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 .
It is noted that Examiner for the present application has been changed. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Examiner Masudur Rahman.
Claim Status
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 11/17/2023, in which applicant; amended claims 7, 14-15, 18-22, 29, 36; canceled claims 2-3, 5-6, 9-10, 12-13, 24-25, 27-28, 31-32, 34-35, 37-44.
Therefore, claims 1, 4, 7-8, 11, 14-23, 26, 29, 30, 33, and 36 are pending in the application.
Election/Restrictions
Applicants’ election without traverse of Group VII, claim(s) 30 and 36, drawn to a method for treating a mammal having a TDP-43 proteinopathy in the reply filed on 29 July 2026 is acknowledged.
Claims 1, 4, 7-8, 11, 14-23, 26, 29, and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
In the reply, Applicant elects: IPO13 as a species of IPO polypeptide and SEQ ID NO:5 as a single polypeptide sequence, SEQ ID NO:6 as a species of nucleic acid, and intrathecal as a species of administration. However, claims 30 and 36 do not recite the elected IPO13 polypeptide species SEQ ID Nos: 5 and 6. To expedite the prosecution, the examiner considers such identification to be an apparent inadvertent error (MPEP § 809.02(a) and 821).
Therefore, claims 30 and 36 are under current examination.
Priority
This application was filed 11/17/2023 and is a 371 application of PCT/US2022/031024 filed on 05/26/2022, which claims benefit to the Provisional Application 63256318 and 63193927 filed on 10/15/2021 and 05/27/2021 respectively.
Thus, the earliest possible priority for the instant application is 05/27/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/23/2024, 02/13/2025, and 07/29/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, and the signed and initialed PTO Forms 1449 are mailed with this action.
New Claim Rejections - 35 USC § 112(a)
(Written Description)
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 30 and 36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As per MPEP 2163(I), "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Also, as per MPEP 2163.03(V), there is a presumption that an adequate written description of the claimed invention is present in the specification as filed.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Possession may be shown in a variety of ways, for example, possession may be shown by describing an actual reduction to practice of the claimed invention. A specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) ("[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim."); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) ("[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose."); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves). Alternatively, applicant may present that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it").
Finally, MPEP 2163.04 describes the burden on the examiner with regard to the Written Description requirement, stating that in rejecting a claim, the examiner must set forth express findings of fact which support the lack of written description conclusion. These findings should:
(A) Identify the claim limitation(s) at issue; and
(B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed.
Dependent claim 30 encompass a genus of a nucleic acid sequence encoding any fragment of said IPO13 polypeptide.
Dependent claim 36 encompass any fragment of said IPO13 polypeptide consists of the amino acid sequence set forth in one of SEQ ID NOs: 56-77.
Teachings of the Specification:
In the specification Applicant discloses the IPO13 polypeptide fragment can be any appropriate length (e.g., can include any number of amino acids) provided that it maintains at least some function of a naturally occurring IPO13 polypeptide (e.g., the ability to reduce at least some TDP-43 aggregation and/or restore at least some nuclear localization of TDP-43 polypeptides(p. 47 lns 9-12). Applicant further discloses the IPO13 polypeptide fragment provided herein can include the amino acid sequence set forth in any one of SEQ ID NOs: 56-66 with zero, one, two three, or more (e.g., five, eight, 12, 15, 18, 20, 25, 30, 35, 40, or more) amino acid substitutions (e.g., one or more K[Wingdings font/0xE0]R substitutions) within the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), with zero, one, two, three, four, or five amino acid residues preceding the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), and/or with zero, one, two, three, four, or five amino acid residues following the articulated sequence of the sequence identifier (e.g., any one of SEQ ID NOs:56-66), provided that the IPO13 polypeptide fragment retains at least some activity exhibited by a naturally-occurring IPO13 polypeptide (e.g., the ability to reduce at least some TDP-43 aggregation and/or restore at least some nuclear localization of TDP-43 polypeptides) (p. 53 lns 2-12). Therefore, disclosure does not support the full claim scope of identity of any fragment of said IPO13 polypeptide, it has support for 100% identity to the SEQ ID NOs 56-77.
Working examples of the specification:
Claims 30 and 36 encompass a genus of any fragment of said IPO13 polypeptide, however, SPEC only describes only a subset of β-importins can reduce TDP-CTF aggregates, although importins and exportins interact with Nup62 and other FG-Nups during nuclear transport. IPO13 reduces TDP-CTF aggregation even more strongly that KPNB1 (Figure 19A, 22G). All three exportins strongly associated with Nup62 aggregates, but without affecting their morphology, whereas IPO13 caused strong dissociation and TNPOl partially disassembled TDP-CTF into smaller aggregates (Figure 22G). These results indicate that specific transport receptors have a similar effect on the formation of both TDP-43 and Nup62 aggregates, suggesting a common mechanism. Therefore, the genus of a nucleic acid sequence encoding any fragment of said IPO13 polypeptide is insufficiently detailed written description to show that Applicant had claimed a genus of fragments recognizes amino acid sequence identity to SEQ ID NOs: 56-77.
State of the Art at the Time of Filing:
The claimed invention is not well established at the time of filling. Although, one of skill in the art would neither expect nor predict the appropriate functioning of the any fragment that the recognizes any fragment of said IPO13 polypeptide as is claimed. Rudikoff et al. (PNAS, 79(6), pp.1979-1983,1982; cited in PTO892; hereinafter “Rudikoff”) teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. While CDR mutation might be expected to alter antigen binding of an antibody, framework mutations can also have an effect. Therefore, Rudikoff evidence that even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Panka et al. (PNAS, 85(9), pp.3080-3084, 1988; cited in PTO892) teach that a single amino acid difference in a framework residue at the boundary with CDR3 was responsible for the decreased affinity of an anti-digoxin antibody (Pg. 3083, Column 1, Paragraph, first partial). Similarly, in regard to the genus of antigen-binding fragments that specifically bind to B7-H6 Zhang et. al (J Immunol (2012) 189 (5): 2290–2299, cited in PTO 892) the ordinary skilled artisan would have been motivated to produce activate the immune cell. In regard to the reasonable expectation of success in substituting a known sequence of antigen-binding domain into a CAR, this was a well-known substitution at the time of filing and required no more than simple subcloning and routine recombinant technology.
The quantity of experimentation needed to make or use the invention:
Applicant has claimed a genus of any fragment of said IPO13 polypeptide; however, it only describes in the specification amino acid sequence identity 100%. Because Applicant has no manner a priori to predict which amino acid in the IPO13 can be modified and used to make fragments of IPO13 polypeptide, the genus of any fragments claimed by Applicant cannot be predictably made or used by the ordinary artisan. Such random experimentation to identify later what structure, variant, or modification is not functional and is embraced by Applicant's claims is undue experimentation. Furthermore, functionally defined genus claims can be inherently vulnerable to invalidity challenges for lack of written description support, especially in fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
Conclusion:
Taken together, the person of ordinary skill in the art would not have concluded that the applicant possessed the invention as is claimed. The Examiner concludes that there is an insufficient written description of the instantly claimed genus of any fragment of said IPO13 polypeptide. Specifically, it only discloses the amino acid sequence of at least 100% identity SEQ ID Nos: 56-77. However, it claims broadly any fragment of said IPO13 polypeptide. The Examiner further concludes a skilled artisan would find the specification inadequately described.
Claim Rejections - 35 USC § 112(a)
(Scope of Enablement)
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 30 and 36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling the scope for treating a mammal having TDP-43 proteinopathy, wherein said method comprises administering nucleic acid encoding an IPO13 polypeptide, wherein said IPO13 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs: 56-77, does not reasonably provide enablement for any fragment of said IPO13 polypeptide for treating TDP-43 proteinopathy. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
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.'” 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: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
Furthermore, MPEP 2164.03 as set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.).
THE BREADTH OF THE CLAIMS
The breadth of the claims 30 and 36 broadly encompasses the scope to any fragment of said IPO13 polypeptide for treating TDP-43 proteinopathy.
THE NATURE OF THE INVENTION
The nature of the invention is treating a mammal having TDP-43 proteinopathy, wherein said method comprises administering nucleic acid encoding any fragment of IPO13 polypeptide.
THE STATE OF THE PRIOR ART
In the prior art, Zohud et al. (Cell Death and Disease (2020) 11:879; cited in PTO892; hereinafter “Zohud”) teaches a method of IPO13 mediated the nuclear import of RFPL3 through a functional NLS within RFPL3 and subsequent hTERT expression upregulation. Besides, IPO13 was found to play a critical role in NSCLC progression, which was implied by the proliferation promotion of NSCLC cells in vitro and the influence on tumor growth of an NSCLC cancer model in vivo (p. 2 right col. 2nd ¶ of Zohud). Therefore, the prior art does not provide any evidence to support the method comprises administering nucleic acid encoding any fragment of IPO13 polypeptide for treating cancer.
THE LEVEL OF ORDINARY SKILL IN THE ART
An ordinary artisan in the area of cell biology and drug development would have experience of IPO13 polypeptide for treating cancer. Treating cancer using IPO13 polypeptide, while it is complex, is routine in the art. The process of treating using IPO13 polypeptide is well known. Additionally, developing IPO13 with any fragment, as claimed, is generally not well-known or routine, given the complexity of certain biological systems. Thus, the level of ordinary skill in the art of any fragment of said IPO13 polypeptide for treating TDP-43 proteinopathy is high, as an ordinary artisan in this art needs specialized knowledge of the complex nature of the any fragment of IPO13 polypeptide.
THE LEVEL OF PREDICTABILITY IN THE ART
While the treating a mammal having a cancer comprises administering nucleic acid encoding an IPO13 polypeptide is well known, the use of any fragment of PO13 polypeptide to treat TDP-43 proteinopathy within the scope of the claim is not predictable. For instance, Zohud et al. teaches a method of IPO13 mediated nuclear import of RFPL3 through a functional NLS within RFPL3 and subsequent hTERT expression upregulation. Besides, IPO13 was found to play a critical role in NSCLC progression, which was implied by the proliferation promotion of NSCLC cells in vitro and the influence on tumor growth of an NSCLC cancer model in vivo (p. 2 right col. 2nd ¶ of Zohud). Therefore, the prior art does not provide any evidence to support the method comprises administering nucleic acid encoding any fragment of IPO13 polypeptide for treating cancer. Thus, it is unpredictable whether any fragment of IPO13 polypeptide can be used for treating the cancer. The predictability of applying any fragment of amino acid sequence of SEQ ID Nos: 56-77 to treat TDP-43 proteinopathy encompassed by the instant claim would be low given that there doesn’t appear to a link between any fragment of IPO13 polypeptide and the claimed conditions.
THE AMOUNT OF GUIDANCE AND WORKING EXAMPLES DISCUSSION
The specification shows that a subset of β-importins can reduce TDP-CTF aggregates, although importins and exportins interact with Nup62 and other FG-Nups during nuclear transport. IPO13 reduces TDP-CTF aggregation even more strongly that KPNB1 (Figure 19A, 22G). All three exportins strongly associated with Nup62 aggregates, but without affecting their morphology, whereas IPO13 caused strong dissociation and TNPOl partially disassembled TDP-CTF into smaller aggregates (Figure 22G). These results indicate that specific transport receptors have a similar effect on the formation of both TDP-43 and Nup62 aggregates, suggesting a common mechanism (SPEC p. 100 lns 10-20). However, the specification does not provide preferred embodiment that enable to the genus of a nucleic acid sequence encoding any fragment of said IPO13 polypeptide as disclosed in specification and claims 30 and 36. Thus, the specification and the prior art provide sufficient teachings only for amino acid sequence identity to IPO13 or SEQ ID NOs: 56-77.
CONCLUSION
Since both the instant specification and the prior art at the effective filing date of the present application provide a guide to the nucleic acid sequence encoding SEQ ID Nos: 56-77 of said IPO13 polypeptide for treating the TDP-43 of claims 30 and 36 and since does not appear to be any other teaching in the specification and/or prior art that nucleic acid sequence encoding any fragment of said IPO13 polypeptide, it would therefore be unpredictable to practice the invention to any fragment of amino acid sequence of SEQ ID Nos: 56-77 to treat TDP-43 proteinopathy. The prior art provides no compensatory guidance, and since attempts to make any fragment of amino acid sequence of SEQ ID Nos: 56-77 to treat TDP-43 proteinopathy have been unsuccessful. In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims 30 and 36, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention as recited.
Subject Matter Free of Art
According to ABSS report filed Sept. 7, 2026, art does not teach or reasonably suggest the IPO13 polypeptide consists of the amino acid sequence set forth in any one of SEQ ID NOs: 56-77 (see ABSS report filed Sept. 7, 2026).
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic, can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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