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
The instant application, filed on 12 July, 2023, claims domestic benefit to US provisional application no. 63/388,887, filed on 13 July, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 29 May, 2026 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 13 February, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 09 February, 2024 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 29 May, 2026 has been entered in full. The response is an amendment to Restriction requirement to the claim set filed on 09 February, 2024. In the amendment, claims 121-127 and 129-139 are previously presented, claims 1-120 are cancelled, and claim 128 and 140-142 are withdrawn, however claims 140-142 read upon the elected species and will therefore examined. Therefore, claims 121-142 are pending and are the subject of this Office Action.
Election/Restrictions
Claim 128 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 29 May, 2026.
It is noted in the reply the applicant elected the species of wherein the autoantigen is PLA2R and the [Xn-L] has the following structure:
PNG
media_image1.png
85
566
media_image1.png
Greyscale
Which subsequently elects the siglec ligand’s structure:
PNG
media_image2.png
94
381
media_image2.png
Greyscale
And the linker structure:
PNG
media_image3.png
106
350
media_image3.png
Greyscale
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.
Claims 122, 123 and 130 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 122 and 123 recites the engineered autoantigen is of the formula (1): [Xn-L]m-Y wherein m is an integer 2 or more (3 or more in claim 123). As such the claim reads as repeated units of the sialic acid and linker in a long chain attached to a single antigen, however in the specification, none of the examples presented represent this structure, but instead show multiple sialic acid and linker unit attached to an antigen at various places (See figure 1 and 2). For the purpose of further examination and in light of the specification the claim will be interpreted to allow for repeated units can be linked to the antigen at various site and not linked in a long chain.
Claim 130 recites the limitation "wherein the linker attaches the sialic acid to the biotherapeutic". There is insufficient antecedent basis for this limitation in the claim, as a biotherapeutic is not recited earlier in the claim or in claim 121 from which it depends.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 121, 132, and 140 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Reilly et al. (2008) Bifunctional CD22 Ligands use Multimeric Immunoglobulins as protein Scaffolds in Assembly of Immune Complexes on B Cells J. Am. Chem. Soc. 130, 7736-7745.
In regard to claims 121 and 140 O’Reilly anticipates a bifunctional ligand (engineered autoantigen) comprising hapten nitrophenol (antigen) and the CD22 ligand BPC-NeuAcα2-6Galβ1-4GlcNAc (siglec ligand) (pg.7737, col 2, lines 7-14/ Figure 1).
In regard to claims 132 and 140 O’Reilly anticipates the autoantigen comprising a polypeptide (Figure 1).
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.
Claims 122-131 are rejected under 35 U.S.C. 103 as being unpatentable over O’Reilly as applied to claim 1 above, and further in view of Prescher et al. (2014) Discovery of Multifold Modified Sialosides as Human CD22/Siglec-2 Ligands with Nanomolar Activity on B-cells ACS Chem. Biol 9, 1444-1450, Rillahan et al. (2014) Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukemias and B cell lymphomas Chem. Sci. 5, 2398-2406, Bhat et al. (WO 2012/007896), and Alas et al. (2021) Peptide-Drug Conjugates with Different Linkers for Cancer Therapy J. Med. Chem. 64, 216-232.
O’Reilly teaches a bifunctional ligand (engineered autoantigen) comprising hapten autoantigen and a siglec ligand as outlined above.
In regards to claim 122 O’Reilly teaches the bifunctional ligand has the structure of formula (I) of the instant application () as shown below in examiner figure 1.
PNG
media_image4.png
185
413
media_image4.png
Greyscale
Examiner Figure 1: Screenshot of Scheme 1 bifunctional ligand annotated.
In regards to claims 122 and 123, while not distinctly teaching attaching multiple siglec ligand and linker to the antigen, O’Reilly teaches higher concentrations of the siglec ligand increase complexing with CD22 (pg.7742, col 2, lines 18-27 /Figure 4).
In regards to claim 126 O’Reilly teaches X has the structural formula of (II) of the instant application in which the R4 group is [1,1’ – Biphenyl]-4-carboxamide (a substituted alkylamide), R3 is an amino acyl , R2 is a hydroxyl, and R1 is hydrogen.
O’Reilly fails to teach the lack of a polysaccharide in the linker of the siglec ligand of claims 124 and 125, the linker comprising a polyethylene glycol group of claim 127, and the ligand having the first structure of claim 129. Further O’Reilly fails to teach the linker of claim 130, and the siglec ligand with the linker of claim 131.
Prescher, however, in regards to claims 124 and 125 teaches a siglec ligand in which they do not contain saccharides and instead try various substitutions in place of the saccharides (Table 4), Further Prescher teaches saturated more flexible propyl groups in substitution in the location of the saccharide in O’Reilly showed higher affinity to the target siglec (pg.1446, col 2, lines 41-pg. 1447, col 2, line 1).
Prescher, fails to teach the linker comprising a polyethylene glycol group of claim 127, the ligand having the first structure of claim 129, the linker of claim 130, and the siglec ligand with the linker of claim 131. Rillahan, however, in regards to claim 129 and 131 teaches the substitution of the 4-biphenyl group like the one in O’Reilly with a 3-phenoxybenzamide group (Figure 3A), results in more increased selectivity of the siglec ligand to the target human CD22 ligand (siglec-2) with comparable avidity for effective targeting of B-lymphoma cells (pg.2402, col 2, line 8 - pg.2403, col 1, line 9/Figure 3B).
RIllahan, fails to teach the linker comprising a polyethylene glycol group of claims 127 and 129, the linker of claim 130, and the polyethylene glycol group with the linker of claim 131.
Bhat, however, in regards to claim 130 teaches likers in bifunctional therapeutics are composed of three part, a region to attach the effector moiety (siglec ligand), a spacer region, and a region to attach to the antibody (autoantigen) (pg.19, lines 14-17). In regards to the region to attach the effector moiety Bhat teaches it must enable a specific directional covalent linking strategy (pg.19, lines 22-23) and teaches a this can be done when the region is a pentafluorophenyl ester, which allows the pentafluorophenol to act as a leaving group and effector moiety to link to the C=O group (see below) (pg.20, lines 4-10).
PNG
media_image5.png
139
412
media_image5.png
Greyscale
In regards to claims 127 and 129 Bhat teaches the spacer region provides overall length to the linker and can be polyethyleneglycol acid (pg.21, lines 10-15). Alas also teaches the use of a Polyethylene glycol spacer and further highlight the repeating PEG units allow for increased solubility (Figure 12).
In regards to claim 130 Alas also further teaches the use of a triazole group (N3) in peptide drug conjugates because they are non-cleavable bonds which provide stability of the conjugate structure (pg.228, col 1, lines 16-19) and further as appropriate for cases where payload release is not necessary (pg.228, col 2, lines 24-27).
Together O’Reilly, Prescher, Rillahan, Bhat, and Alas teach all the components of structure 1 of instant claim 131 and further how these substitutions improve the ligand for various purposes.
Thus, O’Reilly discloses O’Reilly discloses a bifunctional ligand comprising a autoantigen polypeptide and a siglec ligand, Prescher teaches substituting bulky saccharides with saturated flexible propyl groups increased siglec ligand affinity, Rillahan, teaches the substitution of the 4-biphenyl group like the one in O’Reilly with a 3-phenoxybenzamide group increases selectivity of the siglec ligand to the target human CD22 ligand, and Bhat and Alas teach that polyethylene glycol serves as a linker spacer which can add length and further increase solubility, as well as the functional binding regions for bother the effector moiety and the antigen. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to try the combination of teachings to find an optimized siglec ligand with a reasonable expectation of success to develop a ligand with increase solubility, affinity and selectivity for a more effective treatment in diseases characterized by the need of increased antibodies against an autoantigen.
Claims 133-139, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over O’Reilly et al. as applied to claims 121, 132, and 140 above, and further in view of Duong et al. (2010) Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo J. Exp. Med. 207(1) 173-187, Ramachandran et al. (2016) PLA2R antibodies, glomerular PLAs R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians Nephrol Dial Transplant 31: 1486-1493, and Leonard et al. (2004) Epratuzumab, a Humanized Anti-Cd22 Antibody, in Aggressive Non-Hodgkin’s Lymphoma: Phase I/II Clinical Trials Results Clinical Cancer Research 10, 5327-5334.
O’Reilly fails to teach the autoantigen being a PLA2R of claim 133 and 137, the pharmaceutical composition for treating an individual having an autoimmune disease wherein the administration results in a reduction of antibodies against the antigen in the individual of claims 134 and 135, the autoimmune disorder selected from the list of claim 136, and more specifically membranous neuropathy of claim 137, and the siglec binding polypeptide comprising an antibody of claim 141.
Duong, however in regards to claims 134 and 135 teaches administering to mice a pharmaceutical composition comprising hapten nitrophenol and a siglec ligand (figure 2A) wherein the additions of siglec ligand with the antigen decreased the amount of anti- hapten nitrophenol antibodies (figure 2B and 2C) and further reduced immune response upon subsequent immunization (pg.176 , col 1, lines 15-23).
Duong fails to teach the autoantigen being a PLA2R of claim 133 and 137, and the autoimmune disorder selected from the list of claim 136, and more specifically membranous neuropathy of claim 137.
Ramachandran, however, teaches membranous nephropathy (MN) is an important cause of nephrotic syndrome in adults (pg.1486, col 2, lines 1-2), and anti-PLA2R antibodies significantly correlate with clinical activity of MN (pg.1486, col 1, lines 1-3). Further Ramachandran teaches that reductions of anti-PLA2R antibodies is associated beneficial for treatment (pg.1486, col 2, lines 7-11).
Ramachandran fails to teach the delivery schedule of claims 138 and 139 and the siglec binding polypeptide comprising an antibody of claim 141, however Leonard teaches the delivery of an anti-CD22 (siglec 2) antibody in human subject once a week for a month (pg.5328, col 2, lines 27-31) and demonstrates the binding to CD22 did not have any dose limiting safety issues (abstract).
Thus, O’Reilly discloses a bifunctional ligand comprising a autoantigen polypeptide and a siglec ligand, Duong teaches administration of a combination therapeutic comprising the autoantigen and a siglec ligand decreases the amount of antibodies against antigen and bolsters response on subsequent immunization, Ramachandran teaches membranous nephropathy is a disease whose progression is associated with antibody concentration of antibodies against autoantigen PLA2R, and further that decreasing these antibodies is associated with treatment of the disorder, and Leonard teaches administration of an antibody which binds to CD22 once a week for a month did not have any dose limiting safety concerns. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of O’Reilly, informed by the teaching of Duong to use the bifunctional ligand to reduce anti-antigen antibodies with the teachings of Ramachandran that membranous nephropathy would benefit from treatment which results in the decrease of anti-PLA2R antibodies, and the teachings of Leonard on dosing and the effectiveness of and anti-CD22 (siglec 2) antibody to simply substitute the antigen of O’Reilly and Duong with PLA2R (in regards to claims 138 and 139) or simply substitute the siglec ligand of O-Reilly with the anti-CD22 antibody of Leonard (in regards to claim 141), with a reasonable expectation of success to develop a safe and efficient pharmaceutical composition for the treatment of membranous nephropathy, which will reduce anti-PLA2R antibodies and would have a sustained effect in the event of subsequent relapse.
Claim 142 is rejected under 35 U.S.C. 103 as being unpatentable over Duong et al. in view of Engqvist and Nielsen (2015) ANT: Software for Generating and Evaluating Degenerate Codons for Natural and Expanded Genetic Codes ACS Synthetic Biology (4) 935-938.
Duong teaches a bifunctional ligand (engineered autoantigen) comprising hapten nitrophenol (antigen) and the CD22 ligand (siglec ligand) (pg.175, col 2, lines 4-14) which binds to b-cells and suppresses their activation (abstract).
Duong does not teach the nucleic acid sequence that encodes the fusion protein of claim 142, however, Engvist teaches a software which can use the well-established degeneracy of the genetic code to translate amino acid sequences into nucleotide sequences by determining optimal degenerate codons (abstract).
Thus, Duong discloses a bifunctional ligand comprised of a antigen and a siglec ligand which binds to b cells and suppresses their activation, and Engvist teaches a software that would enable a person of ordinary skill in the art to translate an amino acid sequence from a protein into a nucleotide sequence using the degeneracy of the genetic code. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the bifunctional ligand of Duong and method of determining the genetic sequence of the fusion protein of Engvist with a reasonable expectation of success to obtain a nucleic acid encoding the bifunctional ligand for improved protein engineering.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 121-124, and 126 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15, 20, 43, 48, 51, and 52 of U.S. Patent No.8,357,671. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 14, 15, 20, 43, 48, 51, and 52 of the U.S. patent all recite claim to structures which comprise siglec ligands linked with linkers with carriers, wherein the carriers can be antigens. Further the siglec ligands have the structural formula of instant application formula (II). This completely encompasses the instant applications claims 121-124, and 126.
Claims 121-124, and 126 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No.10,994,006. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the U.S. patent all recite claim to a structure which comprises siglec ligands linked with linkers with an antigens. Further the siglec ligands have the structural formula of instant application formula (II). This completely encompasses the instant applications claims 121-124, and 126.
Claims 121-125, 127-131, and 134 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 105, 108-114, and 119 of copending Application No. 18/036,844 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 105 of the reference application recites claim to an engineered biotherapeutic with a biotherapeutic (antigen) engineered elevated amount of siglec ligand with a formula of [Xn-L]m-Y wherein n is an integer of 1 or more and m is an integer od 3 or more. This fully encompasses instant application claims 121, 122, and 123.
Claims 108 and 109 of the reference application recite the siglec ligand does not contain a saccharide. This fully encompasses instant application claims 124, and 125.
Claims 110 of the reference application recites the linker comprises a polyethylene glycol group. This fully encompasses instant application claim 127.
Claim 111 of the reference application recites the linker is branched with one of more branching group. This fully encompasses instant application claim 128.
Claim 112 of the reference application recites identical structures for the siglec ligand as instant application claim 129.
Claim 113 of the reference application recites identical structures for the linker as instant application claim 130.
Claim 114 of the reference application recites identical structures for the siglec ligand as instant application claim 131.
Claim 119 of the reference application recites claim to a pharmaceutical composition comprising the engineered biotherapeutic and a pharmaceutical excipient. This fully encompasses instant application claim 134.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday – Friday from 8:30am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center to authorized users only. Should you have questions about access to the USPTO patent electronic filing system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via a variety of formats. See MPEP § 713.01. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/InterviewPractice.
/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights