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 .
DETAILED ACTION
The instant application is in response to the papers filed on July 29, 2026. Pursuant to the preliminary amendment filed on July 29, 2026, claims 7, 10, 12, 14, 15, 19-22, 31, 33-41 are pending in the application. Claims 7, 14, 20, 21, 31, 33-37 have been amended, claims 1-6, 8-9, 11, 13, 16-18, 23-30, and 32 have been cancelled, and claims 38-41 are newly filed in Applicant’s amendment filed on June 21, 2021.
Applicant’s election without traverse of the invention of Group II, e.g., claims 31, 38-41, drawn to a method of treating Alzheimer’s disease, in the reply filed on July 29, 2026 in response to the restriction requirement filed on May 5, 2026 is acknowledged.
Claims 1, 3-7, 10, 12, 14, 15, 19-22, 33-37,are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution. The requirement for restriction between Groups I-IV is maintained for reasons of record, and hereby made FINAL. Applicant timely responded to the restriction (election) requirement in the Paper filed on July 29, 2026 by paying for a month extension of time under 37 CFR 1.17(a)(1).
Therefore, claims 31, and 38-41 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to European Patent Application No. 21183382.7 filed on July 2, 2021 and PCT Application No. PCT/EP2022/068235filed on July 1, 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.Thus, the earliest possible priority for the instant application is July 2, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 6, 2024 and December 16, 2024 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or an official IDS, they have not been considered.
The disclosure is objected to because of the following informalities:
The reference to Fig. 1A in paragraph 290 appears incorrect as it should be Fig. 11D.
Secondly, in paragraph 290, the recitation of “SORLA™” is not proper as there is no Trademark for SORLA.
The reference to Fig. 1D in paragraph 291 appears incorrect as it should be Fig. 11B.
Appropriate correction is required.
Claim Objections
Claim 31 is objected to because the recited abbreviation, “SorLA”, should be spelled out at the first encounter in the claims.
Claim 38 is objected to because the recitation, “wherein the SorLA mini-receptor is no longer than 685 amino acids” should recite the similar language of “comprises no more than…” as recited in claim 31 from which claim 38 depends when describing the SorLA receptor size. This is proper to reduce confusion as to the structure of the SorLA receptor employed in the method of treatment. Appropriate correction is required.
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 31, and 38-41 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 31 recites a method of treating Alzheimer's Disease, the method comprising administering to an individual in need thereof the polynucleotide construct encoding a SorLA mini-receptor comprising: a. an amino acid sequence that is at least 80% identical to one or more of the amino acid sequences selected from the group consisting of SEO ID NO: 11, SEO ID NO: 12, SEO ID NO: 13, SEO ID NO: 14, SEO ID NO: 15, and SEO ID NO: 16; b. an amino acid sequence that is at least 80% identical to the amino acid sequence of SEO ID NO: 17; and c. an amino acid sequence that is at least 80% identical the amino acid sequence of SEO ID NO: 18; wherein the SorLA mini-receptor comprises no more than 700 amino acids.
The specification does not provide an enabling disclosure for treating Alzheimer's Disease, in which the method is comprising administering to an individual in need thereof the claimed composition.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claim. The treatment of Alzheimer's Disease, as claimed, to the extent of its scope would require undue experimentation.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The breadth of the claims and (2) The nature of the invention. The claims are directed to a method, particularly claims 31 is directed to a method of treating Alzheimer's Disease, the method comprising administering to an individual in need thereof a polynucleotide construct encoding a SorLA mini-receptor. The receptor is describes as being encoding an amino acid sequence that is at least 80% identical to one or more of the amino acid sequences selected from the group consisting of SEO ID NO: 11, SEO ID NO: 12, SEO ID NO: 13, SEO ID NO: 14, SEO ID NO: 15, and SEO ID NO: 16; and further comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEO ID NO: 17 and 18. The scope encompasses any routes of delivery for the individual, e.g. ingestion via the oral route, intranasal, rectal, inhalation, topical or injection, such as intravenous, subcutaneous, intramuscular, intraperitoneal, intracranial and spinal injection. The method is not limited by any dosage form, e.g. tablet, capsule, and liquid, quantity, and/or frequency of administration. The composition is also not limited by the type of delivery, i.e. viral, and the use of any carriers or excipients. Furthermore, the claims encompass any individual in need thereof for treatment of Alzheimer’s disease. There is are limitations presented in reference to the patient having any particular symptom or rather stage of Alzheimer’s disease and representing any range of ages.
The nature of the invention is to treat Alzheimer’s diseases, yet there are no particulars recited in the claims to obtain this outcome effectively. The Specification describes that SORLA (Sortilin-related Receptor with A Type Repeats) is well known to be associated with Alzheimer's disease (AD), yet the focus of the invention is on the SORLA mini-receptor for treatments, wherein select domains have been removed (Fig. 1A).
(3) State of the prior art. The prior art is extensive in the knowledge of Alzheimer’s Disease, the respective methods of treatments, and furthermore the molecular biology (function and structure) of the SORLA receptor in relation to such disease. The prior art does not teach the claimed composition of the SORLA mini-receptor wherein the amino acid length is no greater than 700 amino acids as it does not comprise VPS10p, YWTD, CR domains, and a propeptide for use in treating Alzheimer’s disease. In relation to the full length sequence which is depicted in Fig 1A, Anderson et al. (Proc Natl Acad Sci USA. 2005; 102(38):13461-6; of record IDS) describes SorLA acts as a sorting receptor that protects amyloid precursor protein (APP) from processing into amyloid β-peptide, and thereby reduces amyloidogenic peptide formation based on a combination of in vitro and in vivo work, stating “Consequently, reduced receptor expression in the human brain may increase Aβ production and plaque formation and promote spontaneous AD [Alzheimer’s disease]” (abstract).
The instant Specification states, the mini-receptor does not harbor the CR-domains required for the direct binding of the APP protein as described in Mehmedbasic et al. 2015 (abstract, of record IDS), nor the VPS10p-domain suggested to bind the amyloid-β (Aβ) peptide as described in Kitago et al. 2015 (of record IDS), and therefore the remaining part of SORLA which constitutes the mini-receptor is being investigated. Moreover, as seen in Fig. 1, both the YWTD domain and propeptide are also not included in the claimed receptor. Altogether, the prior art has shown that SORLA is connected to AD, yet the biochemical process remains unclear as to what domains are required for receptor function and/or treating AD. Furthermore, it is not clear if the outcomes observed by the Applicant, particularly those with the claimed composition, would translate into the same or rather similar outcomes observed in the prior art with the full structure SorLA receptor for treating AD. There remains much unpredictability with the full scope presented in the claims.
Lastly, claim 31 is not limited to the six 3Fn domains that are comprised in the wild type SORLA, but rather only recites “to one or more of…”, yet the prior art includes all six 3Fn domains, and particularly the ones listed in SEQ ID NOs: 11-16 as opposed to multiple copies of the same 3Fn domain sequence(s).
(4) The level of one of ordinary skill. There is a high level of skill required to appropriately clone the mini-receptor, formulate the pharmaceutical composition, then prepare, organize, and conduct trials to determine dosages and overall efficacy in treating AD after analysis of the collected data.
(5) The level of predictability in the art. The art is unpredictable. As stated above, the method and corresponding composition recited in claim 31 has not been administered to any individual, and moreover has not been shown to reduce symptoms or overall disease severity of AD. Additionally, it has not been shown in the Specification that specific SORLA domain(s) are required for effectively treating AD, and that the claimed composition which has fewer domains and are not recited in a particular structural order, would have similar outcomes in treatment of AD. Secondly, studies conducted on outcomes related binding and or expression of the claimed SorLA mini-receptor would not necessarily translate into therapeutic outcomes without providing in vivo assays of such receptor in the context of treating AD.
(6) The amount of direction provided by the inventor; (7) The existence of working examples of working examples.. The Specification describes in Example 4, “A Method for Viral Delivery of SORLA-3Fn to Cultures of Primary Neurons from Mice and Human iPSC-Derived Neurons” with the aim of “Providing evidence that viral delivery of the mini-receptor reduces amyloidogenic processing in neuronal cultures as it does in cultured cell lines.” The composition employed would be prepared in AAV9 vector, yet there is no mention of the mode of delivery and related dosages. There is no further mention of modes or delivery nor such dosages in the remaining disclosure, nor related conditions required of clinical trials such as determining improvements and/or conditions required to be a subject for treatment of AD.
Example 1 describes the generation of the SORLA mini receptor used in the assays/studies which is depicted in Fig 1, and listed as SEQ ID NO:22 or 10 (includes the FLAG peptide listed as SEQ ID NO:21). SEQ ID 22 and 10 both contain all of SEQ ID NOs 11-18 in sequential order, particularly SEQ ID NOs 11-16 being the FnIII (1-6) domains, SEQ ID NO: 17 being the transmembrane domain, and SEQ ID NO: 18 being the cytoplasmic tail. The working examples are based on all 6 FnIII domains being present with the transmembrane domain and cytoplasmic tail.
Example 2 describes the claimed receptor as having no effect on the non-amyloidogenic processing (as sAPPα is not altered), but can specifically decrease the level of the amyloidogenic products (sAPPβ and Aβ), and then stating the findings support a promising therapeutic effect of delivering the mini-receptor to the brain of AD patients. In summary, there are no working examples provided in the Specification of treating AD in an individual in need thereof.
(8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. There would be extensive experimentation required to determine the appropriate compositions for treating AD, such as which domains are necessary and in what order. Furthermore, it would require extensive experimentation to solely determine the appropriate vectors that could solely target brain neurons wherein expression levels are adequate for treating AD wherein excipient/carriers are included, and in view of the vector, including the necessary regulatory elements for expression to be adequate in the target netuons.
Conclusion: The method of treating AD in an individual in need thereof is not full enabled. Secondly, the claimed composition should be limited to the structure recited in Fig 1, and comprised in SEQ ID NO 10 and 22 as there is no support for currently claimed composition that allows for any combination of 3Fn domains.
Conclusion
Claims 31, and 38-41 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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, Maria G Leavitt can be reached at (571) 272-1085. 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.
/MICHAEL ANGELO RIGA/ Examiner, Art Unit 1634
/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
Prosecution Insights