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 .
Claims 1-16 are pending and under examination in the instant application.
Priority
The instant application, filed 08/08/2024 is a CON of 17/259,508 (filed 01/11/2021), which is a national stage entry under 35 USC 371 of PCT/US2019/041852 (filed 07/15/2019), which claims priority to US Provisional Application 62/698,576 (filed 07/16/2018). Thus, the earliest possible effective filing date is 07/16/2018.
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 - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825. This application contains a “Sequence Listing” as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)). A copy of the "Sequence Listing" in computer readable form (CRF) has been submitted; however, the content of the CRF does not comply with one or more of the requirements of 37 CFR 1.822 through 1.824, as indicated in the "Error Report" that indicates the "Sequence Listing" could not be accepted. Refer to attachment or document "Computer Readable Form (CRF) for Sequence Listing – Defective" dated 08/08/2024.
Required response – Applicant must provide:
A replacement "Sequence Listing" part of the disclosure, as described above in item 1); together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 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 replacement "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 and
An amendment to the specification to remove the “Sequence Listing previously submitted as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3))
If the replacement "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, Applicant must also provide:
A CRF in accordance with 1.821(e)(1) or 1.821(e)(2) as required by 37 CFR 1.825(b)(6)(ii); and
Statement according to item 2) a) or b) above.
Furthermore,
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.
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.
In the instant case, FIG. 8 contains a disclosure of enumerated amino acid sequences that are not contained in the Sequence Listing or CRF.
Claim Objections
Claims 2-3 and 12-13 are objected to because of the following informalities:
Claim 2 recites “A Wnt signaling agonist comprising a polypeptide of claim 1…”. It should read as “A Wnt signaling agonist comprising the Wnt signaling antagonist polypeptide of claim 1…” instead.
Claim 3 recites “wherein the binding domains is joined …”. It should read as “wherein the binding domain is joined” instead.
Claims 12 and 13 recite “an effective dose of a Wnt signaling agonist according claim 2”. They should read as “an effective dose of the Wnt signaling agonist according claim 2” instead.
Also, claim 3 is objected to under 37 CFR 1.75(c) as being in improper form because a
multiple-dependent claim should refer to other claims in the alternative only and cannot depend from any other
multiple-dependent claim. See MPEP § 608.01(n).
In this case, claim 3 recites “The Wnt signaling agonist of claim 2, wherein the binding domains is joined to the polypeptide of claim 1 through a linker”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 4, and 5-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 4 recites “wherein the Fzd binding domain binds one or more Fzd proteins”. There is insufficient antecedent basis for this limitation in the claim. Claim 2, from which claim 4 depends, recite “a binding domain” and there is no Fzd binding domain recited in this claim. See MPEP 2173.05(e).
Claim 5 recites “wherein the Lrp5/6 binding domain binds one or both of Lrp5 and Lrp6 proteins”. There is insufficient antecedent basis for the limitation “Lrp5/6 binding domain” in the claim. Claim 2, from which claim 5 depends, recite “a binding domain” and there is Lrp5/6 binding domain recited in this claim. See MPEP 2173.05(e). Claims 6-8, which depend from claim 5, are similarly rejected.
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 1-8 and 12-16 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.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description
requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine
whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art
at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions
characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more
evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a
representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant,
identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics
coupled with a known or disclosed correlation between function and structure, or by a combination of such
identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are
adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in
the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to
reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus
which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See,
e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to
that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
Claim 1 is broadly drawn to a Wnt signaling antagonist polypeptide comprising any amino acid sequence set forth in any of SEQ ID N0:1-4, or any variant thereof.
The as filed specification does not provide sufficient written description for the genus of Wnt signaling antagonist polypeptides. There are so many species of different variations and/or modifications within the 4 amino acid sequences SEQ ID NO: 1-4, but the specification fails to provide give any definition of how similar these amino acid sequences are or how close they are. The specification provides only a limited description of four species of genetically engineered antibody mimetic proteins (1AF34, ANK12, 1AF34F7, and 4AF30) which represents the four amino acid sequences of the antagonist proteins of Wnt (instant specification, paragraph 0014). Also, the specification is also limited to one species of human DKK1c as a binding domain of LRP5/6 Fzd proteins (instant specification, paragraphs 0048-0049). However, the specification does not teach other variations within the four amino acid sequences, other binding domains, or other linkers to be used in order to maintain the binding affinity to Fzd proteins. The specification does not provide any description of the structures or sequences of these amino acid modifications within any amino acid sequence of SEQ ID NO: 1-4. Claim 1 recites “Wnt signaling antagonist polypeptide comprising an amino acid sequence set forth in any of SEQ ID No:1-4, or a variant thereof”. This reads on a Wnt antagonist polypeptide comprising any amino acid sequence of the amino acid sequences SEQ ID NO:1-4 or any small fragments of these sequences. However, the specification does not disclose a genus of different amino acid sequences with different lengths and structures of SEQ ID Nos: 1-4 that can be used as a Wnt signaling
antagonist polypeptide. The claims read on a large amount of sequence variations and/or modifications within the 4 sequences themselves which are not disclosed in the specification.
While the claims recite the genus of Wnt signaling antagonist polypeptides of any amino acid sequence in any of the amino acid sequences set forth in SEQ ID NO:1-4, the applicant has not provided any description or reduction to practice of any species within the genus other than the structure of the four species of SEQ ID NO:1-4 and a single species of human DKK1 as a binding domain to be linked to these different sequences and different variations within to form the Wnt signaling agonist polypeptide. The specification does not even disclose how this modification within the 4 amino acid sequences is done. The four amino acid sequences are 192 amino acid long and
modifying any of these sequences gives a very large number of sequence variations and cannot be done randomly and needs to be described to ensure achieving a functioning polypeptide that is linked to a binding domain and still binds to one or more Fzd proteins, and further one or both of Lrp5 and Lrp6 protein effectively. The disclosure
of four species of amino acid sequences is not sufficient to reflect the variation within the genus of Wnt signaling antagonist polypeptide, particularly as the specification does not disclose any known or disclosed correlation between the sequence structures of the different amino acid sequences and effect of this modification on the binding affinity of the Wnt signaling agonist to the Fzd proteins. Further, the art at the time of filing teaches that the effects of modifications (substitutions, deletions) to a protein sequence on its function cannot be determined a priori.
The prior art teaches that these modifications to any of the Wnt signaling polypeptide antagonist amino acid sequences is not predictable since merely inserting one alanine amino acid into the peptide sequence can result in structural changes of the peptide and/or loss of specific functions, folding, or binding. See for example Izumi et al. (Izumi et al., "Design of Peptide-based Inhibitors for Human Immunodeficiency Virus Type 1 Strains Resistant to T-20". The Journal Of Biological Chemistry. 20 February, 2009. (284):8, 4914–4920). In particular, Izumi et al. teaches that utilizing the resistance- associated mutations to design peptides may be useful in effective peptide-based therapies (paragraph 2, column 1, page 4915, lines 15-17). Furthermore, Izumi et al. discloses the different effects of all the different amino acid substitutions in glycoprotein on inhibiting the activity of the protein resistant clones. For instance, Izumi et al. teaches that different amino acid substitutions in T-20 peptide-based inhibitor at the 138 position in glycoprotein gp41 core are not equivalent in their effects on inhibiting different major T-
20-resistant clones compared to the wild type clone (paragraph 2, column 1, page 4916, lines 1-4). Izumi et al. further teaches that only the alanine substitution (T-20 S138A) inhibited replication of T-20-resistant clones as efficiently as the wild-type clone. (paragraph 2, column 1, page 4916, lines 6-11). However, Izumi et al. teaches that
modifying the peptide-based inhibitor by substituting the amino acid at 138 position with valine doesn’t significantly suppress the replication of human immunodeficiency virus (HIV) variants and proline substitution (S138P) drastically decreased the anti-HIV activity of the peptide inhibitor (paragraph 2, column 1, page 4916, lines 13-16). In addition, Izumi et al. discloses that S138W substitution did not show any measurable p24 production or improving replication kinetics (paragraph 1, column 1, page 4918, lines 6-7). Also, Izumi et al. teaches that improving the potency of peptide inhibitors requires intense modeling and iterative testing in in vitro studies that could lead to the design and synthesis of improved peptide drugs and thus cannot be predicted a priori
(paragraph 2, column 1, page 4919, lines 13-20). Although the design of T-20S138A peptide inhibitor is relatively simple as it involves one residue change at one position in the peptide sequence, other T20 peptide inhibitor models require more complicated and specific substitutions and additional testing in order to get the desired improvement and functionality of the peptide. For example, T-2635 peptide inhibitor involves 19 specific substitutions in 38 amino acids and SC34EK peptide inhibitor involves 12 specific substitutions in the original C34 inhibitor (paragraph 2, column 1, page 4919, lines 1- 13). Thus, the state of the prior does not establish that modifying any of the four
disclosed amino acid sequences of the Wnt signaling antagonist polypeptide by at any position was or with any length to result in a Wnt signaling antagonist polypeptide was either well known or well developed at the time of filing.
Therefore, based on the limited description provided in applicant's specification as discussed in detail above for the genus of Wnt signaling antagonist polypeptides and the undeveloped stated of the prior art with respect to the presence of different sequences of linkers and binding domains, the skilled artisan cannot envision the detailed sequence structure of the different amino acid sequences as defined by the specification or the detailed sequence structures of the genus of Wnt signaling antagonist polypeptide encompassed by the claims. As such, the specification does not demonstrate that applicant was in possession of and/or had reduced to practice the generic invention as claimed. Applicant is reminded that adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1602 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Thus, for the reasons outlined above, claims 1-8 and 12-16 do not meet
the requirements for written description under 35 U.S.C. 112, first paragraph.
Double Patenting
Statutory
Claims 9-11 are directed to the same invention as that of claims 9-11, respectively of commonly assigned U.S. patent No. US 12,084,684 B2. Under 35 U.S.C. 101, more than one patent may not be issued on the same invention.
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). The applicant should amend or cancel claims such that the reference and the instant application no longer contain claims directed to the same invention.
Claims 9-11 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 9-11 of prior U.S. Patent No. US 12,084,684 B2. This is a statutory double patenting rejection.
Non- statutory
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, and 7-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-8, and 17-19 of U.S. Patent No. US 12,084,684 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1-3, and 7-8 are anticipated by patent ‘684 claims 1-3, 7-8, and 17-19.
Regarding instant claim 1, issued claim 1 of U.S. Patent No. US 12,084,684 B2 teaches a Wnt signaling antagonist polypeptide comprising an amino acid sequence set forth in any of SEQ ID NO:1-4, which are identical to instant SEQ ID NO:1-4. Therefore, issued claim 1 anticipates claim 1 of the instant application.
Regarding instant claim 2, issued claim 2 of U.S. Patent No. US 12,084,684 B2 teaches a Wnt signaling agonist comprising a Wnt signaling antagonist polypeptide of claim 1, linked to a binding domain having high affinity to one or both of Lrp5 and Lrp6 protein. Therefore, issued claim 2 anticipates claim 2 of the instant application.
Regarding instant claim 3, issued claim 3 of U.S. Patent No. US 12,084,684 B2 teaches that the Lrp5/6 binding domain is joined to the Wnt signaling antagonist polvpeptide through a linker. Therefore, issued claim 3 anticipates claim 3 of the instant application.
Regarding instant claims 7-8, issued claim 7 of U.S. Patent No. US 12,084,684 B2 teaches that the Lrp5/6 binding domain comprises the Lrp5/6 binding domain comprises a bindingportion of a DKK protein C-terminal domain of human DKK2. Therefore, issued claim 7 anticipates claims 7-8 of the instant application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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