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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-5, 16 (partial) and 33 (partial) in the reply filed on 10/30/24 is acknowledged. The traversal is on the ground(s) that by amending the claims unity of invention has been restored. This is not found persuasive because the restriction requirement was based on analysis of the 5/11/22 claim set under review at the time of the Restriction Requirement, and considering these claims the restriction requirement was proper.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8, 9, 12, 14, 15, 20-22, 26, 27, 31, 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/30/24.
Applicant’s 1/9/25 Response electing the species of 10xHis-SUMO1(15-55), a SUMO-derived polypeptide having a 10xHis tag at the N-terminus of the 15-55 segment of SEQ ID NO:1 is acknowledged. This was in response to the Miscellaneous Communication mailed 12/12/24.
The elected species, which was not specifically claimed in the claims, the peptide HHHHHHHHHHDKKEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQ, was found free of the art, and examination proceeded to the claims of Group I.
In accordance with MPEP 803.02 III A, the search was extended to a nonelected species.
This nonelected species is a SUMO-derived polypeptide that comprises the core sequence of SEQ ID NO:1, that is, the 31-55 segment, and a His tag heterologous amino acid sequence at the N-terminus, wherein this polypeptide does not comprise the full length of SEQ ID NO:1.
Applicant’s 8/11/25 claim amendment, as best as understood including based on applicant’s statements and Declaration, does not include the above, first nonelected species in the claimed genus.
Accordingly, the search was extended to a second nonelected species. The second nonelected species is SEQ ID NO:80021 of WO 2017/180587, inventors Barrett et al., published 10/19/2017, (Barrett) which is: KEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQVSL, to which per para 592 of Barrett a polyhistidine tag can be attached.
Claim Status
Claims 1-5, 8, 9, 12, 14-16, 20-22, 26, 27, 31-33 are pending.
Claims 6, 7, 10, 11, 13, 17-19, 23-25, 28-30, 34-37 are cancelled.
Claims 8, 9, 12, 14, 15, 20-22, 26, 27, 31, 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/30/24.
Claims 1-5, 16 (partial) and 33 (partial) are pending and under examination.
Claims 1-5, 16 and 33 are rejected.
Priority
The instant application, filed 09/22/2021 is a National Stage entry of PCT/CN2020/081616 , International Filing Date: 03/27/2020
PCT/CN2020/081616 Claims Priority from Provisional Application 62825560, filed 03/28/2019.
Information Disclosure Statement
As previously set forth, 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, they have not been considered.
Drawings
Applicant’s arguments, see pages 7 and 8, filed 8/11/25, and replacement drawings, with respect to objections to the drawings have been fully considered and are persuasive. The objections to the drawings has been withdrawn.
Nucleotide and/or Amino Acid Sequence Disclosures – Maintained and Modified
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Response to Arguments
Applicant's arguments and amendments to the specification filed 8/11/25 have been fully considered but they are not persuasive. Although applicant has corrected most issues, and provided discussion and a copy of the amended (as to deleting reference to colors) paragraph describing Figure 11, pages 2-3 of Remarks, applicant did not provide SEQ ID Numbers for two of the primers in Table 3, namely the two between those showing “27” and “28” in the following:
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Correction is required.
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 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
See page 60, Table 3, please see above regarding two primer sequences that do not have SEQ ID Numbers. As previously stated, the Sequence Listing must be amended per the rules, which is the basis for the next specific deficiency.
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 sequence identifiers, 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.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in Table 3 at the end, see above.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
Applicant’s arguments, see page 8, file 8/11/25, and specification amendments, with respect to the objection to the specification have been fully considered and are persuasive. The objection to the specification has been withdrawn.
Claim Objections
Applicant’s arguments, see page 8, file 8/11/25, and claim amendments, with respect to the objection to the claim 1 have been fully considered and are persuasive. The objection to claim 1 has been withdrawn.
Claim Interpretation
The claims limitations are given their broadest reasonable interpretation (BRI), (“[T]he ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application.” Phillips v. AWH Corp., 75 USPQ2d 1321, 1326 (Fed. Cir. 2005) (en banc).) The broadest reasonable interpretation of the claims must also be consistent with the interpretation that those skilled in the art would reach.” MPEP 2111, with reference to In re Cortright, 49 USPQ2d 1464, 1468. The claim limitations are given their BRI consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
The transition phrase “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps., see MPEP 2111.03 I. Therefore the claim 1 SUMO-derived polypeptide “comprising” a core sequence encompasses any polypeptide that includes one of the five specified core sequences in claim 1, this a large genus, however excludes any polypeptide that comprises the “full-length” of any of SEQ ID Nos. 1, 3, 4, 5 or 6. “Full-length is interpreted to require the complete amino acid sequence of any of SEQ ID Nos. 1, 3, 4, 5 or 6 without substitutions, additions or deletions of any amino acid of the respective SEQ ID No. 1, 3, 4, 5 or 6.
“Effective amount” in claim 16 is interpreted to mean an amount effective to suppress α-synuclein aggregation in any one or more methods of evaluation for such suppression.
Claim Rejections - 35 USC § 112 - Maintained
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.
Response to Arguments
Applicant's arguments filed 8/11/25 have been fully considered but they are not persuasive.
Applicant argues on pages 8-9 that because the claim 1 SUMO-derived peptide that comprises SEQ ID NO:1, this the 31-55 amino acid segment of a full-length SUMO1 protein, encompasses at a maximum “just 1 amino acid short of full-length SEQ ID NO:1”, so that claim 5 can properly depend from claim 1 and claim 3, “even though the latter further requires a heterologous sequence at the N-terminus,” the rejection should be withdrawn.
This is not persuasive because claim 3 clearly requires a 10xHis tag at the N-terminus of the core sequence (note lines 1-2 of claim 1 state in part “comprising a core sequence, which is the 31-55 segment of SEQ ID NO:1, …” – the 31-55 segment is the only SEQ ID NO:1 core sequence set forth in claim 1, the “is” is not “comprising” nor “including” and the meaning of “is” is unequivocal, the core sequence of SEQ ID NO:1 per claim 1 only can be, per the ordinary and customary meaning of “is”, the 31-55 segment thereof, nothing more, nothing less). So when considering claim 3, and the ordinary and customary meaning of “at” (and the lack of any other reasonable interpretation based on reading the specification, the specification lacking disclosure of linkers or spacers related to this combining), the claim 3 10xHis tag must directly attach to amino acid 31 of the core sequence, 31-55, of SEQ ID NO:1 when the SEQ ID NO:1 core sequence is at issue. As such, given that claim 5 is shown depending from claim 3, and claim 5 is directed to the 15-55 segment of SEQ ID NO:1, there is no possible construct for claim 5’s polypeptide comprising the 15-55 segment of SEQ ID NO:1, because the 10xHis tag introduced by claim 3 interferes with the claim 5 15-55 segment of SEQ ID NO:1 at amino acid 31 of SEQ ID NO:1. Stated another way, claim 5 directed to the polypeptide comprising the 15-55 segment of SEQ ID NO:1 necessarily identifies the relevant core sequence, that being 31-55 of SEQ ID NO:1, but omits an element from claim 3 upon which claim 5 depends, this omitted element being the 10xHis tag attached at amino acid 31 of this core sequence, 31-55, of SEQ ID NO:1 (this core sequence having been identified in claim 5 by selecting the longer 15-55 segment of SEQ ID NO:1). The examiner does not comprehend how the respective limitations of claims 3 and 5 can co-exist as presented in the claim 5 claimed polypeptide (which also of course requires all relevant claim 1 limitations), and given this, is incapable of reasonably interpreting the claim 5 limitation for prior art purposes.
It appears applicant might be confusing core sequence with polypeptide in claim 3 as to where the 10xHis tag attaches at an N-terminus, and/or meaning for claim 5 to depend directly from claim 1, and/or has inadvertently omitted segment 15-55 of SEQ ID NO:1 as a claim 1 core sequence alternative. As claim 5 reads, it impermissibly extends beyond the limitations of claim 3 because per claim 3 there is a 10x His tag attached directly at the N-terminus of any one of the core sequences, and because claim 5 refers to SEQ ID NO:1, there being only one core sequence in claim 1 for SEQ ID NO:1, this 10x His tag attaches at amino acid 31 of that core sequence 31-55 of SEQ ID NO:1, and once this is done such construct does not permit further amino acids, i.e., amino acid 15-30 of SEQ ID NO:1, at the same location.
The examiner hopes that explaining the problem with claim 5 in different ways, above, effectively conveys to the applicant the basis for rejection of claim 5 under this section.
Claim 5 is 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 1 sets forth five core sequences, the only one for SEQ ID NO:1 is the 31-55 segment thereof. Claim 3 further modifies the claim 1 polypeptide, via claim 2, so that a 10xHis tag is at the N-terminus of the core sequence. Claim 5, depending from claim 3, states “comprising the 15-55 segment of SEQ ID NO:1.” This cannot be given that claim 3 already sets forth the 10xHis tag at the N-terminus of the core sequence, which for SEQ ID NO:1 is 31-55, not 15-55. Therefore claim 5 expands beyond the limits of the claim from which it depends, and as such is an improper dependent claim rejected under this section.
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 § 112 – Maintained and Modified
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.
Response to Arguments
Applicant's arguments filed 8/11/25 have been fully considered but they are not persuasive.
Applicant on page 9 argues that the written description is met based on the SUMO-derived polypeptide comprising two parts, a core sequence and one or more heterologous sequences, and “In addition, the SUMO-derived polypeptide is defined by its functionality: it suppresses α-synuclein aggregation without sumoylation of α-synuclein.” This is unpersuasive because the claimed combined functional characteristics – suppressing α-synuclein aggregation, and doing this without sumoylation of α-synuclein, require considering what structure is required to achieve such functional characteristics when considering the entire genus of claim 1 and the structural limitations of claim 1 as a whole.
With regard to comparing the instant application claims to those of In re Herschler, page 10, this is not persuasive because DMSO as a solvent would reasonably enhance delivery of similar steroids, whereas in the instant case there is no near-equivalent-to-In-Re-Herschler similarity among the diverse genus of heterologous amino acid sequences encompassed by claim 1 and the resultant SUMO-derived polypeptides that comprise these. Regardless of the properties of the core, there is no structural limitation that precludes sumoylation of α-synuclein as instantly claimed. Without sufficient claimed structural limitations associated with achieving the claimed overall (combined) functional limitation – of suppressing α-synuclein aggregation without sumoylation of α-synuclein, merely stating that the claimed core sequence is capable of suppressing α-synuclein aggregation without sumoylation of α-synuclein does not satisfy written description because the presence of glycines, including C-terminal diglycines, in the heterologous sequences, as well as beyond the core sequences of the claimed SUMO-derived cores, reasonably can result in sumoylation of α-synuclein, this based on discussion in the 8/11/25 Declaration and the Krumova reference provided with that Declaration, as well as references previously applied in the prior art rejections.
Applicant’s last point on page 10,
that “…the specification provides extensive detailed description of many representative species of the “heterologous amino acid sequences,” including their structural features and the like. This is particularly true considering the required functionality of the claimed SUMO-derived polypeptide—those “heterologous amino acid sequences” resulting in loss of the functionality will be excluded from the claim scope”
is not persuasive because this leaves the task of determining what is encompassed by the claims, and what is to be excluded, to someone other than the applicant, whereas it is the applicant who is responsible for satisfying possession of the claimed genus.
Finally, further to applicant’s arguments against the significance of the heterologous sequences, and not only the size and diversity of the claimed heterologous sequences of claim 1, but to their possible effect (in contrast to the physiologically active steroids advanced as an analogous situation by applicant referring to In re Herschler), Chen et al., Advanced Drug Delivery Reviews 65 (2013) 1357–1369, when teaching the importance of using appropriate linkers when constructing fusion proteins, states on page 1358, “Direct fusion of functional domains without a linker may lead to many undesirable outcomes, including misfolding of the fusion proteins [17], low yield in protein production [18], or impaired bioactivity [19,20].” This further rebuts applicant’s arguments as well as supports the rejection below as to the lack of sufficient support for possession of the claim 1 claimed genus given its size and diversity and the lack of representative species in the application as filed across that genus that retain the claimed functional limitations, i.e., that do not have impaired bioactivity.
Claims 1-5, 16 and 33 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.
Claim 1 is directed to a SUMO-derived polypeptide that:
Comprises a core sequence either 31-55 segment of SEQ ID NO:1, 27-51 segment of SEQ ID NO:3, 26-50 segment of SEQ ID NO:4, 27-51 segment of SEQ ID NO:5, or 31-55 segment of SEQ ID NO:6 (see Figure 8);
One or more heterologous amino acid sequences at the N- and/or C-terminus of the core sequence;
Wherein, in terms of function, “the polypeptide suppresses α-synuclein aggregation without sumoylation of α-synuclein” (underlined limitation added 8/11/25);
With a negative proviso type requirement that “the polypeptide does not comprise the full-length of SEQ ID NO: 1, 3, 4, 5 or 6” (see also Claim Interpretation).
In view of the possible alternatives for the one or more heterologous amino acid sequences at the N- and/or C-terminus of the core sequence, claim 1 encompasses a huge genus of possible amino acid sequences fused to either or both of the N- and C-termini of any of the listed core sequences.
While applicant has demonstrated that core sequences, with or without a His or an Arg tag can suppress α-synuclein aggregation under several experimental conditions, these examples are very limited in their structural diversity and are not representative of the breadth of possible polypeptides of claim 1. Numerous diverse and diversely structured and diversely functioning amino acid sequences can be added to any of these core sequences, and still fall within the scope of claim 1’s SUMO-derived polypeptide based on such polypeptides comprising one of the claim-specified core sequences of the five specified SUMO proteins of SEQ ID Nos: 1 and 3-6, and, further, based on the ‘comprising’ transition additional amino acids of SEQ ID Nos. 1, 3-6 can be present, extending from the core sequence terminus that is not occupied by the heterologous amino acid sequence. The size range of the resultant fused polypeptide is large. Even considering the para 55 statement, “The fusion of one polypeptide (or its coding sequence) with a heterologous polypeptide (or polynucleotide sequence) does not result in a longer polypeptide or polynucleotide sequence that can be found in nature,” based on Linke and Hamdani, Circulation Research, March 14, 2014, 1052-1068, previously provided, the titan protein has 34350 amino acid residues, page 1053, so a polypeptide encompassed by claim 1 can be at least this large. Based on Gotelli et al., Trends in Ecology and Evolution August 2012, Vol. 27, No. 8, pp 436-442, previously provided, the number of diverse proteins is very large, page 438 and elsewhere. Given the diversity of possible heterologous amino acid sequences within the breadth of the claim and this size limit, and given the newly added limitation, there is a lack of teachings, disclosure, and/or structure that provides for function, that would support that the heterologous sequences and/or the entire claimed SUMO-derived polypeptide do not comprise a glycine or di-glycine, which per the 8/11/25 Declaration (notwithstanding that the discussion related to glycines pertained to the references of the prior art rejections) is/are important if not critical to sumoylation.
The small number of polypeptides for which the polypeptide was demonstrated by applicant to suppress α-synuclein aggregation, apparently without sumoylation of α-synuclein, is clearly not representative of the claimed genus, and as such applicant was not in possession of claim 1’s subject matter in its entirety. A point that further supports this conclusion is that even though applicant has shown the importance of one or more of the core sequences in suppressing α-synuclein aggregation in one system or another, applicant has not demonstrated this when a polypeptide comprising one such core sequence also comprises a large, bulky heterologous amino acid sequence that through structure, charge or other factor(s) impedes or prevents the interaction with α-synuclein that would otherwise suppress α-synuclein aggregation, nor as to the newly added functional limitation whether this newly added limitation is met when any heterologous amino acid sequences of the SUMO-derived polypeptide genus comprises a diglycine, nor whether the newly added limitation is met when a SUMO-derived polypeptide that does not comprise the full-length of its corresponding SEQ ID NO. 1, 3, 4, 5 or 6 but does comprise a C-terminus diglycine. Please note that this functional limitation does not have corresponding structural limitations in claim 1 that provide for it to be achieved, which also would limit the breadth of the claimed genus.
The examiner also finds no teachings, structure/function disclosure, nor sufficient examples representative of the claimed genus in the application as filed for the significance of glycines in sumoylation, which per the Declaration of 8/11/25 is relevant to sumoylation, and based on this the examiner concludes that there is a lack of clear support lack as to what is required to not be present in the claimed SUMO-derived polypeptide genus of claim 1 to meet the new limitation of “without sumoylation of α-synuclein” as modifying “wherein the polypeptide suppresses α-synuclein aggregation.”
Accordingly, claim 1 is rejected under this section, as are claims 2 – for which a second heterologous amino acid sequence can be present at the terminus that does not comprise a poly-histidine tag, 3 – where a second heterologous amino acid sequence can be present at the C-terminus that does not comprise the 10xHis tag at the N-terminus, 4 and 5, for the same reason applied to claim 3, and 16 and 33 for the same reasoning applied to claim 1.
Claim Rejections - 35 USC § 102
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.
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.
Response to Arguments and Affidavit
Applicant’s arguments, see page 11, filed 8/11/25, and claim amendments, with respect to the rejection(s) of claim(s) 1 and 2 under 35 USC 102 and/or 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the claim 1 amendment and resultant new search and result thereof.
The examiner has fully considered the Affidavit provided 8/11/25. The applied prior art is no longer what the Affidavit argues against.
Claim(s) 1, 2 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/180587, inventors Barrett et al., published 10/19/2017 (Barrett, provided in two parts, obtained from Espacenet, due to large size).
Claim 1 is directed to a SUMO-derived polypeptide that:
Comprises a core sequence either 31-55 segment of SEQ ID NO:1, 27-51 segment of SEQ ID NO:3, 26-50 segment of SEQ ID NO:4, 27-51 segment of SEQ ID NO:5, or 31-55 segment of SEQ ID NO:6 (see Figure 8);
One or more heterologous amino acid sequences at the N- and/or C-terminus of the core sequence;
Wherein, in terms of function, “the polypeptide suppresses α-synuclein aggregation without sumoylation of α-synuclein” (underlined limitation added 8/11/25);
With a negative proviso type requirement that “the polypeptide does not comprise the full-length of SEQ ID NO: 1, 3, 4, 5 or 6” (see also Claim Interpretation).
For this rejection it is assumed that a diglycine is required for sumoylation, generally and also specifically for sumoylation of α-synuclein. This is consistent with assertions from applicant.
Barrett teaches among its many sequences SEQ ID NO: 80021, which is
Met Ser Asp Gln Glu Ala Lys Pro Ser Thr Glu Asp Leu Gly Asp Lys Lys Glu Gly Glu Tyr Ile Lys Leu Lys Val Ile Gly Gln Asp Ser Ser Glu Ile His Phe Lys Val Lys Met Thr Thr His Leu Lys Lys Leu Lys Glu Ser Tyr Cys Gln Arg Gln Val Ser Leu, which converted to single letter code is MSDQEAKPSTEDLGDKKEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQVSL, a 58 amino acid peptide, and which is listed among numerous payloads of its invention, see paras 99-103.
Comparison of Barrett SEQ ID NO:80021 to instant SEQ ID NO:1 follows:
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Barrett SEQ ID NO:80021 amino acids 1-55 correspond exactly to instant SEQ ID NO:1’s amino acids 1-55, so comprises a core sequence which is the 31-55 segment of instant SEQ ID NO:1. Barrett’s SEQ ID NO:80021 also comprises C-terminus VSL, which is a heterologous amino acid sequence meeting that limitation of instant claim 1 (versus the GVP toward the C-terminus from instant SEQ ID NO:1’s Q at position 55). Based on its size and sequence, Barrett SEQ ID NO:80021 does not comprise the full length of any of instant SEQ ID Nos. 1 or 3-6. Comprising SEQ ID NO:1’s 31-55 amino acids and lacking a diglycine, as best understood for this rejection, the claim 1 functional limitations - “the polypeptide suppresses α-synuclein aggregation without sumoylation of α-synuclein”, are met.
Accordingly, Barrett anticipates claim 1. See MPEP 2131.02 II.
Because Barrett teaches that detectable labels including polyhistidine tags are attached, incorporated or associated with any entity of the invention, and which may be located at any position in the entity with which they are attached, incorporated or associated, and specifically for a peptide or protein, they may be located at the N- or C-termini, para 592, Barrett anticipates claim 2. See MPEP 2131.02 III, stating in part, “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.
Because Barrett teaches its compositions, including comprising SEQ ID NO:80021, to comprise excipients, including pharmaceutically acceptable excipients, see III. Pharmaceutical Compositions paras 335-341, see also paras 655-656 regarding effective amount, Barrett anticipates claim 16. Also see MPEP 2131.02 III.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Response to Arguments and Affidavit
Applicant’s arguments, see pages 11-12, filed 8/11/25, and claim amendments, with respect to the rejection(s) of claim(s) 1 and 2 under 35 U.S.C. 103 as being unpatentable over US 20100048480, inventors Bommarius et al., published 2/25/2010 (“Bomm”) in view of WO 2017/163203 A1, Colnaghi et al., published 9/28/2017 (“Coln”, provided in 12/15/21 IDS so not provided herewith), as evidenced by NCBI NP_003343.1 (NCBI) and Azuma et al., The FASEB Journal express article 10.1096/fj.00-0818fje. Published online June 18, 2001, and the rejection(s) of claims 16 and 33 under 35 U.S.C. 103 as being unpatentable over US 20100048480, inventors Bommarius et al., published 2/25/2010 (“Bomm”) in view of WO 2017/163203 A1, Colnaghi et al., published 9/28/2017 (“Coln”, provided in 12/15/21 IDS so not provided herewith), as evidenced by NCBI NP_003343.1 (NCBI) and Azuma et al., The FASEB Journal express article 10.1096/fj.00-0818fje. Published online June 18, 2001 (“Azuma”, provided with 4/10/24 IDS so not provided herewith), as applied to claim 1, and further in view of Mohan, Buffers, Calbiochem, 2003, 37 pages (Mohan), and Omar et al., J Med Food 17 (5) 2014, 588–598 (Omar) have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the claim 1 amendment and resultant new search and result(s) thereof.
The examiner has fully considered the Affidavit provided 8/11/25. The applied prior art is no longer what the Affidavit argues against.
Claim(s) 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/180587, inventors Barrett et al., published 10/19/2017 (Barrett, provided in two parts, obtained from Espacenet, due to large size), in view of Kimple et al., 2015, Curr Protoc Protein Sci. ; 73: Unit–9.9 (Kimple).
Claims 1 and 2 are rejected as anticipated above.
As to claim 3, Barrett does not explicitly teach a 10xHis tag.
Kimple teaches that his tags are commonly used as affinity tags, and although usually consisting of six histidines, “can vary in length from two to ten histidine residues,” page 2.
Because a ten histidine his tag is common and known in the art per Kimple, and given that Barrett already teaches combining its components with polyhistidine tags, it would have been obvious to select one of the known sizes of histidine tags because these are within the commonly used range for his tags.
Therefore one or ordinary skill in the art would have reasonably selected this size, this in a small range specifically taught by Kimple and at the large size end of this range, because when considering his tags following the teachings of Barrett regarding the same this size per Kimple was being routinely used so would expected to be effective, and there would have been a reasonable expectation of success given the clear teachings of Kimple, and accordingly claim 3 would have been obvious.
Claim 4 would have been obvious because this core sequence already has been rejected above when rejecting claim 1.
Claim(s) 33 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/180587, inventors Barrett et al., published 10/19/2017 (Barrett, provided in two parts, obtained from Espacenet, due to large size).
Claim 1 is rejected as anticipated above.
Because Barrett teaches its compositions to be directed to treating various neurological diseases, para 408, and teaches kits, paras 479-482, and to include provision of neuropeptides, para 533, the preparation of a kit comprising a first container (see para 467) containing (interpreted as comprising, so can include SEQ ID NO:80021 alone, combined with other components, as well as joined chemically to one or more other components), and a second container containing a neuroprotective agent, these abundantly taught in Barrett, would reasonably have been one of many type of kits envisioned by one of ordinary skill in the art reading Barrett, based on its inclusion of methods of treating various neurological diseases, and therefore claim 33 would have been obvious. There would have been a reasonable expectation of success at least in view of the nature of the claim (given that this claim is directed to a kit, the “for treating a neurodegenerative disease”, is merely preamble intended use, see MPEP 2112.02, stating in part, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”)
Accordingly, claim 33 is rejected as obvious.
Conclusion
No claim is 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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/JOSEPH FISCHER/Examiner, Art Unit 1658