sites”, it is noted that the phrase is unclear for it may imply two reasons: (a) “damaged” or “weakened bone sites” may mean “bone fracture” or (b) “non-osteoporotic bone fracture”. For the sake of compact prosecution, the claims have been interpreted broadly, i.e., as treating (a) bone fracture in general and (b) other non-osteoporosis bone-related diseases requiring bone healing.
For claim 7: With regards to the limitation “wherein the therapeutically effective amount of the compound, or the pharmaceutically acceptable salt thereof, accelerates the treatment healing or repair of an osteotomy, a bone graft, or a bone fracture”, it is noted that the phrase is unclear for two reasons: (a) the bone fracture may mean “bone fracture” or “non-osteoporotic bone fracture,” and (b) the limitation “osteotomy or bone graft” refers both to “bone fracture or other non-osteoporosis bone related disease” or only to “other non-osteoporosis bone related disease”. For the sake of compact prosecution, the claims have been interpreted broadly, i.e., as treating (a) bone fracture in general and (b) other non-osteoporosis bone related disease requiring osteotomy or bone graft.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 16, 18-21, 24-27, 29, 33-38, 40, 41, 44, 45, and 48 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 claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
Scope of the claims
The claims are drawn to compound administered comprising bone anabolic agent linked to bone-targeting ligand.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, several embodiments of the invention were reduced to practice:
In certain embodiments, X is a bone anabolic agent (e.g., an agent having bone anabolic
activity); in some embodiments, X is a bone anabolic agent that increases the production of collagen in the individual or improves the ability of the individual to form or process collagen. In some embodiments, X is a growth factor, a small molecule, a peptide, a protein, a hormone, or a fragment thereof, such as when attached to or released from a compound described herein. In some embodiments, X is a growth factor, a small molecule, a peptide, a protein, a hormone, or a fragment thereof, such as when attached to or released from a compound described herein. In some embodiments, X is a bone anabolic agent selected from the group consisting of an agonist of parathyroid hormone receptor 1, a parathyroid hormone (PTH), a PTH-related protein (PTHrP), and abaloparatide. In some embodiments, X is Ln2P3 (see [00017]). Additionally, the instantly claimed invention specifies In some embodiments provided herein, Z is a hydroxyapatite targeting ligand; in some embodiments provided herein, the hydroxyapatite targeting ligand includes a tetracycline, a phosphonate (e.g., a bisphosphonate (e.g., a mono-bisphosphonate, a tri -bisphosphonate, or a polybisphosphonate), an acidic oligopeptide, a ranelate, a pyrophosphate, or a targeting ligand developed through phage display (see [00020]). However, the constituents of the claimed compound are not represented in the reduction to practice.
The Specification does not disclose which sequence(s), domain(s), motif(s), structure(s), etc. must be present/retained by members of the claimed genus to allow for bone targeting. Instead, Applicant merely offers a cursory statement that any molecule having bone targeting ability will work.
In addition, the specification fails to include a reduction to practice of a composition including both the active therapeutic agents.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. MPEP 2163 (I)(A). The instant specification states that In some embodiments, the therapeutically effective amount of the compound, or the pharmaceutically acceptable salt thereof, reduces non-union or delayed unions of a bone (e.g., an osteotomy, a bone graft, or a bone fracture) in the individual (e.g., in need thereof, such as an individual having OI); in some embodiments, the therapeutically effective amount of the compound, or the pharmaceutically acceptable salt thereof, increases strength of a bone in the individual (e.g., in need thereof, such as an individual having OI) (see [00066]-[00067]). While the applicant details that the ability of an anabolic linked to a hydroxyapatite ligand to accelerate the repair of fractures in a Type 3 OI disease state was analyzed (see[00068]), the written description of improvement with treatment is not adequately supported with details or experimental examples with results.
Physical and/or chemical properties:
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the compound composition and therefore does not sufficiently describe an agent that activates an extracellular matrix component. Understanding the physical basis for having anabolic as well as bone-targeting ligand is critical to determining which of the compound that meets the bone repair or healing requirements of the genus also meet this additional functional requirement of the genus.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The Specification does not sufficiently describe a “bone targeting ligand”. The claims require a “bone targeting ligand”. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus to establish a structure-function relationship with respect to bone targeting. Also, the specification does not describe a general correlation between composition and structural coordinates for the claimed genus. It is noted that the recitation of a “bone-targeting molecule” describes what the molecule does—not what the molecule is. For example, claim 18 recites “Z is a hydroxyapatite targeting ligand”; claim 20 recites “is a linear chain of amino acid residues or a branched chain of amino acid residues”; claims 24 and 48 recite “Z is a bone targeting ligand comprising at least 4 amino acid residues having the same chirality”; claim 29 recite “Z is 20 repeating D-glutamic acid amino acid residues”. As a result, it is impossible to predict, based on the specification, how the combinatorial composition will affect the bone targeting activity relative to bone-forming biological activity.
Method of making the claimed invention:
Bone anabolic agents and its derivatives, as well as bone targeting ligands directed to hydroxyapatite-rich bone is well-known in the art. It is not disputed that one of ordinary skill in the art could synthesize or combine, albeit with route experimentation and optimization, the active compound provided that the composition is known. Where the specification fails to provide description is details in the composition to make. For example, the specific composition of each of the compounds, requirements for administration of the composition for treating/preventing bone fracture, bone healing, etc. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless combinations of both the compounds that meet the composition requirements of the claims would also have specific therapeutic efficacy with expected bone repair activity. The lack of written description about the method of treatment makes knowing if the inventor has possession of the composition at the time of filing inconclusive.
Conclusion:
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
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.
Claims 1, 16, 18-21, 24-27, 29, 33, 34, 40, 41, 44, 45, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over US 20210283227 (published on September 16, 2021) in view of EP 3498291 (published June 19, 2019).
US’227 discloses a drug delivery system comprising at least one peptide and a targeting ligand for bone fracture and/or for bone healing; some embodiments include a peptide delivery system comprising at least an acidic, basic, hydrophilic, hydrophobic or neutral peptide linked to an acidic peptide or nonpeptidic polyanion for use in targeting the aforementioned attached peptide to a bone fracture surface; in some embodiments, a conjugated peptide expresses an anabolic function that acts through PTH receptor 1, and various formats of targeting ligands guide the drug to raw hydroxyapatite (see Abstract). US’227 discloses that at least one compound of the formula X—Y—Z, or a pharmaceutically acceptable salt thereof, or a metabolite thereof, wherein X is at least one agent that modulates the activity of at least one of parathyroid hormone receptors; Z is at least one bone-targeting molecule; and Y is a linker that joins and/or links X and Z; in some embodiments, X is at least one agent that enhances the activity of at least one of parathyroid hormone receptors; Z is at least one negatively charged oligopeptide or an equivalent thereof that binds to hydroxyapatite and/or raw bone (see [0009]). SEQ ID NO: 25 of US’227 has 86.4% sequence identity to SEQ ID NO: 1 of the instantly claimed invention (see below):
PNG
media_image1.png
422
688
media_image1.png
Greyscale
Various aspects and embodiments disclosed by US’227 relate generally to the modelling, treatment, reducing resistance to the treatment, prevention, and diagnosis of diseases/symptoms induced by bone-related diseases. Embodiments include methods of treating a bone related disease, comprising the steps of: providing to a subject at least one therapeutically effective dose of a compound (see [0003]). However, US’227 is silent about specifically treatment of Osteogenesis imperfecta (OI).
EP’291 discloses a pharmaceutical composition for preventing or treating bone diseases comprising a fusion peptide in which a bone tissue-selective peptide bound to parathyroid hormone (PTH) or a fragment thereof, as an active ingredient (see claim 1); wherein the fusion peptide has a structure in which an N-terminus of the bone tissue-selective peptide is bound to a C-terminus of parathyroid hormone (PTH) or a fragment thereof (see claim 7); wherein the bone disease is selected from the group consisting of osteoporosis, osteogenesis imperfecta (see claim 8). EP’291 found that bone density was increased and bone generation effect was improved, as compared to parathyroid hormone (PTH), by injecting a pharmaceutical composition comprising a fusion peptide in which a bone tissue-selective peptide bound to parathyroid hormone (PTH) (see [0018]); and the group treated with the fusion peptide in which a bone tissue-selective peptide bound to PTH showed an increase in bone density (see FIG. 2, [0067]).
Regarding claims 1 and 48: US’227 discloses a method of treating a bone fracture, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound having a structure of: X—Y—Z wherein: Z is a peptide consisting essentially of glutamic acid residues, aspartic acid residues, or a combination thereof, the peptide having not less than 6 and not more than 40 amino acid residues; Y is a linker; and X is a bone anabolic agent, or a pharmaceutically acceptable salt thereof (see claim 13). US’227 teaches that the targeting ligands are usually acidic oligopeptide chains containing 4 or more acidic amino acid residues and they bind to hydroxyapatite and/or raw bone (see [0186]); wherein the acidic amino acid residues comprise L- or D-aspartic acid, L- or D-glutamic acid, or a combination thereof (see [0017]).
It would have been obvious to combine the teaching of EP’291 and US’227 before the effective filing date of the claimed invention by considering administration of pharmaceutical composition and biomaterial for preventing or treating bone diseases like OI or bone fracture or enhance recovery and formation of bone tissue with compounds comprising parathyroid hormone related peptide linked to glutamic acid residues, aspartic acid residues as an effective and stable peptide for bone repair as in the instantly claimed invention. One of ordinary skill in the art would have been motivated to utilize the drug delivery system taught by US’227, a method of treating a bone fracture modified for improved activity with a reasonable expectation of success because EP’291 specifically teaches peptide analogs can be used for improved osteogenesis effect. Thus, one skilled in the art can adjust the composition the compound that enhances the activity of at least one of parathyroid hormone receptors, at least one negatively charged oligopeptide that binds to hydroxyapatite and/or raw bone (see US’227 [0009]) for improved stability, selectivity to bone tissue and bone regeneration (osteoanagenesis) effect (see EP’291 [0008]).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Regarding claims 16 and 40: US’227 teaches a compound having a structure of: X—Y—Z wherein: Z is a peptide consisting essentially of glutamic acid residues, aspartic acid residues, or a combination thereof, the peptide having not less than 6 and not more than 40 amino acid residues; Y is a linker; and X is a bone anabolic agent, or a pharmaceutically acceptable salt thereof (see claim 1); wherein X is an agonist of parathyroid hormone receptor 1 (PTHR1) (see claim 8); wherein X is an agonist of parathyroid hormone receptor 1 (PTHR1) (see claim 15); X is at least one polypeptide having about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and/or 100% identity to a full length abaloparatide or analogs (see [0015]). US’227 specifies that the active anabolic peptide or the effective fragment thereof is selected from the group consisting of parathyroid hormone related peptide (PTHrP), parathyroid hormone (PTH), Abaloparatide and agonists thereof (see [0052]).
Regarding claim 18: US’227 discloses one compound of the formula X—Y—Z, where Z is at least one negatively charged oligopeptide or an equivalent thereof that binds to hydroxyapatite and/or raw bone (see [0009]).
Regarding claim 19: US’227 discloses Z is at least one mono-, bi-, tri-, tetra-, penta-, hexa-bisphosphonate, and/or multiple-bisphosphonate (see [0042]).
Regarding claims 20 and 21; US’227 teaches the compound, Z is at least one polypeptide wherein the acidic amino acid residues further comprises branched amino acid, and/or branched chains of amino acids (see [0018]); in some embodiment, the negatively charged oligopeptide is a linear acidic amino acid chain( see [0068]); in some embodiment, the negatively charged oligopeptide comprises least two branched acidic amino acid chains (see [0069]).
Regarding claims 24-27: US’227 teaches the compound, Z is at least one polypeptide comprising about 4 or more, from about 4 to about 100, from about 4 to about 50, from 4 to about 20….amino acid residues (see [0012]); wherein the acidic amino acid residues comprise L- or D-aspartic acid, L- or D-glutamic acid, or a combination thereof (see [0017]); Z is a peptide consisting essentially of glutamic acid residues, aspartic acid residues, or a combination thereof (see claim 1).
Regarding claim 29: US’227 specifies that in other aspects of the compound, the acidic oligopeptide may be no more than 20 L or D-glutamic acid (see [0155]).
Regarding claim 33: US’227 teaches a compound having a structure of: X—Y—Z
wherein: Z is a peptide consisting essentially of glutamic acid residues, aspartic acid residues, or a combination thereof, the peptide having not less than 6 and not more than 40 amino acid residues; Y is a linker; and X is a bone anabolic agent, or a pharmaceutically acceptable salt (see claim 1); wherein the therapeutically effective amount of the compound, or a pharmaceutically acceptable salt thereof, provides a therapeutically effective amount of the bone anabolic agent to the bone fracture (see claim 19); X is at least one polypeptide having about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and/or 100% identity to a full length abaloparatide or analogs thereof; and Z is at least one polypeptide comprising about 4 or more, from about 4 to about 100, from about 4 to about 50, from 4 to about 20, from about 4 to about 15, from about 4 to about 10 acidic amino acid residues (see [0015]); comprising at least 4 acidic amino acid residues and no more than 20 acidic amino acid residues (see [0066]); in some embodiment, acidic amino acid residues selected from the group consisting of glutamic acid, D-glutamic acid (see [0067]).
Regarding claim 34: US’227 teaches a compound having a structure of: X—Y—Z
wherein, Y is a non-releasable linker (see claim 5).
Regarding claim 36 and 45: As discussed above, US’227 teaches a compound having a structure of: X—Y—Z wherein: Z is a peptide consisting essentially of glutamic acid residues, aspartic acid residues, or a combination thereof, the peptide having not less than 6 and not more than 40 amino acid residues; Y is a linker; and X is a bone anabolic agent, or a pharmaceutically acceptable salt thereof (see claim 1); X is abaloparatide and agonists thereof (see [0052]); Y is a releasable linker or a non-releasable linker (see claim 14); conjugated with D-Glu20 (i.e., a liner polymer of 20 D-glutamic acids) (see [0111]). {Note: Instant specification states abaloparatide (e.g., PTHrP, Ln2P3, or the like) (see instant specification [000103])}.
Claims 35, 37, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over US 20210283227 (published on September 16, 2021) and EP 3498291 (published June 19, 2019) as previously applied to claims 1, 16, 18-21, 24-27, 29, 33, 34, 40, 41, 44, 45, and 48; and further in view of US 20210213135 (published on July 15, 2021).
The teachings of US’227 and EP’291 are discussed above. However, US’227 and EP’291 are silent about the releasable linker that have protease specific amide bond.
Therefore, regarding claim 37: It would have been obvious to combine the teaching of EP’291, US’227, and US’135 before the effective filing date of the claimed invention by considering administration of pharmaceutical composition and biomaterial for preventing or treating bone diseases like OI or bone fracture or enhance recovery and formation of bone tissue with compounds comprising parathyroid hormone related peptide linked to glutamic acid residues, aspartic acid residues by a releasable linker, as an effective and stable peptide for bone repair as in the instantly claimed invention. One of ordinary skill in the art would have been motivated to utilize the drug delivery system taught by US’227 a method of treating a bone fracture modified for improved activity modified as taught by US’135 with a reasonable expectation of success because EP’291 specifically teaches peptide analogs can be used for improved osteogenesis effect. Thus, one skilled in the art can adjust the composition the compound that enhances the activity of at least one of parathyroid hormone receptors, at least one negatively charged oligopeptide that binds to hydroxyapatite and/or raw bone (see US’227 [0009]) for improved stability, selectivity to bone tissue and bone regeneration (osteoanagenesis) effect (see EP’291 [0008]) with an effective releasable linker with protease-specific amide bond (see US’135 claim 29).
Regarding claim 35: US’135 teaches a compound, wherein the releasable linker comprises at least one releasable linker group, each releasable linker group being independently selected from the group consisting of …. a protease-specific amide bond (see claim 29). {Note: This is in direct correlation with the instant specification which states Y is a releasable linker ….and/or at least one (e.g., protease-specific) amide bond (see instant specification [00023])}.
Regarding claim 38: SEQ ID NO: 25 of US’227 has 86.4% sequence identity to SEQ ID NO: 1 of the instantly claimed invention (see below [A]) and SEQ ID NO: 27 of US’135 has 95.5% sequence identity to SEQ ID NO: 4 of the instantly claimed invention (see below [B]).
A.
PNG
media_image1.png
422
688
media_image1.png
Greyscale
B.
PNG
media_image2.png
182
642
media_image2.png
Greyscale
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KOYELI BANERJEE whose telephone number is (571)272-5751. The examiner can normally be reached Monday-Friday 8-4PM.
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, Melissa Fisher can be reached at (571) 270-7430. 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.
/KOYELI BANERJEE/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights