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 . 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.
Priority
The instant application is a continuation of PCT/US2022/041738 filed on 08/26/2022 and claims domestic benefit to US provisional applications 63/293,432 filed on 12/23/2021, 63/245,460 filed on 09/17/2021, and 63/238,013 filed on 08/27/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/04/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1-20 are pending and being examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
The specification filed on 02/23/2024 recites “… is 543 KB in size” on line 20 page 1. The size of the text file should be recited in bytes.
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 and 16-20 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 recites that the Mannose 6-Phosphate LigandC can be the following structure shown below:
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Here, the recited R47 is undefined in the claims, making it unclear what the scope of the R47 group is.
Claims 2-11 and 16-20 depend from claim 1, but do not overcome the described indefinite issue.
For purposes of examination, R47 is being interpreted as being selected from C1-C3 alkyl and C1-C3 haloalkyl as supported by the specification on line 8 page 13..
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16-18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 recites that the compound of claim 1 is of Formula shown below:
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Here, claim 16 depends from claim 1. Claim 1 only recites a R1 group in the structure shown below:
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Therefore, claim 16 fails to include all of the limitations of the claim upon which it depends because the recited compounds in claim 16 do not contain the additional X1 linkage.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Busch et al. (WO2021142377A2, in PTO-892 and publication date of 07/15/2021). Parish et al. (WO1990001938A1 in PTO-892).
Busch teaches a class of compounds that include a ligand moiety that specifically binds to a cell surface receptor such as mannose-6-phosphate receptor (M6PR) or asialogycoprotein receptor (ASGPR) (Abstract).
Busch teaches that their M6PR binding compound has the general structure shown below (claim 1):
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Specifically, Busch teaches that the M6PR binding moiety is the mannose ring structure as disclosed in paragraph 0049.
Busch teaches that W is a hydrophilic head group and can be selected from several groups including
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, -P=O(OH)2, and –OP=O(R3)(OH), wherein R3 can be H, C1-6 alkyl, or substituted C1-6 alkyl (paragraph 0113).
Busch teaches that the linking moiety Z1 connects the hydrophilic head group W to the mannose ring and is –(CH2)j wherein j is 1 to 3 (paragraph 00117). Furthermore, Busch teaches that the linking moiety Z2 can be O or S and links the mannose ring to the Ar group (paragraph 00118). Busch teaches that the mannose ring of the M6PR binding moiety can be incorporated into their compounds by attachment at the Z2 group position (paragraphs 0050-0051).
Busch provides exemplary M6P binding compounds in Table 1 (paragraph 00142) including the X19 synthon shown below:
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Here, the X19 synthon has the same base mannose 6-phsophate ligandC structure as the recited
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in the instant claims, and also the recited LinkerE structure when R11 through R13 are alkyl, R14 is -NR6-, wherein R6 is H, and R14 through R19 are bonds.
The X19 synthon shown in Busch does not recite a R55 group.
However, it would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the phosphate group on the X19 synthon disclosed in Busch with the
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moiety disclosed in Busch and further link this structure using an -O- linking moiety as disclosed in Busch to arrive at the claimed invention.
One of ordinary skill in the art would have substituted one known element (the phosphate group) for another (the moiety in Busch) to obtain predictable results and would have a reasonable expectation of success in doing so because Busch provides guidance that both the phosphate group and the recited moiety are suitable groups at this position to form the mannose 6-phosphate ligand compound.
One of ordinary skill in the art would have combined prior art elements according to known methods of linking the moiety in Busch using an -O- linking group to yield predictable results and would have a reasonable expectation of success in doing so because Busch provides guidance of using this -O- linking group to link various moieties onto the same base mannose structure.
In regards to instant claims 2-3, instant claims 2-3 depend from instant claim 1. Here, instant claims 2-3 only further limit the selection of the recited R5 group but does not require that the recited compound must be a M6P ligand that has the recited R5 group.
Therefore, since instant claim 1 is rendered obvious for a selected M6P ligand with a recited R55 group as described above, instant claims 2-3 are also rendered prima facie obvious.
Claim(s) 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Busch et al. (WO2021142377A2, in PTO-892 and publication date of 07/15/2021), as applied to claim 1 above, and further in view of Parish et al. (WO1990001938A1 in PTO-892).
The teachings of Busch are as described above and teach the compound of instant claim 1 as discussed above. Furthermore, Busch teaches that mannose-6-phosphate is a monosaccharide ligand that plays a key role in the intracellular retention and secretion of lysosomal hydrolytic enzymes to which they are attached, and that endocytosis by an M6PR allows for internalization into the cells of compounds being a mannose 6-phosphate ligand and trafficking to lysosomes (paragraph 0004).
Busch teaches that their compounds can be used to treat a disease or disorder by depleting certain proteins such as cell surface receptor proteins, transport proteins, and others by degradation through the lysosomal pathway (paragraphs 00379-00380). Busch teaches that the disease or disorder can be an inflammatory or autoimmune disease (paragraph 00384).
Busch does teach the same M6P ligandC structure as
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recited in instant claims 19-10 as discussed above. However, Busch does not teach the recited LinkerE is -OH.
Parish discloses phosphosugar-based anti-inflammatory and/or immunosuppressive drugs and methods of treatment thereof (Abstract).
Parish discloses that the administered phosphosugar is mannose-6-phosphate (claim 3).
As evidenced by lines 8-15 page 4 of the instant specification, mannose 6-phosphate is a known ligand for mannose 6-phophate receptor and has the structure shown below:
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.
Here, the mannose 6-phosphate of Parish has the same base mannose 6-phsophate ligandC structure as the recited
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except for the recited R55 group in the instant claims, and also contains the recited LinkerE structure when R11 is -O- and the rest of R12 through R19 is a bond.
Furthermore, Parish teaches that mannose phosphate receptor (MPR) mediate transport of lysosomal enzymes to lysosomes and these receptors functions not only in internal transport of lysosomal enzymes but is also important in their secretory pathway and their expression on cell surfaces (lines 27-35 page 1). Parish teaches that their present invention is based on the hypothesis that mannose-6-phosphate and related phosphosugar structures may act as anti-inflammatory agents in vivo possibly by depleting leukocytes of their lysosomal enzymes (lines 32-34 page 1 through lines 1-5 page 2). Parish further teaches that the mannose-6-phosphate may act as antagonists or competitive inhibitors of natural ligands of MPR on cells and act as anti-inflammatory agents that can be used to treat inflammatory diseases or conditions (lines 1-15 page 4).
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the 1’ position containing the -CH2-CH2-NH2 structure in the X19 synthon of Busch with the OH group of the M6P as disclosed in Parish to arrive at the claimed invention.
One of ordinary skill in the art would have substituted one known element (the -CH2-CH2-NH2 structure in Busch) for another (the OH group in Parish) to obtain predictable results and would have a reasonable expectation of success in doing so because both Busch and Parish teach their respective mannose 6-phosphate compounds perform the same function of binding to mannose 6-phosphate receptors. Furthermore, Parish provides additional guidance that the M6P binding compound itself has similar purposes of disrupting the lysosomal transport and for treating anti-inflammatory related diseases or conditions, suggesting that the ordinary skilled artisan would have considered using an M6P compound with an OH group at the 1’ position.
Allowable Subject Matter
Claims 12-15 are allowable. Claims 5-8 and 16-18 are free of the prior art and would be allowable if amended to overcome the 112b rejection over these claims.
The following is an examiner's statement of reasons for allowance:
The instant claims are directed toward compounds as defined by the recited Formula in instant claim 12.
The following reference is considered to be the closest prior art:
Busch et al. (WO2021142377A2, in PTO-892 and publication date of 07/15/2021)
The teachings of Busch are as described above.
Furthermore, Busch demonstrates the formation of an intermediate in Example 119 (paragraph 001202) to form their compounds as shown below:
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Here, Busch teaches N groups at the same positions to form compounds such as the one shown in paragraph 001205. However, the base sugar is not a mannose (different orientation of the OH and N groups) and the 2’ position contains an acetyl group which is not a recited R8 group.
Furthermore, the prior art does not teach or suggest the modification of the 1’ and 2’ position with the recited moieties in instant claims 12-15 on mannose 6-phosphate sugar compounds as well as the modifications to the mannose 6-phosphate compound as recited in instant claims 5-8 and 16-18.
Therefore, an ordinary skilled artisan before the effective filing date of the claimed invention would not have performed routine experimentation or optimization to arrive at the recited compounds of instant claims 5-8, and 12-18.
Conclusion
Claims 1-11 and 16-20 are rejected. Claims 12-15 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID H CHO whose telephone number is (571)270-0691. The examiner can normally be reached M-F 8AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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