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 1-2, 5-6, 9, 31, 38-41, 44, 46-48, 50-56, 63, 68 and 73 are pending and will be examined on the merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Note: hyperlinks at: p 193 and 302
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 73 is 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.
Claim 73 recites a method comprising: (i) assessing a level or activity of GDF15 in a sample from a subject and (ii) administering a GDF15 pharmaceutical composition to the subject if the level of GDF15 is higher than a comparator. Instant claim 73 does not recite what the comparator is or any method steps to arrive at an appropriate comparator. The instant Specification also does not provide an explicit, limiting definition of what the comparator is. This renders the metes and bounds of claim 73 unclear because one of skill in the art would not be able to determine what the subject’s GDF15 levels must be higher than in order to warrant administration of the pharmaceutical composition.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 is dependent on claim 1. Claim 1 recites an antibody comprising three LC CDRs and three HC CDRs. Claim 2, however recites single domain antibodies, which comprise only three HC CDRs. As such, claim 2 does not contain all of the limitations of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Note: for examination, embodiments comprising single domain antibodies will be ignored.
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 6, 9, 38, 40 and 50-53 and 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. This is a written description rejection.
Scope of the claimed antibodies
Instant claim 6
Instant claim 6 is dependent on instant claim 1, with respect to antibody structure, instant claim 6 further limits claim 1 by specifying that the anti-GDF15 antibody of claim 1 comprise one of twelve LC CDR triplet. Each of the twelve LC CDR triplets recites an LCDR1, an LCDR2 and an LCDR3 explicitly by SEQ ID NO. Each of the LC CDRs recited in instant claim 6 is also permitted to have up to 15% sequence variation from the enumerated sequence or comprise up to 20 amino acid substitutions relative to the explicitly enumerated sequence. Instant claim 6 provides no guidance or limitations on which amino acids may be substituted in place of which other amino acids. Instant claim 6 does not recite any of the HC CDRs that any of the LC CDR triplets of instant claim 6 are paired with to form a functional antibody capable of binding GDF15.
Instant claim 9
Instant claims 9 is directed to antibodies capable of performing the recited function of specifically binding to GDF15. Regarding the antibody structure required to perform this function, instant claim 9 contains the limitations that the anti-GDF15 antibody comprise three VH CDRs and three VL CDRs by way of dependency on claim 1. With further respect to antibody structure, instant claim 9 further limits claim 1 by specifying that the anti-GDF15 antibody of claim 1 comprise one of seventeen HC CDR triplets. Each of the seventeen HC CDR triplets recites an HCDR1, HCDR2 and a HCDR3 explicitly by SEQ ID NO. Each of the HC CDRs recited in instant claim 9 is also permitted to have up to 15% sequence variation from the enumerated sequence or comprise up to 20 amino acid substitutions relative to the explicitly enumerated sequence. Instant claim 9 provides no guidance or limitations on which amino acids may be substituted in place of which other amino acids. Instant claim 9 does not recite any of the LC CDRs that any of the HC CDR triplets of instant claim 9 are paired with to form a functional antibody capable of binding GDF15.
Claims 38 and 40
Claims 38 and 40 are directed to distinct pairings of VH and VL sequences (claim 38) and the corresponding HC and LC sequences (claim 40).
Instant claim 38 is directed to antibodies capable of performing the recited function of specifically binding to GDF15. Regarding the antibody structure required to perform this function, instant claim 38 contains the limitations that the anti-GDF15 antibody comprise three VH CDRs and three VL CDRs by way of dependency on claim 1 and the limitation that the antibody comprise a VL comprising the VL CDRs and a VH comprising the VH CDRs via dependency on claim 31. With further respect to antibody structure, instant claim 38 further limits claim 31 by reciting twenty distinct pairings of a VH identified by SEQ ID NO paired with a VL identified by SEQ ID NO. Each VH and VL recited in claim 38 is also permitted to have up to 15% sequence variation from the enumerated sequence or comprise up to 20 amino acid substitutions relative to the explicitly enumerated sequence. Instant claim 38 provides no guidance or limitations on which amino acids may be substituted in place of which other amino acids or restrictions on loci (such as the binding-critical CDR loci) to form a functional antibody capable of binding GDF15. Please note that claim 38 is dependent on claim 31, which is dependent on claim 1. Neither claim 31 nor claim 38 recite specific sequence limitations regarding the binding-critical CDR regions. As such, instant claim 38 permits up to 15% variation of the VL region (16 amino acids) and the VH region (17 amino acids) with all of the substitutions within the binding-critical CDR regions with no limitations on which amino acids may be substituted for which other amino acids.
Instant claim 40 is directed to antibodies capable of performing the recited function of specifically binding to GDF15. Regarding the antibody structure required to perform this function, instant claim 40 contains the limitations that the anti-GDF15 antibody comprise three VH CDRs and three VL CDRs by way of dependency on claim 1 and the limitation that the antibody comprise a VL comprising the VL CDRs and a VH comprising the VH CDRs via dependency on claim 31 and the limitation that the antibody comprise a HC comprising the VH and a LC comprising the VL by way of dependency on claim 39. With further respect to antibody structure, instant claim 40 further limits claim 39 by reciting twenty distinct pairings of a HC identified by SEQ ID NO paired with a LC identified by SEQ ID NO. Each HC and LC recited in claim 40 is also permitted to have up to 15% sequence variation from the enumerated sequence or comprise up to 20 amino acid substitutions relative to the explicitly enumerated sequence. Instant claim 40 provides no guidance or limitations on which amino acids may be substituted in place of which other amino acids or restrictions on loci (such as the binding-critical CDR loci) produce a functional antibody capable of binding GDF15. Please note that claim 40 is dependent on claim 39, which is dependent on claim 31, which is dependent on claim 1. Neither claim 39 nor 31 nor claim 40 recite specific sequence limitations regarding the binding-critical CDR regions. As such, instant claim 40 permits up to 15% variation of the LC region (34 amino acids) and 15% variation in the HC region (67 amino acids) with all of the substitutions within the binding-critical CDR regions with no limitations on which amino acids may be substituted for which other amino acids.
Claims 50-53
Instant claim 50 is directed to nucleic acids encoding antibodies capable of performing the recited function of specifically binding to GDF15. Regarding the antibody structure required to perform this function, instant claim 50 recites that the VH sequence is selected from any of SEQ ID NOs: 9, 13, 17, 21, 30, 39, 48, 55, 59 62, 67, 72, 77, 81, 87, 91, 203 or any sequence with at least 85% identity thereto and permits the VL sequence is select from any of SEQ ID NOs: 100, 108, 116, 124, 128, 136, 140, 207, 211, 216, 220 or any sequence with at least 85% identity thereto. Instant claim 50 provides no guidance or limitations on which nucleic acids encoding which amino acids may be substituted in place of which other nucleic acids encoding which other amino acids or restrictions on loci (such as the binding-critical CDR loci) to form a functional antibody capable of binding GDF15. Please note that claim 50 is an independent claim and recites no specific sequence limitations regarding the binding-critical CDR regions. As such, instant claim 50 permits up to 15% variation of the VL region (50 nucleic acids, corresponding to up to 16 codons) and 15% variation in the VH region (53 nucleic acids, corresponding to up to 17 codons) with all of the substitutions within the binding-critical CDR regions and leaving the potential open for selecting nucleic acids causing serious mutations (e.g., frameshift, truncation, etc.…) that would affect the ability of the antibody to perform the required function of binding GDF15
Description of Claimed Antibodies in specification
The instant Specification discloses twenty antibodies (Deemed “A” through “T”) capable of performing the required function of binding GDF145, each comprising six distinct CDRs, with the HC sequence data for Clones A-T being found on Table 2 of the instant Spec (Specification, Table 2; p 109- 134) and the LC sequence data for Clones A-T being found on Table 1 of the instant Spec (Specification, Table 1; p 69- 88).
The following table summarizes the VH, VL, HC and LC sequence data from across tables 1 and 2 of the instant Specification:
PNG
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200
400
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Greyscale
The instant disclosure does not provide any examples of pairings VH and VLs capable of forming a functional antibody that can bind GDF15 other than the VH and VL pairings depicted in the table above. The instant disclosure does not provide any examples of antibodies comprising variant CDRs, with each variant CDR comprising up to 15% variation with respect to the corresponding explicitly numbered sequence, that are capable of performing the recited function of binding GDF15.
State of the Relevant Art
As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CH1, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. Sela-Culang (Sela-Culang, et al., Front in Immunol. 2013; Vol. 4; Article 302) teaches on the subject of the structural basis of antibody-antigen recognition (Sela-Culang, Abstract). Sela-Culang teaches that there is a lack of intrinsic properties linking epitopic vs non-epitopic residues based on features present in said residues suggests that epitopes depend, to a great extent, on the antibody that recognizes them (Sela-Culang, p 2, ¶ 7). Sela-Culang teaches that antibodies fold in such a manner such that six hypervariable loops of the light and heavy domains of an antibody (three loops on the HC and three on the LC) are folded together and form the antigen binding site (Sela-Culang, p 3, ¶ 2). Sela-Culang teaches that the complimentary determining regions (CDRs) are amino acid sequences within this hypervariable region and that amino acids that define the CDR regions are typically defined based on numbering schemes (e.g., Kabat, Chothia, IMGT) derived from empirical studies of the boundaries between the framework and binding residues of the antibodies (Sela-Culang), p 3, ¶ 3). Sela-Culang teaches that identification of paratopes (the portion of an antibody which binds an antigen) is done through the identification of CDRs but CDRs, as identified by methods such as Kabat, Chothia and IMGT may miss ~20% of antigen binding residues (Sela-Culang, 4, ¶ 1-2). Sela-Culang teaches that each CDR has its own unique amino acid composition (i.e., different from the other CDRs) and each CDR has a unique set of contact preferences (Sela-Culang, p 5, ¶ 1).
Absent the conserved structure provided by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict what an antibody with a particular set of functional properties would look like structurally. As discussed above, neither an epitope nor a paratope can be calculated a priori based on properties of the component amino acids. Furthermore, each and every CDR sequence is unique and distinct and, as such, a CDR sequence cannot be predicted, either from the epitope sequence of from the CDR sequences of the antibody, if known.
In addition to the importance of the CDR regions, Sela-Culang also teaches that framework residues are also play an important role in antigen binding (Sela-Culang, P 7, ¶ 3). These framework residues can be divided into two types. The first are framework residues that actually contact the antigen and therefore are part of the binding site (Sela-Culang, p 7 ¶ 4). The second type of framework residues that affect antigen binding are framework residues that do not directly contact the antigen but affect binding indirectly (Sela-Culang, p 7, ¶ 5). Some of the framework residues are in close proximity to the CDR regions of the parental antibody, with these FR residues providing structural support that permits the CDRs to adopt the right conformation to form the antigen binding.
The other type of framework residues that indirectly affect antigen binding are further from the CDR regions and affect the relative orientation of the VH and VL regions, and thus the orientation of the CDRs relative to each other (Sela-Culang, p 7, ¶ 6). Sela-Culang also teaches that the effect of framework residues on antigen binding is impossible to predict a priori. For example, Sela-Culang teaches that positions in FR-3 of the heavy chain affects the orientation of CDRH1 relative to CDRH2, however this is not always the case, as it has been shown that mutating a Lys in this region for either a Val, Ala or Arg resulted in affinity differences but no structural changes (Sela-Culang, p 7, ¶ 5).
Additionally, at the time of filing, numerous anti-GDF15 antibodies were known in the art. Beaumont, et al., WO 2020039321 A2; Published 2/27/2020; Priority to 8/20/2018 via US 62/765,289) discloses an anti-GDF15 antibody which is a conventional antibody and comprises six distinct CDRs (Beaumont, p 28, lines 7-13).
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that a “representative number of species” means that the species that 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.
As described above, claims 6 and 9 are directed to unpaired HC or LC triplets. A disclosure of 20 antibodies is not sufficient to be representative of the genus of the (yet undetermined) antibody CDR sequences, when paired with an enumerated CDR triplet of claims 6 or 9 forms a function antibody capable of binding GDF15. As described above, claims 50-53 are directed to pairings of 17 choices of VH nucleotide sequences independently paired with any one of 11 VL nucleotide sequences. This amounts a total of 187 claimed combinations of VH and VL nucleotide sequences. A disclosure of 20 combinations of VH and VL sequences capable of forming a functional antibody capable of binding GDF15 is not sufficient to be representative of the claimed 187 combinations.
Additionally, all of claims 6, 9, 38, 40 and 50 (all of the claims that recite antibody SEQ ID NOs) are directed to variants that comprise up to 15% variation from their respective parental SEQ ID NO sequence and all of these claims permit all of this 15% variation to be within the binding-critical CDR regions. The fact that no limitations are imposed regarding which amino acids may be substituted for which other amino acids leads to all of these being impossibly large genera.
To demonstrate how large the genera permitting up to 15% variation in the CDR regions are, claim 38 will be used as an example. Claim 38 permits up to 17 amino acid changes in the VH sequences and all are permitted to be in the VH CDR regions, which comprise around 40 amino acids. Using the combination (nCr) formula from statistics, there are 8.9 *1010 ways to select 17 amino acids from amongst 40. After that, one must multiply by 1917 because after selecting the amino acids to be substituted, one must select from the remaining 19 amino acids for each of the 17 substitutions. The final number is 4.9 * 1032 different ways to select 17 amino acids from the CDR regions and then replace them with one of the remaining amino acids. A disclosure of 20 antibodies is nowhere near sufficient to be representative of such unfathomably large genera, as the 20 disclosed antibodies represent 4.1 *10-30 % of the encompassed species.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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.
As noted above, the art generally accepted that the combination of the CDRs within the VH and VL pair of an antibody was the minimum structure essential for binding specificity and the framework residues also play a role in antigen binding and a disclosure of an antigen or epitope does not permit a skilled artisan to envision the structure an antibody would need to have to bind that antigen or epitope, even if the amino acid sequence of that epitope is known.
The teachings of Sela-Culang make very clear that a structure-function relationship between an antibody’s CDRs and the epitope it binds is not understood well enough to permit a skilled artisan to analyze an epitopic sequence and envision, a priori, the required CDR structure required to form a functional antibody capable of binding that epitope. Sela-Culang teaches that CDRs are independent structurally and each possess independent binding preferences. There is nothing in the present disclosure nor the prior art that would lead one of skill in the art to believe that the disclosure contains any new discoveries that would supplant these notions. The lack of known structure/function correlation between any given antibody’s VH and VL structure and that antibody’s ability to bind its respective antigen means that it is highly unlikely that a skilled artisan would be able to start with any of the instant claimed partial sequences and arrive, a priori at a functional antibody capable of binding GDF15.
Because the species disclosed are insufficient to be considered representative of either the unfathomably large number of possible variations to the binding-critical CDR regions, coupled with the lack of established structure/function correlation, the claims lack written description and Applicant was not in possession of the invention as claimed.
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) 1-2, 5, 31, 39, 41, 44, 46-48, 54-56, 63 and 68, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beaumont by (Beaumont, et al., WO 2020039321 A2; Published 2/27/2020; Priority to 8/20/2018 via US 62/765,289).
Regarding claims 1, 5, 31, 39 Beaumont discloses an antibody of Embodiment E187, which comprises an anti-GDF15 antibody comprising three HC CDRs and three LC CDRs (Beaumont, p 28, lines 5- 9), wherein the anti-GDF15 antibody comprises VH and VL sequences (CDRs within the respective sequences) (Beaumont, p 29, lines 1-3) and wherein the anti-GDF15 antibody comprises HC and LC sequences (VH is always found in HC and VL is always in LC) (Beaumont, p 29, lines 4-6). Regarding claim 2, Beaumont discloses antibody fragments, including Fc Fusions and scFvs (Beaumont, p 9, lines 20-23). Regarding claim 41, Beaumont discloses anti-GDF15 antibodies binding human GDF15 at an affinity of 600 pM (same as about 599 *10-12M) (Beaumont, p 9, lines 23-27). Regarding claims 56, 63 and 68, Beaumont discloses a method administration (administration inherently results in the antibody contacting a cell, a tissue and a subject) of the anti-GDF15 antibodies of Beaumont as pharmaceutical compositions to subjects in need of reduction of GDF15 levels (Beaumont, p 90, lines 14-19) in methods of treating patients having GDF15-associated cancer (Beaumont, p 91, lines 22-29).
Regarding claim 47, Beaumont discloses a method of making the anti-GDF15 antibody of Beaumont comprising expressing the antibody in mammalian host cells under conditions to produce the antibody (Beaumont, 10). Regarding claim 48, Beaumont discloses isolated nucleic acids encoding the anti-GDF15 antibody of Beaumont (Beaumont, claim 5). Regarding claim 44, Beaumont discloses that 7.5 nM antibody GDF15_001 completely blocked binding of GDF15 to GFRAL ECD (same as reduction of activity of at least 5%....) (Beaumont, p 134, lines 7-12). Regarding claim 46, Beaumont discloses that antibody GDF15_001 was found to bind to human GDF15 but not other TGF beta family members, as determined by Octet assay (Beaumont, p 133, lines 5-24). Regarding claim 47, Beaumont discloses a method of making the anti-GDF15 antibody of Beaumont comprising expressing the antibody in mammalian host cells under conditions to produce the antibody (Beaumont, claims 8-10). Regarding claim 48, Beaumont discloses isolated nucleic acids encoding the anti-GDF15 antibody of Beaumont (Beaumont, claim 5).
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.
Claim 1-2, 5-6, 9, 31, 38-41, 44, 46, 54-56 and 63 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5, 7-11, 16-21, 25, 29-30, 34, 41, 44, 47, and 49 of copending Application No. 18/722,143 (Published as US 2025038259 12/18/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant and copending claims are both directed to anti-GDF15 antibodies comprising the same VH, VL and CDR sequences as the instant application.
Regarding instant claims 1, 5-6, 9, 31, 38, 39 and 40, the copending claims are directed to an anti-GDF15 antibody comprising SEQ ID NOs: 143 (same as instant) and 159 (same as instant) (copending claim 5), comprising a VL of SEQ ID NO: 99 (same as instant) and a VH of SEQ ID NO: 8 (same as instant) (copending claim 4) comprising LCDR1, 2 and 3 of SEQ ID NOs: 92, 93 and 94, respectively (all same as instant) and HCDR1, 2 and 3 of SEQ ID NOs: 1, 2 and 3, respectively (all same as instant) (copending claim 3). Regarding instant claim 2, copending claim 41 is directed intact IgA, IgG, etc... antibodies. Regarding claims 54-55, copending claims 29 and 30 are directed to pharmaceutical compositions comprising anti-GDF15 antibodies. Regarding claim 41, as evidenced by the instant Specification, an antibody having the CDRs as the copending claimed antibody has a Kd of 41.7*10-12 M (Specification, ¶ 0051) Regarding claim 44, as evidenced by the instant Specification, an antibody having the CDRs as the copending claimed antibody would inherently have little to no binding to other TGF beta family members (Specification, ¶ 0473).
Regarding claim 46, as evidenced by the instant Specification, an antibody having the CDRs as the copending claimed antibody would inherently have little to no binding to other TGF beta family members (Specification, ¶ 0473). Regarding claims 44, 56 and 63, copending claims are directed to a method of inhibiting GDF15 comprising administering the anti-GDF15 antibody of the ‘143 application to a subject (copending claims 1-3) and, as evidenced by the instant Specification, an antibody having the CDRs of the copending claimed antibody would inherently inhibit GDF15 by about 5% (Specification ¶ 0026). Regarding claim 56 and 63 specifically, administering the anti-GDF15 antibody of the method of claims 1-3 of the ‘143 application inherently results with the anti-GDF15 contacting a cell, a tissue and a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1-2, 5-6, 9, 31, 38-41, 44, 46-48, 50-56, 63 and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5, 7-11, 16-21, 25, 29-30, 34, 41, 44, 47, and 49 of copending Application No. 18/722,143 (Published as US 2025038259 12/18/2025) as applied to claims 1-2, 5-6, 9, 31, 38-41, 44, 46, 54-56 and 63 above and in further view of Beaumont by (Beaumont, et al., WO 2020039321 A2; Published 2/27/2020; Priority to 8/20/2018 via US 62/765,289).
The teachings of the ‘143 application are discussed above.
The ‘143 application does not teach that the anti-GDF15 antibody of the ‘143 application is produced in a method comprising culturing a host cell comprising a vector comprising a nucleic acid encoding the anti-GDF15 antibody of the ‘143 application. The ‘143 application does not teach that the anti-GDF15 antibody of the ‘143 application is administered to a subject having cancer.
Beaumont teaches an antibody of Embodiment E187, which comprises an anti-GDF15 antibody comprising three HC CDRs and three LC CDRs (Beaumont, p 28, lines 5- 9), wherein the anti-GDF15 antibody comprises VH and VL sequences (CDRs within the respective sequences) (Beaumont, p 29, lines 1-3) and wherein the anti-GDF15 antibody comprises HC and LC sequences (VH is always found in HC and VL is always in LC) (Beaumont, p 29, lines 4-6). Beaumont teaches a method administration of the anti-GDF15 antibodies of Beaumont as pharmaceutical compositions to subjects in need of reduction of GDF15 levels (Beaumont, p 90, lines 14-19) in methods of treating patients having GDF15-associated cancer (Beaumont, p 91, lines 22-29). Beaumont teaches a method of making the anti-GDF15 antibody of Beaumont comprising expressing the antibody in mammalian host cells under conditions to produce the antibody (Beaumont, 10), wherein the host cell comprises a vector (Beaumont, claims 7-8), wherein the vector comprises an isolated nucleic acid encoding the anti-GDF15 antibody of Beaumont. Beaumont also teaches that the host cell is a mammalian cell that is a CHO cell (Beaumont, claim 9).
It would be prima facie obvious to apply the anti-GDF15 antibody production method of Beaumont, said method comprising expressing the antibody in mammalian CHO host cells under conditions to produce the antibody, wherein the CHO host cell comprises a vector and wherein the vector comprises an isolated nucleic acid encoding the anti-GDF15 antibody of Beaumont to produce the anti-GDF15 antibody of the ‘143 Application. The net result of this application would be a method of producing the anti-GDF15 antibody of the ‘143 application comprising culturing a CHO host cell comprising a vector comprising an isolated nucleic acid encoding the anti-GDF15 antibody of the ‘143 application under conditions wherein the anti-GDF15 antibody of the ‘143 application is expressed. One of ordinary skill in the art would be motivated to do this in order to have a method of making the anti-GDF15 antibody of the ‘143 application. One of skill in the art would have a reasonable expectation of success applying the method of Beaumont to produce the antibody of the ‘143 application because Beaumont teaches that this method is an acceptable method for producing anti-GDF15 antibodies. This additionally reads on claims 50-53 and 47-48.
It would be prima facie obvious to one of ordinary skill in the art to administer the anti-GDF15 antibody of the ‘143 application to a patient having GDF15-associated cancer in view of the teachings of Beaumont. The net result of this application would be a method of treating GDF15-associated cancer comprising administering the anti-GDF15 antibody of the ‘143 application to a patient in such need. One of ordinary skill in the art would be motivated to do this to better treat cancer. One of ordinary skill in the art would have a reasonable expectation of success administering the anti-GDF15 antibody of the ‘143 application to a patient having GDF15-associated cancer in view of the teachings of Beaumont because Beaumont teaches anti-GDF15 antibodies are capable of treating anti-GDF15-associated cancer. This additionally reads on claim 68.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Subject Matter Free of Prior Art
The following is a statement of reasons for the indication of allowable subject matter:
Antibodies that bind GDF15 and comprise the specific VH and VL sequence pairings recited in claim 38 are free of prior art. A multi-database sequence search was performed for each of the claimed VH and VL sequence. The table below depicts the next nearest prior art for each of the VH and VL sequences of claim 38:
PNG
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200
400
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Greyscale
Note that none of the prior art matches correspond to the VH or VL of an antibody capable of performing the required function of binding GDF15. As such, it would be unlikely that one of skill in the art would be motivated to start with any of the next nearest prior art match sequences, perform the required manipulation to arrive at an instant claimed sequence and then pair the resultant VH/VL sequence with a corresponding complementary sequence and arrive at a functional antibody capable of binding GDF15. As such, that bind GDF15 and comprise the specific VH and VL sequence pairings recited in claim 38 are free of prior art.
Conclusion
Claims 1-2, 5-6, 9, 31, 38-41, 44, 46-48, 50-56, 63, 68 and 73 are rejected.
The Specification is objected to.
No claims are allowed.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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