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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
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 drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, no sequence identification has been provided for the sequence presented in Figure 6 dated 04/01/2024.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant's election with traverse of Group I (claims 1-15), SEQ ID NO:6 where serine 28 is glycosylated by melibiose in the reply filed on July 20, 2026 is acknowledged. The traversal is on the ground(s) that searching all the claims will not result in serious burden for the examiner. This is not found persuasive because an application may properly be required to be restricted to one of two or more claimed inventions if they are able to support separate patents and they are either independent (MPEP § 806.04 - § 806.04 (j)) or distinct (MPEP § 806.05 - § 806.05 (i)). The Examiner has shown that the Groups I and II are independent or distinct for the reasons in the previous Office action (see Paper mailed on May 20, 2026). Furthermore, MPEP § 803 provides that the separate classification (i.e., class and subclass) of distinct inventions is sufficient to establish a prima facie case that the search and examination of the plural inventions would impose a serious burden upon the Examiner; such separate classification was set forth in the Office action mailed May 20, 2026.
In addition, as previously made of record, the examiner has required restriction between product and process claims. Where applicant elects claims directed to the product, and the product claims are subsequently found allowable, withdrawn process claims that depend from or otherwise require all the limitations of the allowable product claim will be considered for rejoinder. In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product are found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product claim will not be rejoined. See MPEP § 821.04(b). Additionally, in order to retain the right to rejoinder in accordance with the above policy, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product claims. Failure to do so may result in a loss of the right to rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
The requirement is still deemed proper and is therefore made FINAL.
4. Claims 1-18 are pending in this application. Claims 16-18 are withdrawn with traverse (filed 07/20/2026) 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. Upon reconsideration, the species election between SEQ ID NOs: 6 and 7 is withdrawn. Thus, the subject matter to the extent of SEQ ID NO: 2 will be included and under examination in this office action. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/11/19.
5. Claims 1-15 are under examination with respect to SEQ ID NO:6 where serine 28 is glycosylated by melibiose in this office action.
Priority
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. 15/044924, PCT/US14/051143 and provisional Application No. 61/865958, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The instant application claims a glycopeptide comprising a polypeptide and one or more saccharide moieties covalently linked to the polypeptide, wherein the glycopeptide is capable of crossing human blood brain barrier (BBB) and having a sequence of SEQ ID NO:5 with specific residues at positions 4, 5, 7, 17, 26, 27 and 28 and at least one amino acid residue is glycosylated as recited in independent claim 1. The clamed glycopeptide with different combinations of variants in X4 (glycine/alanine/D-alanine/sarcosine/b-analine/daminovaleric acid), X5 (isoleucine/valine/leucine/L-tert-Leucine/L-nor-Valine/L-Nor-Leucine/glycine/sarcosine/D or L-alanine/D or L-N-methylalanine) and X7 (alanine) of SEQ ID NO:5 recited in claim 1 is not presented in the Application No. 15/044924 filed 2/16/16, PCT/US14/051143 filed 8/14/14 and provisional Application No. 61/865958 filed 8/14/13. The claimed glycopeptide with different combinations of X4, X5 and X7 was only disclosed in the instant Application 16181129 filed on Nov 5, 2018 (see paragraph [0070], table 1 of the specification). The priority of the glycopeptide: 1-HsDGIFTDSYSRYRKQLAVKKYLAAVLS*-28 was disclosed in provisional Application No. 61/865958 filed Aug 14, 2013.
Therefore, the priority for the glycopeptide: 1-HsDGIFTDSYSRYRKQLAVKKYLAAVLS*-28 is Aug 14, 2013. The priority for the claimed glycopeptide with different combinations of variants in X4, X5 and X7 of SEQ ID NO:5 recited in claim 1 of instant application is Nov 5, 2018.
Drawings
7. The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the sequence identifiers in Figure 6 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
8. Claims 16-18 are objected to because of the following informalities: the status of claims 16-18 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claim Rejections - 35 USC § 112
9. 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 8-12 and 15 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 pre-AIA the applicant regards as the invention.
Claims 8-12 and 15 are indefinite because it is unclear whether the limitation “the glycopeptide” and the limitation “said glycopeptide” recited in claims 8-12 and 15 refers to the same glycopeptide. Thus, the claims are indefinite.
Claim Rejections - 35 USC § 112
10. 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 1-15 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-15 encompass a genus of glycopeptide comprising a polypeptide and one or more saccharide moieties covalently linked to the polypeptide, wherein the glycopeptide is capable of crossing blood brain barrier (BBB), and has a sequence of HS*DX4X5FX7DS*YS*RYRKQX17AVKKYLAAX26X27X28 (SEQ ID NO:5) wherein *: D/L-isomer; X4: Gly,Ala, D-Ala, Sar, b-Ala or diaminovaleric acid; X5: ILeu, Val, Leu, L-tert-Leu, L-nor-Val, L-Nor-Leu, Gly, Sar, D/L-Ala, D/L-N-Methyl-Ala; X7: Thr or Ala; X17: Met or L-Nor-Leu; X26: Val or Leu; X27: Leu or Ser and X28: absent or Ser and wherein at least one amino acid residue of the polypeptide is glycosylated.
Claims 8-10 and 11-12 encompass a genus of the claimed glycopeptide that is a PAC1 agonist or/and VPAC1 agonist or with PAC1/VPAC1 binding affinity (Ki) of less than about 10nM.
Claim 15 encompasses a genus of the claimed glycopeptide that is capable of penetrating BBB and reaching a CSF concentration of at least 50nM, 100nM or 400nM 60 minutes after being injected into a subject intravenously at a concentration of 15mg glycopeptide per kg/body weight of the subject.
Applicant has not disclosed sufficient species for the broad genus of glycopeptide comprising a polypeptide and one or more saccharide moieties covalently linked to the polypeptide, wherein the polypeptide has a sequence of SEQ ID NO:5 and with the recited residues for X4, X5, X7, X17, X26, X27 and X28 and wherein at least one amino acid residue of the polypeptide is glycosylated or having specific activity including specific PAC1 binding affinity or agonist activity with specific binding affinity or capable of crossing the BBB and reaching a specific CSF concentration.
The specification only disclosed that glycopeptides of SEQ ID NO:5 modified as shown in SEQ ID NOs: 2 and 9-11 can act as PAC1/VPAC1/2 agonist and function as PACAP-27 (SEQ ID NO:2) or PACAP-38 (SEQ ID NO:1) (see paragraph [0099], table 2) but not SEQ ID NOs: 12-15 or other glycopeptides shown in table 1.
The specification only discloses that D82LS98Lact glycopeptide can cross the BBB (Figures 7A-B), glycopeptides 2LS80Mel (SEQ ID NO:6-Ser-Mel) for TBI (attenuated motor skill and cognitive deficits induced by TBI) and 2LS98Lac (SEQ ID NO:7-Ser-Lac) for PD (Figures 8-9). The specification disclosed that 2LS80Mel (SEQ ID NO:6-Ser-Mel) attenuated motor skill and cognitive deficits induced by TBI but no difference in inflammatory cytokines and microglial morphology (see p. 38-39,[0149]-[0151]). The specification disclosed that 2LS98Lac (SEQ ID NO:7-Ser-Lac) rescues 6-OHDA induced morphological changes to microglia but no changes in striatal TH expression or striatal dopaminergic content or 6-OHDA-induced lesion damage (p. 9 [0058]; p. 39-40, [0152]-[0154]).
However, the claims are not limited to the glycopeptide of SEQ ID NO: 2 or 9-11 or SEQ ID NO:6-Ser-Mel or SEQ ID NO:7-Ser-Lac set forth above but also encompass structurally and functionally undefined glycopeptide variants. The specification provides no other structural and functional relationship between other glycopeptides shown in table 1 and SEQ ID NOs: 2 and 9-11 or SEQ ID NO:6-Ser-Mel or SEQ ID NO:7-Ser-Lac.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of glycopeptide of SEQ ID NO:2 with a specific modification as shown SEQ ID NOs: 9-11 in table 2 to act as PAC1 agonist, or VPAC1 or VPAC2 agonist (paragraph [0074], table 2) or 2LS80Mel (SEQ ID NO:6-Ser-Mel) for attenuating motor skill and cognitive deficits induced by TBI or 2LS98Lac (SEQ ID NO:7-Ser-Lac) for crossing the BBB or recusing 6-OHDA induced morphological changes to microglia. However, Applicant is not in possession of other structurally and functionally undefined glycopeptides having a sequence of SEQ ID NO:5 covalently linked to one or more saccharide moieties at any position.
The limitation “a sequence of SEQ ID NO:5” also encompasses fragments within SEQ ID NO:5.
Based on Applicant’s own admission in table 2 of the specification, a single amino acid modification changes the activity of the glycopeptide of SEQ ID NO:2 or SEQ ID NO:1 (PACAP-38) or SEQ ID NO:2 (PACAP-27); for example SEQ ID NO ID NOs: 12-15 (see table 2 of the specification). The glycopeptide of SEQ ID NOs: 12-15 have either an opposite effect to SEQ ID NO:2 or no activity (see p. 20, paragraph [0099], table 2).
SEQ ID NO:5 1 HSDX4X5FX7DSYSRYRKQX17AVKKYLAAX26X27X28 28
SEQ ID NO:6 1 HSDG4I5FT7DSYSRYRKQL17AVKKYLAAV26L27S28 28
SEQ ID NO:7 1 HSDG4I5FT7DSYSRYRKQL17AVKKYLAAV26L27S28 28
SEQ ID NO:4 1 H**S*DX4X5FX7DS*YS*RYRKQX17AVKKYLAAX26X27X28 28
PACAP1-38(SEQ ID NO:1) 1 H**S*DG4I5FT7DS*YS*RYRKQM17AVKKYLAAV26L27GKRYKQRVKNK 38
PACAP1-27(SEQ ID NO:2) 1 H**S*DG4I5FT7DS*YS*RYRKQM17AVKKYLAAV26L27 27
Table 2
SEQ ID NO:2(PACAP1-27)(100) 1 HSDGIFTDSYSRYRKQMAVKKYLAAVL 27
SEQ ID NO:9(99) 1 HSDGIFTDSYSRYRKQLAVKKYLAAVLS(Mel) 28
SEQ ID NO:10(85) 1 HsDGIFTDSYSRYRKQNAVKKYLAAVLS(Glc) 28
SEQ ID NO:11(86) 1 HsDGIFTDSYSRYRKQNAVKKYLAAV-S(Glc) 27
SEQ ID NO:12(-79) 1 HsDGIFADSYSRYRKQNAVKKYLAA-LS(Glc)L 27
SEQ ID NO:13(-71) 1 HsDGIFADSYSRYRKQNAVKKYLAAVLS(Glc) 28
SEQ ID NO:14(NC) 1 HsDGIFADSYSRYRKQNAVKKYLAAV-S(Glc) 27
SEQ ID NO:15(NC) 1 HsDGIFADSYSRYRKQNAVKKYLAAV-S(Glc)L 28
[AC-His1]PACAP1-27 1 HSDGIFTDSYSRYRKQMAVKKYLAAVL 27
While the instant claims recite the glycopeptides listed in tables 1-2, the specification fails to demonstrate that Applicant is in possession of the claimed glycopeptides that has the activity as PACAP or described in paragraphs [0045]-[0046] or is a PAC1 agonist or PAC1 and VPAC1 agonist or with PAC1 binding affinity/ agonist activity of less than about 10nM as recited in instant claims 8-12 because what other common characteristics/features of the glycopeptides are unknown.
The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed genus of glycopeptides in order to preserve the activity of SEQ ID NO:1 or 2 to act as PACAP27/38 or PAC1 agonist or PAC1 and VPAC1 agonist or with PAC1 binding affinity/ agonist activity of less than about 10nM because a single amino acid modification on a peptide/polypeptide can change or abolish the activity or binding ability of the peptide/polypeptide as evidenced by Burgess et al. (J of Cell Bio. 1990, 111:2129-2138), Pawson et al. (Science, 2003; 300:445-452). For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138, as in IDS). Although many amino acid substitutions are possible in any given protein, the position of where such amino acid substitutions can be made is critical for maintaining the function of a protein; i.e. only certain positions can tolerate conservative substitutions without changing the relationship of three dimensional structure and function of the protein (col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310, as in IDS). Although the specification outlines art-recognized procedures for producing and the screening method, this is not adequate guidance as to the nature of active glycopeptides and variants thereof for PAC1 agonists that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. Further, even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452, as in IDS). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452, as in IDS). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507, as in IDS). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210,as in IDS).
Applicant fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed genus of glycopeptide variants in order to preserve the activity of SEQ ID NO:1 or 2 to act as PAC1 agonists. There is no description of the conserved regions which are critical to the function of the claimed genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of the structure of other glycopeptides or variants thereof to the function of SEQ ID NOs: 1-2 or sequences listed in table 2. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other structurally and functionally undefined glycopeptides might be. Since the common characteristics/features of other structurally and functionally undefined glycopeptides are unknown, a skilled artisan cannot envision the functional correlations of the claimed genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of glycopeptides.
The specification fails to provide sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. There is no description of the conserved regions which are critical to the function of the claimed genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of the structure of other glycopeptides or variants thereof to the function of SEQ ID NOs: 1-2 or sequences listed in table 2. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other structurally and functionally undefined glycopeptides might be. Since the common characteristics/features of other structurally and functionally undefined glycopeptides are unknown, a skilled artisan cannot envision the functional correlations of the claimed genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of glycopeptides.
Based on MPEP § 2161.01 and §2163, “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”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of glycopeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed glycopeptides have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
11. 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 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.
Claim Rejections - 35 USC § 102
12. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5-6 and 8-15 are rejected under 35 U.S.C. 102(a)(1) &(a)(2) as being anticipated by Coy et al. (US2012/030968, published Dec 6, 2012, priority Feb 5, 2010) as evidenced by Sola et al. (see p. 3-5, protein glycosylation. BioDrugs, 2010; 24:9-21).
Claims 1-2, 5-6 and 8-15 are drawn to a glycopeptide comprising a polypeptide and one or more saccharide moieties covalently linked to the polypeptide, wherein the glycopeptide is capable of crossing blood brain barrier (BBB) and have a sequence of HSDX4X5FX7DSYSRYRKQX17AVKKYLAAX26X27X28 (SEQ ID NO:5) with at least one amino acid residue that is glycosylated;
X4: Gly,Ala, D-Ala, Sar, b-Ala or diaminovaleric acid;
X5: ILeu, Val, Leu, L-tert-Leu, L-nor-Val, L-Nor-Leu, Gly, Sar, D/L-Ala, D/L-N-Methyl-Ala;
X7: Thr or Ala;
X17: L-Nor-Leu; Val; Nor-Val; Ala or another aliphatic amino acid or Gly;
X26: Val or Leu;
X27: Leu or Ser and
X28: absent or Ser.
Dependent claims are directed to Serine at 2-position is (D)-isomer (claim 2), a PAC1 agonist and/or a VPAC1 agonist (claims 8-10), PAC1/VPAC1 binding affinity (Ki) is less than about 10nM (claims 11-12), comprising more than one glycosylated amino acid residue (claim 13), wherein the saccharide include glucose, maltose, lactose, melibiose….polysaccharides related to Thompsen-Friedrich antigens (Tn) (claim 14), wherein the glycopeptide is capable of penetrating the BBB and reaching a CSF concentration of at least 50nM or 100nM or 400nM 60 min after being injected into a subject intravenously at a concentration of 15mg glycopeptide/kg body weight of the subject (claim 15).
Coy et al. (US2012/030968) teach a glycopeptide of PACAP27 comprising a polypeptide of SEQ ID NO: 41 ([D-Ser2,Nle17]PACAP27) or SEQ ID NO:51 ([D-Ser2,Nle17, D-Leu27]PACAP27), which is identical to the claimed glycopeptide of instant SEQ ID NO:5, wherein X4 is G, X5 is I, X7 is T, X26 is V, X27 is L and X28 is absent, and wherein Serine at position 2 is D-isomer and wherein at least one amino acid residue is glycosylated, and thus meets the limitations recited in instant claims 1-2, 5-6 and 8-15 (see the sequence alignment below; para. [0169]). Coy teaches that the glycosylated PACAP27 comprises more than one glycosylated amino acid residue (see para. [0169]). The glycosylated PACAP27 disclosed by Coy inherently possesses one carbohydrate or saccharide as recited in instant claim 1 as evidenced by Sola et al. (see p. 3-5, protein glycosylation. BioDrugs, 2010; 24:9-21).
Coy also teaches the limitations recited in instant claims 8-12 and 14-15 because the glycopeptide disclosed by Coy is identical to the claimed glycopeptide and thus possesses the features recited in claims 8-12 and 14-15. Note that
“Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection. ‘There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102.’ In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA1977).” See MPEP § 2112.
Thus, claims 1-2, 5-6 and 8-15 are anticipated by Coy et al. (US2012/030968) as evidenced by Sola.
The sequence search results disclose as follows:
SEQ ID NO:6
US-13-577-132-41
; Sequence 41, Application US/13577132
; Publication No. US20120309683A1
; GENERAL INFORMATION
; APPLICANT: COY, David H.
; APPLICANT:MADERDRUT, Jerome L.
; APPLICANT:LI, Min
; APPLICANT:BATUMAN, Vecihi
; TITLE OF INVENTION: THE USE OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE
; TITLE OF INVENTION:(PACAP) AND PACAP ANALOGS AS ADJUNCTIVE TREATMENTS WITH
; TITLE OF INVENTION:INHIBITORS OF CALCINEURIN OR INHIBITORS OF THE MAMMALIAN TARGET
; TITLE OF INVENTION:OF RAPAMYCIN (MTOR) COMPLEXES
; FILE REFERENCE: 07005/013002
; CURRENT APPLICATION NUMBER: US/13/577,132
; CURRENT FILING DATE: 2012-08-03
; PRIOR APPLICATION NUMBER: PCT/US2011/023930
; PRIOR FILING DATE: 2011-02-07
; PRIOR APPLICATION NUMBER: 61/337,679
; PRIOR FILING DATE: 2010-02-05
; NUMBER OF SEQ ID NOS: 72
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 41
; LENGTH: 27
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Description of Artificial Sequence: Synthetic
; OTHER INFORMATION:peptide
; FEATURE:
; NAME/KEY: MOD_RES
; LOCATION: (2)..(2)
; OTHER INFORMATION: D-Ser
; FEATURE:
; NAME/KEY: MOD_RES
; LOCATION: (17)..(17)
; OTHER INFORMATION: Nle
; FEATURE:
; OTHER INFORMATION: C-term amidated
US-13-577-132-41
Query Match 97.1%; Score 136; DB 10; Length 27;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
|||||||||||||||||||||||||||
Db 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
Sequence 51, US/13577132
Publication No. US20120309683A1
GENERAL INFORMATION
APPLICANT: COY, David H.
APPLICANT: MADERDRUT, Jerome L.
APPLICANT: LI, Min
APPLICANT: BATUMAN, Vecihi
TITLE OF INVENTION: THE USE OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE
TITLE OF INVENTION: (PACAP) AND PACAP ANALOGS AS ADJUNCTIVE TREATMENTS WITH
TITLE OF INVENTION: INHIBITORS OF CALCINEURIN OR INHIBITORS OF THE MAMMALIAN TARGET
TITLE OF INVENTION: OF RAPAMYCIN (MTOR) COMPLEXES
FILE REFERENCE: 07005/013002
CURRENT APPLICATION NUMBER: US/13/577,132
CURRENT FILING DATE: 2012-08-03
PRIOR APPLICATION NUMBER: PCT/US2011/023930
PRIOR FILING DATE: 2011-02-07
PRIOR APPLICATION NUMBER: 61/337,679
PRIOR FILING DATE: 2010-02-05
NUMBER OF SEQ ID NOS: 72
SEQ ID NO 51
LENGTH: 27
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
peptide
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (2)..(2)
OTHER INFORMATION: D-Ser
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (17)..(17)
OTHER INFORMATION: Nle
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (27)..(27)
OTHER INFORMATION: D-Leu
FEATURE:
OTHER INFORMATION: C-term amidated
Query Match 97.1%; Score 136; DB 10; Length 27;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
|||||||||||||||||||||||||||
Db 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
US-13-577-132-15
Sequence 15, US/13577132
Publication No. US20120309683A1
GENERAL INFORMATION
APPLICANT: COY, David H.
APPLICANT: MADERDRUT, Jerome L.
APPLICANT: LI, Min
APPLICANT: BATUMAN, Vecihi
TITLE OF INVENTION: THE USE OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE
TITLE OF INVENTION: (PACAP) AND PACAP ANALOGS AS ADJUNCTIVE TREATMENTS WITH
TITLE OF INVENTION: INHIBITORS OF CALCINEURIN OR INHIBITORS OF THE MAMMALIAN TARGET
TITLE OF INVENTION: OF RAPAMYCIN (MTOR) COMPLEXES
FILE REFERENCE: 07005/013002
CURRENT APPLICATION NUMBER: US/13/577,132
CURRENT FILING DATE: 2012-08-03
PRIOR APPLICATION NUMBER: PCT/US2011/023930
PRIOR FILING DATE: 2011-02-07
PRIOR APPLICATION NUMBER: 61/337,679
PRIOR FILING DATE: 2010-02-05
NUMBER OF SEQ ID NOS: 72
SEQ ID NO 15
LENGTH: 38
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (2)..(2)
OTHER INFORMATION: D-Ser
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (17)..(17)
OTHER INFORMATION: Nle
FEATURE:
OTHER INFORMATION: C-term amidated
Query Match 97.1%; Score 136; Length 38;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
|||||||||||||||||||||||||||
Db 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
Claim Rejections - 35 USC § 103
13. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Coy et al. (US2012/0309683) in view of Shandler (US2013/0096050, published Apr 18, 2013, priority Apr 22, 2010) and Polt et al. (US7803764, issued Sep 28, 2010).
Coy is set forth above but does not teach that X28 is Serine, glycosylated with glucose, galactose, melibiose, xylose, lactose, trehalose, or altose as in claims 3-4.
Shandler (US2013/0096050) teaches a composition comprising a PACAP-27 analog with one more amino acid substitutions and including glycosylated analogs (see paragraphs [0003]; [0027]-[0038]; [0040]-[0041]; [0043]-[[0050]; [0160], table 1; [0186]-[0187]; [0293], table 4; [0857], claim 65; in particular) or a VIP analog (see [0293],); wherein the PACAP analog or VIP analog is an agonist of PAC1 (see p. 43, [0300], [0316]-[0590], in particular). Shandler also teaches that the C-terminus end is glycosylated or a plurality of glycosylated amino acids (see [0044]-[0045]; [0186]-[0190]; [0300], in particular). Shandler teaches that the glycopeptide is a PAC1 agonist with binding affinity/agonist activity less than about 10nM as in claims 8-10 (see [0230], [0293], [0316]-[0590], in particular) and that the saccharide including lactose as in claim 4 (see [0186]-[0187], in particular).
Polt (US7803764) teaches that glycosylation of therapeutic proteins at the C-terminus (position 27 of PACAP-27) and glycosylation at serine residue as in claims 3-4 helps stabilization of protein drugs, penetration of BBB, and thus improves therapeutic efficacy of the proteins (see abstract; Col. 7, lines 45-55; col. 5, line 22-col.7, line 6, in particular). Polt teaches glycosylation with at least one saccharide moeity including beta-D-glucose, beta-maltose, beta-lactose, beta-meilibiose, beta-maltotriose, sucrose, trehalose, sacchariose, maltose, cellobiose, gentibiose, isomaltose, primeveose…as in claim 4 (see col.7, line 26-64, in particular).
A person of ordinary skill in the art would have recognized that selecting and applying the known glycosylated Serine at the C-terminus of PACAP-27 or glycosylated PACAP-27: [D-Ser2,Nle17]PACAP27 or [D-Ser2,Nle17, D-Leu27]PACAP27 and the known technique disclosed by Shandler and Polt to the Coy’s glycosylated PACAP-27 would have yielded the predictable result of the claimed glycopeptide comprising SEQ ID NO:5, or 6, 6 wherein glycosylated Serine at position X28 of SEQ ID NO:5, and resulted in an improved product because glycosylation of therapeutic proteins at the C-terminus end of PACAP-27 by a glycosylated Serine improves therapeutic efficacy of the proteins and crossing the BBB, and glycosylation at serine residue has been successfully used to generate such glycosylated therapeutic proteins for better therapeutic efficacy as taught by Polt.
Modifying the C-terminus of glycosylated PACAP-27: [D-Ser2,Nle17]PACAP27 or [D-Ser2,Nle17, D-Leu27]PACAP27 by adding a glycosylated Serine to the Choys’ glycosylated PACAP-27: [D-Ser2,Nle17]PACAP27 or [D-Ser2,Nle17, D-Leu27]PACAP27 would generate the claimed glycopeptide, and help stabilization of glycosylated PACAP and penetration of BBB, and thus improve therapeutic efficacy of the glycosylated PACAP proteins, and would expand application of the Coy’s glycosylation and increase patient’s satisfaction with treatment using glycosylated PACAP.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known glycosylated Serine at the C-terminus of PACAP-27 or glycosylated PACAP-27: [D-Ser2,Nle17]PACAP27 or [D-Ser2,Nle17, D-Leu27]PACAP27 and the known technique disclosed by Shandler and Polt to the Coy’s glycosylated PACAP-27, and yield the predictable result of the claimed glycopeptide with a glycosylated Serine at position X28 of SEQ ID NO:28 for better stabilization and penetration of BBB for the glycosylated PACAP.
Conclusion
14. NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:5 1 HSDXXFXDSYSRYRKQXAVKKYLAAXXX 28
SEQ ID NO:6 1 HSDGIFTDSYSRYRKQLAVKKYLAAVLS 28
PACAP1-27 1 HSDGIFTDSYSRYRKQMAVKKYLAAVL
PACAP1-27-S-G 1 HSDGIFTDSYSRYRKQMAVKKYLAAVS-O-b-D-Glc 27
15. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US5623050 teaches a peptide comprising the amino acid sequence of SEQ ID NO:5, which is 97.1% identical to instant SEQ ID NO:6 (see the sequence alignment below).
SEQ ID NO:6
US-07-932-455A-5
; Sequence 5, Application US/07932455A
; Patent No. 5623050
; GENERAL INFORMATION:
; APPLICANT: KITADA, Chieko
; APPLICANT: WATANABE, Takuya
; TITLE OF INVENTION: STABLE POLYPEPTIDES HAVING cAMP PRODUCTION
; TITLE OF INVENTION: ENHANCING ACTIVITY AND THE USE THEREOF
; NUMBER OF SEQUENCES: 27
; CORRESPONDENCE ADDRESS:
; ADDRESSEE: DAVID G. CONLIN; DIKE, BRONSTEIN, ROBERTS &
; ADDRESSEE: CUSHMAN
; STREET: 130 Water Street
; CITY: Boston
; STATE: Massachusetts
; COUNTRY: US
; ZIP: 02109
; COMPUTER READABLE FORM:
; MEDIUM TYPE: Floppy disk
; COMPUTER: IBM PC compatible
; OPERATING SYSTEM: PC-DOS/MS-DOS
; SOFTWARE: PatentIn Release #1.0, Version #1.25
; CURRENT APPLICATION DATA:
; APPLICATION NUMBER: US/07/932,455A
; FILING DATE: 18-AUG-1992
; CLASSIFICATION: 530
; ATTORNEY/AGENT INFORMATION:
; NAME: CONLIN, David G
; REGISTRATION NUMBER: 27026
; TELECOMMUNICATION INFORMATION:
; TELEPHONE: (617)523-3400
; TELEFAX: (617)523-6440
; TELEX: 200291 STRE UR
; INFORMATION FOR SEQ ID NO: 5:
; SEQUENCE CHARACTERISTICS:
; LENGTH: 27 amino acids
; TYPE: amino acid
; TOPOLOGY: linear
; MOLECULE TYPE: protein
US-07-932-455A-5
Query Match 97.1%; Score 136; DB 3; Length 27;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
|||||||||||||||||||||||||||
Db 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
US5801147 teaches a peptide comprising the amino acid sequence of SEQ ID NO:5, which is 97.1% identical to instant SEQ ID NO:6 (see the sequence alignment below).
SEQ ID NO:6
US-08-766-725A-5
; Sequence 5, Application US/08766725A
; Patent No. 5801147
; GENERAL INFORMATION:
; APPLICANT: Kitada, Chieko
; APPLICANT: Watanabe, Takuya
; TITLE OF INVENTION: POLYPEPTIDES AND USE THEREOF
; NUMBER OF SEQUENCES: 27
; CORRESPONDENCE ADDRESS:
; ADDRESSEE: Dike, Bronstein, Roberts & Cushman, LLP
; STREET: 130 Water Street
; CITY: Boston
; STATE: MA
; COUNTRY: USA
; ZIP: 02109
; COMPUTER READABLE FORM:
; MEDIUM TYPE: Diskette
; COMPUTER: IBM Compatible
; OPERATING SYSTEM: DOS
; SOFTWARE: FastSEQ for Windows Version 2.0
; CURRENT APPLICATION DATA:
; APPLICATION NUMBER: US/08/766,725A
; FILING DATE: 13-DEC-1996
; CLASSIFICATION: 514
; PRIOR APPLICATION DATA:
; APPLICATION NUMBER: 07/932,455
; FILING DATE: 18-AUG-1992
; ATTORNEY/AGENT INFORMATION:
; NAME: Conlin, David G.
; REGISTRATION NUMBER: 27,026
; REFERENCE/DOCKET NUMBER: 42060-C
; TELECOMMUNICATION INFORMATION:
; TELEPHONE: 617-523-3400
; TELEFAX: 617-523-6440
; TELEX:
; INFORMATION FOR SEQ ID NO: 5:
; SEQUENCE CHARACTERISTICS:
; LENGTH: 27 amino acids
; TYPE: amino acid
; STRANDEDNESS: single
; TOPOLOGY: linear
; MOLECULE TYPE: protein
US-08-766-725A-5
Query Match 97.1%; Score 136; DB 3; Length 27;
Best Local Similarity 100.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
|||||||||||||||||||||||||||
Db 1 HSDGIFTDSYSRYRKQLAVKKYLAAVL 27
16. Any inquiry of a general nature or relating to the status of this general application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Papers relating to this application may be submitted to Technology Center 1600, Group 1649 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15, 1989). Should applicant wish to FAX a response, the current FAX number for Group 1600 is (571) 273-8300.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chang-Yu Wang whose telephone number is (571) 272-4521. The examiner can normally be reached on Monday-Thursday from 7:00 AM to 5:30 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeffrey Stucker, can be reached at (571) 272-0911.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Chang-Yu Wang
September 19, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights