Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Response to Election/Restriction filed on July 29, 2026 is acknowledged. Claims 1-21, 23 are pending in the instant application.
Election/Restrictions
Applicant elected Group I (claims 1-19 and 21) and SEQ ID NO:105 from List I with traverse in the response filed July 29, 2026.
Applicant argues that “In this case, the Patent Office alleges a posteriori lack of unity of invention on the basis of the teachings of WO2021107603 in view of CN113286812. However, Applicant submits that this finding of lack of unity of invention is premature in the present application as a full search of the prior art has yet to have been conducted. Applicants argues that the set of reference do not disclose the same special technical feature. Applicant’s argue that WO2021107603 discloses Fc-GDF15 and it is a monoFc and has substitutions at different positions compared to the instant claims. CN113286812 discloses heterodimers and thus this is different from the homodimer Fc variant described in the instant application. Applicant’s arguments have been fully considered but not found persuasive. Applicants are arguing limitations that are NOT found in instant claim 1 and is not a requirement of the specifical technical feature. The shared technical feature between groups 1-3 is a fusion polypeptide comprising GDF15 and Fc. However, W2021107603 (reference cited in IDS) in view of CN113286812 (cited in Applicant’s IDS) teaches the fusion peptide (GDF15 and FC) meeting the limitations of the shared technical feature of inventions 1-3 (see claims 1-25 of WO2021107603 and paragraph 0427 of CN113286812). CN113286812 teaches the mutations of the Fc for the purpose of half-life extension. One of ordinary skill in the art would have been motivated to make these substitutions in the fusion peptide of WO2021107603 to further increase the half-life which is beneficial therapeutically.
Therefore, inventions 1-3 lack unity of invention in view of WO2021107603 and CN113286812.
The restriction is deemed proper and is made FINAL in this office action. Claims 5, 10, 16, 20 and 23 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 5 and 10 are withdrawn as the elected species is SEQ ID NO:105 which is SEQ ID NO:46 with a three n-terminal deletion and a substitution at position 439 and not 356. *Please note that the elected Species is found free of the art and thus the search was extended to other species an art was found.
Claims 1-4, 6-9, 11-15, 17-19, 21 are examined on the merits of this office action.
Claim Objections
Claims 17-18 are objected to for the following reason: Claims 17-18 recites amino acid sequences with 4 or more defined amino acids. The peptide sequences are missing the sequence identifier. The proper way to claim a peptide sequence is for example, (G4S)n (SEQ ID NO: X) (see 37 CFR 1.821(d)). This error should be corrected.
Claim 18 claims “the hybrid peptide linker”. This limitation should be amended to recite -rigid/flexible hybrid linker-.
Claim 19 claims “the fusion protein”. This limitation should be amended to recite -the GDF15 fusion protein-.
Claim Rejections - 35 USC § 112, First Paragraph
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 1-4, 6-9, 11-15, 17-19, 21 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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.
Scope of the claims
The claims encompass broad genera of GDF15 FC fusion proteins. Claim 12 encompasses A GDF 15 active domain comprising SEQ ID Nos: 46- 66 or sequences having at least 85%, 90%, 95% or 99% sequence identity thereto. Because claim 12 depends from claim 1 the variant must retain the biological activity of GDF 15. Claim 14 similarly encompasses complete fusion proteins having at least 85% ninety percent 95% or 99% identity to the recycled fusion protein sequences. Claim 15 encompasses complete fusion proteins having at least 95% identity. The percentage identity limitations encompass substantially more sequences than this expressly disclosed species. In particular the claims do not limit substitutions to the specific positions or amino acid changes exemplified in the specification. For the whole fusion claims the percentage identities determined over the complete FC linker GDF 15 protein and does not specify where the permitted sequence differences must occur. Thus substantial variation may potentially be concentrated within the GDF15 active domain, FC region or both. Furthermore the FC portion of the claim genus is also broad. The specification states “As used herein, “IgG” or “IgG antibody” refers to an antibody having the structure of a naturally occurring immunoglobulin G molecule. IgG antibodies include, for example, IgG1, IgG2, IgG3, and IgG4, IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc represent the Fc or Fc region of IgG1, IgG2, IgG3, and IgG4, respectively. The IgG Fc in the fusion protein herein can be IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc, preferably IgG1 Fc, IgG4 Fc” (see paragraph 0011).
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification provides actual examples of particular fusion proteins containing specifically selected FC variants linkers and GDF 15 domains. The GDF15 examples include wild type mature GDF 15 and selected end terminal truncations and substitutions. Likewise the FC examples employ selected substitutions including modifications at positions 356 and or 439 and other specifically identified FC modifications. These examples evidence possession of the particular proteins tested and closely defined species but do not demonstrate actual reduction to practice across the considerably broader sequence identity genera. The disclosure does not appear to test representative variance containing the breadth of the sequence changes permitted by the 85% identity limitations.
Accordingly, the disclosed examples do not constitute representative species of the claimed genus. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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 thereof.
The specification identifies particular GDF 15 substitutions and positions at which substitutions may be made. However the greater than equal to 85% identity genus is not limited to those positions or substitutions. It encompasses numerous additional combinations of amino acid changes not specifically identified as retaining GDF 15 activity. Similarly the FC disclosure identifies particular engineered substitution whereas the whole fusion sequence identity claims permit additional variation through the Fc-GDF15 molecule. Although the specification provides identifying characteristics for the specifically disclosed species it does not sufficiently identify structural characteristics common to the full claim genus that would permit a skilled artisan to recognize which of the additional sequence variants are members of the claimed functional genus.
Regarding IgFc variant, Although the specification exemplifies numerous particular FC sequences containing selected substitutions including substitutions at positions 356 and 439 the broader disclosure encompasses multiple IgG Fc rate the 112B with respect to the FC variant because it's unclear what these positions are referring to in terms of which sequence of IG GFC subclasses and substantial additional sequence variation. The specification must therefore provide representative species or other identifying characteristics sufficient to demonstrate possession of FC variants across the claim breath rather than merely the particular FC backbones in mutations exemplified.
Physical/Chemical Properties
The specification describes structural properties of the disclosed proteins including the GDF 15 sequence FC region peptide linker and particular amino acid substitutions and truncations. However these properties primarily characterize the exemplified proteins. The disclosure does not establish that proteins throughout the full greater than equal to 85% identity genus share physical or chemical properties sufficient to distinguish variants that retain the required GDF 15 activity from variants that do not. The same concern applies to broader FC variation where FC function is required.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The claims require more than sequence similarity. The GDF 15 domain must retain GDF 15 biological activity. Where homodimerization is required by the particular claim the FC must also retain the ability to form homodimers. Functional language can contribute to written description when the art or specification establishes a sufficiently known correlation between structure and function. Here however the specification principally demonstrates activity for selected GDF 15 variants in fusion proteins. It does not appear to establish a structure function correlation sufficient to predict that the substantially broader range of the sequences encompassed by greater than equal to 85% identity will retain the desired activity. Regarding claim 14, the identities measured over the entire fusion protein thus permitting sequence differences that are not evenly distributed. A pure team may satisfy the overall identity threshold while having substantially greater divergent with the smaller functionally important GDF 15 domain. This specification does not identify a corresponding structural rule establishing which such variants will retain GDF 15 biological activity.
Method of Making
The specification provides methods sufficient to make the disclosed fusion proteins using conventional recombinant techniques. However the ability to physically make sequences falling within a percentage identity genus is not by itself evidence that the inventors possess the claim functional genus. The issue is not an inability to synthesize variant proteins but the absence of disclosed identifying which of the numerous possible variants permitted by the claims will possess the claims biological activity.
Conclusion
The specification demonstrates possession of numerous specific FCGDF 15 fusion proteins and specifically identified variants but does not reasonably convey possession of the full breadth of the claim sequence identity genus. In particular it does not provide a representative number of species across the greater than equal to 85% identity scope or sufficient common structural characteristics correlated with retention of GDF 15 biological activity by which a skilled artisan could recognize members of the full genus.
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.
Claims 1-4, 6-9, 11-15, 17-19 and 21 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 3 Define the FC variant by amino acid substitution at positions 356 and or 439 according to EU numbering but neither claimed 3 nor claim one identifies the particular iggfc sequence to which these positions refer. The specification states that ““As used herein, “IgG” or “IgG antibody” refers to an antibody having the structure of a naturally occurring immunoglobulin G molecule. IgG antibodies include, for example, IgG1, IgG2, IgG3, and IgG4, IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc represent the Fc or Fc region of IgG1, IgG2, IgG3, and IgG4, respectively. The IgG Fc in the fusion protein herein can be IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc, preferably IgG1 Fc, IgG4 Fc” (see paragraph 0011). Accordingly it is unclear which IGGFC sequence provides the reference sequence for determining the recited amino acid positions and substitutions. Therefore a person of ordinary skill in the art would not be informed with reasonable certainty of the scope of the claimed FC variant encompassed by the claims. Claims 2-19, 21 Are also rejected due to their ultimate dependence on claim one and not further clarifying this point of confusion. Regarding claim 7, Although the recited SEQ ID Nos. Provide particular reference sequences the percentage identity alternatives permit amino acid differences throughout those sequences without specifying which residues must be retained or how the substitution is defining the claim FC variant are to be identified in such sequence variants. In particular it is unclear whether residues corresponding to the FC positions identified elsewhere in the claims must be maintained made themselves be substituted to have such positions are to be determined in sequences containing substitutions insertions or deletions. Accordingly the meets and bounds of the FC variant encompassed by the percentage identity alternatives cannot be determined with reasonable certainty.
Claim 3 claims “preferably, the Fc variant” and “more preferably…” These phrases render the scope of the claim unclear. These terms express preferences rather than clearly defining whether the subsequently recited FC substitutions are required limitations of the claim. Thus it is unclear whether the preferred and more preferred substitutions limit the scope of claim 3 or identify optional embodiments.
Claim 4 claims “preferably, the Fc variant”. This phrase renders the scope of the claim unclear. The term “preferably” expresses preferences rather than clearly defining whether the subsequently recited FC substitutions are required limitations of the claim. Thus it is unclear whether the preferred substitutions limit the scope of claim 4 or identify optional embodiments.
Claim 6 claims “The fusion protein of claim 1,wherein the Fc variant further comprises the following mutations: amino acid substitutions at position 234 and position 235 of the IgG Fc with alanine (AA), and/or amino acid deletion at position 447 of the IgG Fc according to EU numbering. The limitation in bold renders the claim indefinite. It is unclear whether the substitution at position 234 and 235 is a single Alanine or two alanine given that the parenthesis is suggesting that there are two alanine. Given the multiple possible interpretation of the claim, it is unclear what the metes and bounds of the claim is. If Applicant is wanting only a single Ala substitution, the parenthesis “(AA)” should be removed from the claim.
Claim 7 claims “wherein the Fc variant comprises an amino acid sequence of one of the following group, or an amino acid sequence having at least 85%, 90%, 95%or 99% sequence identity to one of the following group: SEQ ID NO: 1-22, SEQ ID NO: 27, SEQ ID NO: 29-45.” The first limitation of “one of the following group” is indefinite because Applicants do not list out the groups for that limitation. Applicants only list at the groups for the second “one of the following group…” Thus, one cannot determine the metes and bounds of the claims.
Claim 8 recites the limitation “…of one of the following group, or an amino acid sequence having at least….to one of the following group: SEQ ID NO…” The first limitation of “one of the following group” is indefinite because Applicants do not list out the groups for that limitation. Applicants only list at the groups for the second “one of the following group…” Thus, one cannot determine the metes and bounds of the claims. Furthermore, claim 8 claims “wherein the GDF15 active domain comprises an amino acid sequence selected from one of the following group, or having at least 85%, 90%, 95% or 99% sequence identity to one of the following group:SEQ ID NO: 46; 1-14 amino acid truncations at the N-terminal of SEQ ID NO:46, and/or 1-3 amino acid substitutions in SEQ ID NO:46. The claim is indefinite because the bolded limitation is conflicting with the rest of the claim. It is not possible to have a sequence comprising SEQ ID NO:46 at the same time as having 1-14 truncations and 1-3 substitutions of SEQ ID NO:46.
Claim 9 claims “…wherein the GDF15 active domain comprises an amino acid sequence selected from one of the following group: SEQ ID NO: 46; 1-14 amino acid truncations at the N-terminal of SEQ ID NO:46, and/or 1-3 amino acid substitutions in SEQ ID NO:46. The claim is indefinite because the bolded limitation is conflicting with the rest of the claim. It is not possible to have a sequence comprising SEQ ID NO:46 at the same time as having 1-14 truncations and 1-3 substitutions of SEQ ID NO:46.
Claim 11 recites the limitation "wherein the N-terminal of SEQ ID NO:46" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 claims “preferably..”. This phrase renders the scope of the claim unclear. The term “preferably” expresses preferences rather than clearly defining whether the subsequently recited sequence are required limitations of the claim. Thus it is unclear whether the preferred sequences limit the scope of claim 13 or identify optional embodiments.
Claim 15 claims “preferably..”. This phrase renders the scope of the claim unclear. The term “preferably” expresses preferences rather than clearly defining whether the subsequently recited fusion protein sequence are required limitations of the claim. Thus it is unclear whether the preferred sequences limit the scope of claim 15 or identify optional embodiments.
Claim 18 claims “preferably..”. This phrase renders the scope of the claim unclear. The term “preferably” expresses preferences rather than clearly defining whether the subsequently recited linker sequence are required limitations of the claim. Thus it is unclear whether the preferred sequences limit the scope of claim 18 or identify optional embodiments.
Claim 21 claims “preferably..”. This phrase renders the scope of the claim unclear. The term “preferably” expresses preferences rather than clearly defining whether the subsequently recited “pharmaceutical composition” is required limitations of the claim. Thus it is unclear whether the preferred sequences limit the scope of claim 21 or identify optional embodiments.
Claims 12-15 recited the limitation “…of one of the following group, or an amino acid sequence having at least….to one of the following group: SEQ ID NO…” The first limitation of “one of the following group” is indefinite because Applicants do not list out the groups for that limitation. Applicants only list at the groups for the second “one of the following group…” Thus, one cannot determine the metes and bounds of the claims.
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.
Claim(s) 1, 3, 6-9, 11-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xiong (WO2019199685 A1).
Xiong teaches a fusion protein comprising a GDF15 peptide joined to an FC region via a linker (see claim 1). Xiong teaches wherein the GDF15 portion is the active domain of GDF15 in which the first three amino acids are removed (see page 6, lines 37-39, see also SEQ ID NO:41 for example) which meets the limitations of a fusion comprising instant SEQ ID NO:46 with first three amino acids removed and instant claims 8-9 and 11-13. Xiong further teaches wherein the IgG Fc variant has an amino acid substitution at position 356 (see for example Table 3 SEQ ID NO:27, 32). Regarding claim 1, Xiong teaches a linker comprising (G4S)n (see claim 7). Regarding claims 1, 8-9, 11, Xiong teaches a fusion protein wherein the Fc variant is fused to the N-terminus of the truncated GDF15 molecule (see SEQ ID NO:41 and SEQ ID NO:39). Regarding claim 3, Xiong teaches wherein the E356 is substituted to lysine (see SEQ ID NO:27). Regarding claim 6, Xiong teaches substitution at positions 234 and 235 with alanine residues (see SEQ ID Nos:56-57, 37 for example). Regarding claim 7, Xiong teaches wherein the Fc variant has at least 85% sequence identity to SEQ ID NO:1 (see SEQ NO:32). Regarding claim 14, Xiong teaches a fusion protein sequence having at least 85% sequence identity to SEQ ID NO:105 (see SEQ ID NO:40).
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1-3, 7-9, 11-15, 17-19, 21 are rejected under 35 U.S.C. 103 as being unpatentable over Gonciarz (WO2019195091 A1, cited Applicant’s IDS) in view of Xiong (US20160168213).
Gonciarz teaches a fusion protein comprising GDF15 and Fc variant (see paragraph 0008) wherein the IgG4 Fc unit is linked via a linker to the N-terminus of GDF15 (see paragraph 0008, SEQ ID NO:2, see also Example 1). Regarding claims 2 and 19, Gonciarz further teaches wherein the fusion proteins self-associate to form homodimers (see paragraph 0073). Regarding claims 1, 8-9, 11-13, Gonciarz teaches wherein the GDF15 comprises SEQ ID NO:46 with a three amino acid truncation (see SEQ ID NO:2). Regarding claims 17-18, Gonciarz teaches the peptide linker comprises (G4S)n(AP)m(G4S)n (see SEQ ID NO:2). Regarding claim 21, Gonciarz teaches pharmaceutical formulations comprising said homodimeric fusion proteins (see abstract, paragraph 0011).
Gonciarz is silent to either a substitution at 356 or 439 of the IgG Fc. However, Xiong teaches of fusion proteins comprising GDF15 and an FC domain (see claims 1-2). Xiong teaches wherein the fusion protein can form homodimers or heterodimers (see paragraph 0036). Xiong teaches wherein the fusion protein comprises an Fc variant with a E356D substitution (a conservative substitution, see paragraph 0242, SEQ ID Nos:20, 17, 16, 281) with a linker fused to the GDF15 protein (see claims 1-7, SEQ ID NO:55 is the 3 n terminal truncated GDF15).
It would have been obvious before the effective filing date of the claim invention to one of ordinary skill in the art to modify the GDF15 FC fusion protein taught by Gonciarz to incorporate the E356D substitution in the FC domain as taught by Xiong. One of ordinary skill in the art would have been motivated to make such a modification because Xiong teaches the use of an FC variant comprising the E356D substitution in a GDF15-FC fusion protein thereby providing an express teaching that such an FC variant is suitable for use in the same type of GDF15 FC fusion protein taught by Gonciarz. One of ordinary skill in the art would have had a reasonable expectation of success in making this modification because both Gonciarz and Xiong teach GDF15 proteins fused through a linker to an FC domain and forming dimeric fusion proteins and Xiong specifically demonstrates the compatibility of the E356D Fc variant with a GDF 15 FC fusion construct. Thus, incorporating Xiong’s known E356D FC substitution into the GDF15 FC fusion protein of Gonciarz would have amounted to the application of a known FC modification to a similar GDF15-FC fusion protein according to known methods, with the expectation that the resulting fusion protein would retain the respective functions of the GDF15-Fc protein and yield predictable results (see MPEP 2143).
Regarding claim 3, the combined references teach a Asp at position 356.
Regarding claim 7, Xiong teaches a Fc peptide variant comprising at least 85% sequence identity to SEQ ID NO:1 (see SEQ ID Nos:20, 281).
Regarding claims 14-15, the combined references of Gonciarz and Xiong teach many fusion proteins comprising at least 85% and 95% sequence identity to instant SEQ ID NO:67 amongst other claimed SEQ ID NOs. Xiong teaches SEQ ID NO:20 and 77 which is 95% sequence identity to instant SEQ ID NO:67 and 93% to SEQ ID NO:105.
Double Patenting
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 1-4, 6-9, 11-15, 17-19, 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21, 23-36, 38-39 of copending Application No.18/682002 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A GDF15 fusion protein comprising an immunoglobulin Fc variant, a peptide linker and a GDFl5 active domain, wherein the Fe variant comprises amino acid substitutions at position 356 and/or position 439 of the IgG Fc according to EU numbering ;the GDF15 active domain is a full-length mature GDF15 protein, a N-terminal truncated GDF15 protein, or any variant that retains the biological activity of GDF15; the peptide linker is selected from rigid peptide linker or rigid/flexible hybrid peptide linker; and the C-terminal of the Fc variant is linked via a peptide linker to the N-terminal of the GDF15 active domain” (claim 1); wherein the Fc variant has the ability to form homodimers (claim 2); herein the Fc variant comprises one of the following mutations: K439D, K439E, K439Q, K439A, K439N;preferably, the Fc variant comprises one of the following mutations: K439D, K439E, K439Q (claim 4); E356R, E356Q, E356A, E356N;preferably, the Fc variant comprises the E356R mutation (Claim 5); Fc variant further comprises the following mutations: amino acid substitutions at position 234 and position 235 of the IgG Fe with alanine (AA), and/or amino acid deletion at position 447 of the IgG Fe according to EU numbering (claim 6); an amino acid sequence of one of the following group, or an amino acid sequence having at least 85%, 90%, 95%or 99% sequence identity to one of the following group: SEQ ID NO: 1-22, SEQ ID NO: 27, SEQ ID NO: 29-45 (claim 7); GDF15 active domain comprises an amino acid sequence selected from one of the following group, or having at least 85%, 90%, 95% or 99% sequence identity to one of the following group:SEQ ID NO: 46 (claim 8); wherein the N-terminal of SEQ ID NO: 46 is truncated by 3, 4 or 14 amino acids (claim 11); fusion protein comprises an amino acid sequence of one of the following group, or an amino acid sequence having at least 85%, 90%, 95% or 99% sequence identity to one of the following group: SEQ ID NO: 67-78, SEQ ID NO: 80-102, SEQ ID NO: 105-118 (claim 14); A homodimeric fusion protein comprising the fusion protein (claim 19); linkers comprising G4S and AP (claim 18); a pharmaceutical formulation thereof (claim 21).
Co-pending Application claims “A method of treating obesity-related diseases comprising administering to a subject a therapeutically effective amount of Fc-GDF15 fusion protein; wherein the fusion protein comprises a GDF15 active domain and an Fe variant; the C-terminal of the Fe variant is linked directly or via a peptide linker to the N-terminal of the GDF15 active domain; the Fe variant comprises amino acid substitutions at position 356 and/or position 439 of the IgG Fe according to EU numbering” (claim 21). Co-pending Application further claims wherein the variant can form homodimers (see claim 23); K439 D substitution (claim 25); E356R (claim 26); 234/235 AA substitution (claim 27); SEQ ID Nos:1-22, 27 and 29-45 which are identical to the instant corresponding SEQ ID Nos (claim 28); N-terminal truncated GDF15 (claim 29); SEQ ID NO:46 (claims 30-31); fusion protein comprising SEQ ID NO:105 (same as instant SEQ ID NO:105 with claimed linkers, see claim 36).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-4, 6-9, 11-15, 17-19, 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-19, 21 of copending Application No.18/294397 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A GDF15 fusion protein comprising an immunoglobulin Fc variant, a peptide linker and a GDFl5 active domain, wherein the Fe variant comprises amino acid substitutions at position 356 and/or position 439 of the IgG Fc according to EU numbering ;the GDF15 active domain is a full-length mature GDF15 protein, a N-terminal truncated GDF15 protein, or any variant that retains the biological activity of GDF15; the peptide linker is selected from rigid peptide linker or rigid/flexible hybrid peptide linker; and the C-terminal of the Fc variant is linked via a peptide linker to the N-terminal of the GDF15 active domain” (claim 1); wherein the Fc variant has the ability to form homodimers (claim 2); herein the Fc variant comprises one of the following mutations: K439D, K439E, K439Q, K439A, K439N;preferably, the Fc variant comprises one of the following mutations: K439D, K439E, K439Q (claim 4); E356R, E356Q, E356A, E356N;preferably, the Fc variant comprises the E356R mutation (Claim 5); Fc variant further comprises the following mutations: amino acid substitutions at position 234 and position 235 of the IgG Fe with alanine (AA), and/or amino acid deletion at position 447 of the IgG Fe according to EU numbering (claim 6); an amino acid sequence of one of the following group, or an amino acid sequence having at least 85%, 90%, 95%or 99% sequence identity to one of the following group: SEQ ID NO: 1-22, SEQ ID NO: 27, SEQ ID NO: 29-45 (claim 7); GDF15 active domain comprises an amino acid sequence selected from one of the following group, or having at least 85%, 90%, 95% or 99% sequence identity to one of the following group:SEQ ID NO: 46 (claim 8); wherein the N-terminal of SEQ ID NO: 46 is truncated by 3, 4 or 14 amino acids (claim 11); fusion protein comprises an amino acid sequence of one of the following group, or an amino acid sequence having at least 85%, 90%, 95% or 99% sequence identity to one of the following group: SEQ ID NO: 67-78, SEQ ID NO: 80-102, SEQ ID NO: 105-118 (claim 14); A homodimeric fusion protein comprising the fusion protein (claim 19); linkers comprising G4S and AP (claim 18); a pharmaceutical formulation thereof (claim 21).
Co-pending Application claims a fusion protein comprising GD15 active domain and an Fc Variant linked via the c-terminal the Fc, wherein the Fc variants has a 356 or 439 substitution (claim 1). Co-pending Application further claims wherein the variant can form homodimers (see claim 2); K439 D substitution (claim 4); E356R (claim 5); 234/235 AA substitution (claim 6); SEQ ID Nos:1-22, 27 and 29-45 which are identical to the instant corresponding SEQ ID Nos (claim 7); N-terminal truncated GDF15 (claim 9); SEQ ID NO:46 (claims 9-10); fusion protein comprising SEQ ID NO:105 with the instant linkers (same as instant SEQ ID NO:105, see claim 15); homodimeric fusion protein (claim 17).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/ Primary Examiner, Art Unit 1654
