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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1 December 2025 has been entered.
Status of the Claims
The amendment filed 17 June 2026 is acknowledged. Claims 7, 8, 13, and 20-24 are currently under consideration.
Claim Interpretation
Claims 7, 8, 13, and 20-24 recite “a full length syndecan-3 antibody possessing specificity for a region at amino acid positions 45 to 384 of human syndecan-3 core protein” (e.g., see claim 7 lines 2-3). The specification does not provide a limiting definition for “specificity for a region” and the state of the art teaches the extracellular domain of SDC3 comprises heparin sulfate chains as evidenced by Gondelaud and Blum (see PTO-892 mailed 8 November 2024, in particular figure 1). Therefore, given the broadest reasonable interpretation “a full length syndecan-3 antibody possessing specificity for a region” will be understood as any antibody that binds directly or indirectly to SDC3 in the claimed region (see Definition: Region. Merriam Webster. Accessed online 20 January 2026, in particular definition 3a, b). For example, claim 7 encompasses both a structure that binds directly or alternatively indirectly (e.g., heparin sulfate chains) to the amino acids at positions 45-384 of human syndecan-3.
Withdrawn Rejections
In view of Applicant’s amendments the 35 USC 112(b) rejections of claims 7 and 22-24 are hereby withdrawn.
In view of Applicant amending claim 8 to recite an “antibody” as the structure the 35 USC 101 rejection of claims 8 and 13 is hereby withdrawn.
In view of Application 17/924,427 being abandoned the non-statutory double patenting rejection over said application is hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112(a)
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 7-11, 13, 14 and 20-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant's arguments filed 17 June 2026 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicant argues the specification supports a functional class relationship between extracellular SDC3 targeting and transport associated cellular behavior (see Remarks pg. 5, last full para). Applicant specifically points to polyclonal antibodies as evidence that binding to any region within the claimed domain results in the claimed function (see Remarks para spanning pgs. 5-6) and monoclonal antibodies as evidence that distinct epitopes within the claimed region have the claimed function (see Remarks pg. 5 last full para).
First, a polyclonal antibody is a population of antibodies not a single antibody. The ordinary artisan would understand a polyclonal antibody with the claimed function is not the result of every single antibody in the population rather is a subset of antibodies in the population. Therefore, the ordinary artisan would not be able to reasonably extrapolate a structure function correlation. Furthermore, Applicant discloses Proteintech 10886-1-AP (i.e., polyclonal) wherein the target immunogen is not representative of the breadth of the claimed region (i.e., missing residues 45-86 and 110-123 while including 28 additional residues).
Second Applicant discloses two monoclonal antibodies (i.e., ABIN7270679, R&D Systems MAB35391) one of which binds to amino acids 100-114 while the second antibody epitope is not provided (see Affidavit pg. 3 last row of Table). In addition, Applicants 2 monoclonal antibodies are not representative of the claimed genus of any monoclonal or multispecific antibody with the claimed specificity. To put another way, Applicant has not disclosed antibodies that bind to amino acid residues 45-85 or 205-225 perform the recited functions.
Third, Applicant appears to be suggesting that any antibody that binds the claimed domain will exhibit both the ability to cross the blood brain barrier and treat Alzheimer’s Disease (see Remarks para spanning pgs. 4-5, pg. 5, 2nd full para). Specifically,
“the data support a structure/function relationship whereby antibodies recognizing distinct epitopes within the extracellular domain of SDC3 exhibit a common phenotype characterized by endothelial internalization, BBB-associated transport, and brain localization following systemic administration” (see Remarks pg. 5, 2nd full para, emphasis added).
However, Applicant also states,
“Importantly, cellular binding and internalization of a ligand do not inherently predict productive transport across the blood-brain barrier. Many receptors are capable of ligand uptake without mediating transcytosis into the brain parenchyma” (see Remarks pg. 5, 1st full para, emphasis added).
Therefore, Applicant seem to acknowledge that the functions are independent; thus, BBB transport is not predictive of treating Alzheimer’s Disease and vice versa.
The 35 USC 112(a) (i.e., written description) rejection of claims 7, 8, 13, and 22-24 is hereby maintained.
Claim 7-11, 13, 14 and 20-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating Alzheimer’s Disease or a method of brain targeting comprising administering SDC3 antibodies FAB3539A, MAB2734, or AF2734 (see R&D Systems catalog nos.), does not reasonably provide enablement for administration of any full length anti-SDC3 antibodies that both specifically bind the 45-384 amino acid region of SDC3 and either treat AD (see claim 7) or cross the blood brain barrier (see claim 8). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Applicant's arguments filed 17 June 2026 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicant argues the specification supports a functional class relationship between extracellular SDC3 targeting and transport associated cellular behavior (see Remarks pg. 5, last full para). Applicant specifically points to polyclonal antibodies as evidence that binding to any region within the claimed domain results in the claimed function (see Remarks para spanning pgs. 5-6) and monoclonal antibodies as evidence that distinct epitopes within the claimed region have the claimed function (see Remarks pg. 5 last full para).
It is noted Applicant’s arguments regarding both the written description and enablement rejections were not separate.
In addition to the response above, it was known at the time of filing that the extracellular domain of SDC3 exists as both membrane and soluble form and is highly flexible thereby allowing a variety of conformations, and no crystal structure was available (see Non-final mailed 11/08/2026 para spanning pgs. 9-10, pg. 13, 1st para). De novo antibody design has several challenges including,
“difficulty in accurately predicting the conformation of CDR loops (especially those that are long and variable in length) as well as the structures of antibody-antigen complexes for which there are no initial crystal structures." (see Tiller and Tessier as cited on the PTO-892 mailed 11/08/2026, pg. 209, 1st full para).
Regarding bispecific antibodies encompassed by the instant claims,
"A related challenge for these nonconventional antibodies is the need to optimize the location for attaching additional variable domains because some locations that are optimal for stability may be suboptimal for binding. For bispecific antibodies with conventional architectures, the proper pairing of different light chains with their cognate heavy chains may be influenced by interactions between the CDRs [as suggested by (141)]. Thus, mutations in the CDRs that improve affinity or solubility may alter pairing efficiency (either positively or negatively), and need to be considered as part of the overall design process" (see Tiller and Tessier, pg. 209, 2nd para).
In addition it was known at the time of filing that protein interactions were highly unpredictable. Specifically,
"Globular interfaces, requiring tertiary structure on both sides of the protein-protein interaction (PPI), have fewer published success" (see Arkine as cited on the PTO-892 mailed 11/08/2026, pg. 1103, 1st col. 1st para).
Therefore, for the reasons set forth above (i.e., response to written description), the ordinary artisan would have to identify antibodies that bind to the claimed region, cross the blood brain barrier, and treat Alzheimer’s Disease. The highly flexible nature of SDC3, the unpredictability of protein interactions, and Applicant’s own suggestions (i.e., success in one endeavor is not predictive of success in the other) would result in undue experimentation. Therefore, Applicant is not enabled for the breadth of “full length anti-syndecan3 antibodies” (i.e., binding any portion of the claimed region, all monoclonal, or all multispecific antibodies) that bind the claimed region, traverse the blood brain barrier and/or treat Alzheimer’s disease. The 35 USC 112(a) (i.e., scope of enablement) rejection is hereby maintained.
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 8, 13, 22, and 23 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.
The scope of Claim 8 is unclear. First, while claim 8 is drawn to “a method” (line 1) and “delivering said ligand into the brain of a patient” (line 4), previous claim 10 specifies the delivery comprises, “attaching the mono- or bi specific antibody… on endothelial cells” and “via systemic circulation”. It is thus unclear if “delivering said ligand” is synonymous with “administration” or alternatively with the inherent property of antibody binding (i.e., attaching). To put another way, it is unclear if claim 7 drawn to a method wherein “delivering” is synonymous with administering or alternatively whether the “delivering” encompasses the process or mechanism by which the antibody crosses the blood brain barrier.
Claim 22 recite the limitation “the antibody with specificity for the region at positions 45-384 of human syndecan-3” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 is drawn to wherein the antibody is administered alone. The scope of alone is unclear. For example, is alone drawn to the timing of the dose or alternatively the composition itself. To put another way is a syndecan antibody administered from one syringe while a second agent is administered from a second syringe within the scope of “alone”, or alternatively, does “alone” limit the claim to wherein no additional agents are administered.
Applicant does not appear to have address the rejection set forth above and is therefore maintained for the reasons made of record.
The following rejections are necessitated by amendment.
Claim Rejections - 35 USC § 112(b)
Claims 7, 8, 13, and 20-24 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.
Claims 7, 8, 13, and 20-24 are drawn to “a full length anti-syndecan-3 antibody possessing specificity for a region at amino acid positions 45 to 384 human SDC3 core protein, UniProt 075056”. First, the scope of the antibody is unclear. For example is the recitation of “full length” in reference to syndecan 3 as the terms follow each other. To put another way, is the antibody required to recognize a full length syndecan 3 protein rather than a fragment of syndecan 3. Alternatively, is “full length” in reference to the structure of the antibody. In the case of the later the scope of the structure is unclear. For example, is an scFv, wherein the entire binding domain is located on a single chain within the scope of “full length”, or alternatively is the scFv outside the scope because it does not possess an Fc region. Given antibodies are comprised of multiple chains it is unclear if full length refers to a single chain or particular domains.
Second, Applicant’s amendments to include “UniProt O75056” as a reference for a syndecan 3 is unclear because that particular accession number has 197 entries and at least two sequence variations (see UniProt O75056, history). Therefore, the scope of the amino acid residues remains unclear. In addition, there are at least two splice isoforms of SDC3 comprising either a 28 amino acid substitution for amino acids 1-86 or a deletion of amino acids as evidenced by R&D Systems (see R&D Systems catalog no. AF3539, pg. 2, 1st para, as cited on the PTO-892 mailed 01/29/2026). Therefore, without a reference sequence it is unclear which residues are within the scope of the instant claims.
Claim 8 recites the limitation "said ligand" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Applicant's arguments filed 1 December 2025 have been fully considered but they are not persuasive.
Applicant argues the claims have been amended to correct each of the deficiencies listed above (see Remarks pg. 6, 5th para). However, for the reasons set forth above Applicant’s amendments do not overcome the 35 U.S.C. 112(b) rejection.
Therefore the 35 U.S.C. 112(b) rejection of claims 7, 8, 13, and 20-24 are hereby maintained.
Claim Rejections - 35 USC § 112(a)
New Matter
Claims 7, 8, 13, and 22-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 7, 8, 13, and 20-24 are drawn to “a full length anti-syndecan-3 antibody possessing specificity for a region at amino acid positions 45 to 384 human SDC3 core protein, UniProt 075056”.
The specification does not disclose “full length antibodies” nor “UniProt O75056”.
First, given the UniProt O75056 has 197 entries and discloses two sequences for syndecan 3. It is unclear if Applicant is referring to the O75076 entry from when Berndt was published, from the time of the foreign-priority document, from the time of the reply, or some other time (see Remarks pg. 6 last para). It is unclear what basis Applicant has for claiming UniProt O75056 is part of the original disclosure. Therefore, reciting a genus of antibodies that binds to a specific region of UniProt O75076 reaches beyond the specification as originally filed.
Conclusion
No claim allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/H.A.P./Examiner, Art Unit 1644 /AMY E JUEDES/Primary Examiner, Art Unit 1644
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