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 Status
The amendments and remarks filed 07/13/2026 are acknowledged.
Claims 1-5, 11-16, 18, 20, 26, 32, 34-36, 41-46, 120-122, 125, 127, and 135-136 are pending.
Claims 6-10, 17, 19, 21-25, 27-31, 33, 37-40, 47-119, 123-124, 126, 128-134, and 137-141 are canceled.
Applicant’s election without traverse of Group I, claims 1-5, 11-16, 18, 20, 26, 32, 34-36, 41-46, 125, and 127, in the reply filed on 07/13/2026 is acknowledged. Applicant’s election without traverse of the following species in the reply filed on 07/13/2026 is acknowledged: SEQ ID NOs: 1, 3, 5, and 7 for the sequences of the FRH 1-4, respectively, SEQ ID NOs: 2, 4, and 6 for the sequences of the CDRs H1-3, respectively, SEQ ID NO: 57 for the VH, SEQ ID NOs: 33, 35, 37, and 39 for the sequences of the FRL 1-4, respectively, SEQ ID NOs: 34, 36, and 38 for the sequences of the CDRs L1-3, respectively, and SEQ ID NO: 62 for the VL.
The Examiner notes that it appears Applicant mislabeled the above elected sequences and instead meant to elect SEQ ID NOs: 1, 3, 5, and 7 for the sequences of the FRL 1-4, respectively, SEQ ID NOs: 2, 4, and 6 for the sequences of the CDRs L1-3, respectively, SEQ ID NO: 57 for the VL, SEQ ID NOs: 33, 35, 37, and 39 for the sequences of the FRH 1-4, respectively, SEQ ID NOs: 34, 36, and 38 for the sequences of the CDRs H1-3, respectively, and SEQ ID NO: 62 for the VH, which are set forth in the instant claims. The Examiner will proceed with this interpretation of the election for examination.
Claims 4-5, 120-122, and 135-136 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/13/2026.
Therefore, claims 1-3, 11-16, 18, 20, 26, 32, 34-36, 41-46, 125, and 127 are under examination.
Priority
The instant application claims priority to European application EP22204963.7. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Priority is given with the earliest effective filing date of 11/01/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/30/2024, 06/14/2024, and 05/05/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Further, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because:
(1) Figures 3A-B and 7A-B are in color. A petition to accept color drawings is required to have color in the drawings.
(2) Figure 6 comprises multiple panels. 37 CFR 1.84(u) states that the different views must be numbered in consecutive Arabic numerals and that "partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter". Each panel should be separately numbered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 includes the limitation “preferably.” MPEP 2173.05(d) states, “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim.” The “preferably” should be removed entirely. Appropriate correction is required.
Claim 46 is objected to because of the following informalities: Claim 46 does not end in a period. MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.” Appropriate correction is required.
Improper Markush Grouping
Claims 1 and 2 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a "single structural similarity" and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a "single structural similarity" and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping within each of the CDRH 1-3, as set forth in instant claim 1, and within each of the CDRL 1-3, as set forth in instant claim 2, is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the alternatives do not share both a substantial structural feature and a common use that flows from the substantial structural feature. For example, SEQ ID NO: 34 and SEQ ID NO: 52 as set forth as options for the CDRH1 in claim 1 have 0% sequence identity, and SEQ ID NO: 2 and SEQ ID NO: 21 as set forth as options for the CDRL1 in claim 2 only have 27.5% sequence identity. Therefore, the alternatives listed for each of the CDRH 1-3 and the CDRL 1-3 do share both a substantial structural feature and a common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(b)
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 1-3, 11-16, 18, 20, 26, 32, 34-36, 41-46, 125, and 127 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.
Claim 1 recites the limitation “an isolated antibody or antibody fragment which specifically binds to guanylyl cyclase C (GUCY2C), wherein the antibody comprises a heavy chain variable region” and claim 2 recites the limitation “the antibody or antibody fragment according to claim 1, wherein the antibody comprises a light chain variable region”. Claims 11-15, 18, 20, 26, 32, 34-36, and 45-46 recite “the antibody” or “said antibody”. It is unclear if “the antibody” or “said antibody” is referring to the isolated antibody or to the antibody fragment since both encompass “antibody”. Thus, it is further unclear if only the isolated antibody must comprise the listed sequences, as set forth in instant claims 1-2 and 26, or if both the isolated antibody and antibody fragment must comprise the listed sequences. Therefore, the scope of these claims is indefinite.
Claims 16, 41-44, 125, and 127, which depend from the respective claims above, are also indefinite for the same reasons as set forth above.
Note: The Examiner recommends amending the claims to recite “the antibody or antibody fragment” or “said antibody or antibody fragment” to overcome this rejection.
Claims 3, 16, and 26 recite the limitation “an amino acid sequence according to” the respective listed SEQ ID NOs. The “an” makes it unclear if this requires the entire amino acid sequence of the named SEQ ID NO, or if only two consecutive recited amino acids within the sequence of the named SEQ ID NO are required for each of the sequences. Therefore, the scope of this claim is indefinite.
Note: The 112(b) rejection can be overcome by amending the claim to say “the amino acid sequence according to.”
Claims 18, 20, 36, and 42-43 are indefinite as there is no antecedent basis of the amino acid positions being recited. Amino acid numbering is not static or absolute so reference to a base sequence is necessary for antecedent basis of a reference to a position number. The claims should make reference to a particular amino acid sequence (preferably by SEQ ID NO:) in order for the claims to be definite with regard to which position is being referenced.
Claims 45 and 46 recite the limitation of “about” which applicant defines as referring to +/- 10% of the numerical value with which it is used [see page 12, second paragraph of the instant specification]. However, it is unclear in the context of claims 45 and 46 of how “n” can be about 1 to about 8 or about 1 to about 2. Therefore, the scope of these claims is indefinite.
Claim Rejections - 35 USC § 112(a)
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 3, 16, and 26 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.
Claims 3, 16, and 26 recite the limitation “an amino acid sequence according to” the respective listed SEQ ID NOs. It is possible, given the language of the claim which includes "an amino acid sequence” of the respective listed SEQ ID NOs, that any two amino acids in sequence would suffice to meet the limitations of the claims. Because function of any protein, including an antibody, is dependent on the presence of each specific amino acid residue, and with the possibility of added, deleted, or substituted amino acids, a wide variety of antibodies is encompassed by the instant claim. The phrase “an amino acid sequence” allows any fragment, including any two amino acids in sequence, to be encompassed in the instant claim. This would in theory encompass any possible antibody that binds to GUCY2C on earth. These antibodies have no correlation between their structure and function. Amending the claim to recite “the amino acid sequence” would likely overcome the rejection.
The specification teaches anti-GUCY2C antibodies termed mAb#8, mAb#24, mAb#28, mAb#40, and mAb#41 that comprise the amino acid sequences as recited [see pages 18-19 of the instant specification]. However, the specification does not teach a functional antibody comprising anything less than these full recited sequences for each of the six CDRs.
The art recognizes that a complete set of six CDRs comprise the binding region of an antibody (see Sela-Culang et al., 2013; instant PTO-892), and that even a single amino acid change to these regions can completely abrogate the binding specificity of an antibody (see Kussie et al., 1994; instant PTO-892). Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such changes with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held
that:
...To fulfill the written description requirement, a patent specification must
describe an invention and does so in sufficient detail that one skilled in the art can
clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re
Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the
inventor] invented what is claimed."). Thus, an applicant complies with the written
description requirement "by describing the invention, with all its claimed limitations, not
that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention."
Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
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 disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if
the disclosure "indicates that the patentee has invented species sufficient to constitute
the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v.
Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir.
2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus
after only describing a limited number of species because there may be unpredictability
in the results obtained from species other than those specifically enumerated."). "A
patentee will not be deemed to have invented species sufficient to constitute the genus
by virtue of having disclosed a single species when ... the evidence indicates ordinary
artisans could not predict the operability in the invention of any species other than the
one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir.
2004).
Thus, based on the teachings of the instant specification and the art, Applicant has failed to meet the written description of an antibody that binds to GUCY2C that has any two amino acids in each of sequences recited. Therefore, one of skill in the art would not conclude that Applicant was in possession of the antibodies that are able to bind GUCY2C that comprise less than the whole sequences for each of the recited CDR sequences as listed in instant claims 3, 16, and 26.
Claim 12 is 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.
The claim is drawn to the antibody according to claim 1, wherein the antibody is humanized or human antibody.
The claim encompasses human antibodies. However, the specification teaches that the “human antibodies” can be made by the hybridoma method [page 20, third paragraph], which utilizes mice. This is only exemplary and the specification does not provide any example(s) of how the antibodies of the invention are actually produced.
Thus, there is no disclosure of a fully human antibody nor any expectation that a human antibody would comprise the same complementary determining regions (CDRs) as those disclosed in the instant application. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian fibroblast growth factors (FGFs) were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. In the same manner, disclosure of sequences for an antibody without any description of how the specific antibody is produced provides no salient information regarding the sequences produced in a human.
Accordingly, as applicant does not appear to be in possession of a fully human antibody with the claimed sequences, the disclosure as a whole fails to adequately describe a human antibody. Thus, a claim to such an antibody fails to meet the written description requirements.
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 1-3, 11-14, 18, 20, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 12, 15, 20, and 23 of copending Application No. 18/970,285 (‘285; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-3 and 11 of the instant application, claim 1 of the reference application teaches an antibody-drug conjugate (ADC) of Formula (I), claim 10 of the reference application teaches that the antibody is a monoclonal antibody that recognizes and binds a target sequence or epitope of Guanylate Cyclase 2C (GUCY2C), preferably human or cynomolgus Guanylate Cyclase 2C, more preferably human Guanylate Cyclase 2C, claim 12 of the reference application teaches the antibody-drug conjugate of claim 1, wherein the antibody comprises an antigen binding region comprising: an mAb8 light chain variable region (mAb8 VL) complementarity-determining region (CDRL) sequences CDRL 1 of SEQ ID NO: 1, CDRL2 of SEQ ID NO: 2 and CDRL3 of SEQ ID NO: 7 and an mAb8heavy chain variable region (mAb8 VH) CDRH 1 of SEQ ID NO: 4, CDRH2 of SEQ ID NO: 5 and CDRH3 of SEQ ID NO: 6, and claim 15 of the reference application teaches that the antibody comprises an antigen binding region comprising: the mAb8 VL comprises a framework region 1 (FRL 1) of SEQ ID NO: 22, CDRL1 of SEQ ID NO: 1, a FRL2 of SEQ ID NO: 15, CDRL2 of SEQ ID NO: 2, a FRL3 of SEQ ID NO: 23, CDRL3 of SEQ ID NO: 7 and a FRL4 of SEQ ID NO: 24; and the mAb8 VH comprises a framework region 1 (FRH 1) of SEQ ID NO: 18, CDRH1 of SEQ ID NO: 4, a FRH2 of SEQ ID NO: 19, CDRH2 of SEQ ID NO: 5, a FRH3 of SEQ ID NO: 20, CDRH3 of SEQ ID NO: 6 and a FRH4 of SEQ ID NO: 21.
SEQ ID NOs: 1-2 and 7 of the reference application have 100% sequence identity to SEQ ID NOs: 2, 4, and 6 for the CDRL 1-3 of the instant claims, respectively, SEQ ID NOs: 22, 15, 23, and 24 of the reference application have 100% sequence identity to SEQ ID NOs: 1, 3, 5, and 7 for the FRL 1-4 of the instant claims, respectively, SEQ ID NOs: 4-6 have 100% sequence identity to SEQ ID NOs: 34, 36, and 38 for the CDRH 1-3 of the instant claims, respectively, and SEQ ID NOs: 18-21 of the reference application have 100% sequence identity to SEQ ID NOs: 33, 35, 37, and 39 for the FRH 1-4 of the instant claims, respectively.
Thus, the antibody of the reference application anticipates the instantly claimed antibody as elected.
Regarding claims 12-14 of the instant application, claim 20 of the reference application teaches that the antibody is: (a) a humanized or human antibody; and/or (b) an lgG type antibody, preferably an lgG1 antibody; or (c) a recombinant antibody.
Regarding claims 18 and 20, claim 23 of the reference application teaches that the antibody comprises a mAb8-L234A-L235A-D265C heavy chain (i.e. Fc) of SEQ ID NO: 43.
Regarding claim 32, since the sequences for the antibody of the reference application anticipate the instantly claimed antibody, then the reference antibody must necessarily bind to the claimed epitope since function flows from structure. See MPEP 2112.01(II).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 11-16, 18, 20, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 10, 12, 15, 20, and 23 of copending Application No. 18/970,285 (‘285; reference application), as applied to claims 1-3, 11-14, 18, 20, and 32 above, in view of Gilles (US 6,992,174; instant PTO-892).
The teachings of the reference application are above. Further, claim 21 of the reference application teaches that the antibody comprises a Fc region.
However, the reference application does not specifically teach that the antibody comprises a wildtype Fc region and that the Fc region comprises SEQ ID NO: 68.
Regarding claims 15 and 16, Gillies teaches SEQ ID NO: 1, which is the human IgG1 Fc region.
SEQ ID NO: 1 of Gillies has 100% sequence identity to SEQ ID NO: 68 of the instant claim.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Fc region of the reference application to be the Fc region of Gilles. One would have been motivated to use this sequence for the Fc region because it is a known sequence in the art, and it is obvious to use known variations in the prior art for predictable outcomes. See MPEP 2143 (F).
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 11-14, 18, 20, 32, 34-35, 42, 44, 125, and 127 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 10, 12, 15, 20, and 23 of copending Application No. 18/970,285 (‘285; reference application), as applied to claims 1-3, 11-14, 18, 20, and 32 above, in view of Faulstich (WO2010115629; instant PTO-892).
The teachings of the reference application are above.
However, the reference application does not specifically teach that the conjugate comprises at least one toxin and at least one linker connecting the antibody to the toxin and wherein the toxin is an amatoxin.
Regarding claim 34, Faulstich teaches conjugates comprising a toxin and a target-binding moiety, such as an antibody, and wherein the toxin is an amatoxin [see Abstract]. Faulstich further teaches that amatoxin is conjugated to the antibody by linker moieties [see Abstract] and that the conjugates exert their toxic effects to target cells or tissues at much lower concentration so that the conjugates may be administered at lower concentrations and harmful side effects to non-target cells are minimized and can be used to treat therapy resistant or poorly responding tumor types [page 3, lines 24-34].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the conjugate of the reference application to further comprise an amatoxin linked to the antibody, as taught by Faulstich. One would have been motivated to have made this modification with a reasonable expectation of success because Faulstich teaches that this is a known conjugate structure, that the conjugates exert their toxic effects to target cells or tissues at much lower concentration so that the conjugates may be administered at lower concentrations and harmful side effects to non-target cells are minimized and that these conjugates can be used to treat therapy resistant or poorly responding tumor types.
Claim 35 is included in this rejection because Faulstich teaches that if the target-binding moiety (i.e. antibody) comprises free amino, carboxy or sulfhydryl groups, e.g. in the form of Asp, Glu, Arg, Lys, Cys residues, which may be comprised in a polypeptide, then it is preferred that the linker is coupled to such a group. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have picked among the various embodiments of Faulstich to arrive at the claimed embodiment.
Claim 42 is included in this rejection because Faulstich teaches that the linker is connected to the amatoxin via the 6’ C-atom of amatoxin amino acid 4 [page 4, lines 11-14].
Claim 44 is included in this rejection because Faulstich teaches conjugates comprising amanitin Herceptin with a linker at amino acid 4 [see page 35; Section 1.7.1] which is identical to instantly claimed Formula I.
Claim 125 is included in this rejection because Faulstich teaches a pharmaceutical composition comprising the conjugate [page 22, lines 26-29] and claim 26 of the reference application teaches a pharmaceutical composition comprising the antibody-drug conjugate.
Claim 127 is included in this rejection because claim 30 of the reference application teaches administering ipilimumab (anti-CTLA-4), nivolumab (antiPD-1), pembrolizumab (anti-PD-1), and/or atezolizumab (anti-PD-L1) (i.e. immune checkpoint inhibitors) in combination with the antibody-drug conjugate. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the conjugate and the immune checkpoint inhibitor into a single composition since the reference application teaches administering these together. One would have been motivated to have made this modification for ease of administration.
Claims 1-3, 11-14, 18, 20, 32, 34-35, 41-42, 44, 125, and 127 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 10, 12, 15, 20, and 23 of copending Application No. 18/970,285 (‘285; reference application) in view of Faulstich (WO2010115629; instant PTO-892), as applied to claims 1-3, 11-14, 18, 20, 32, 34-35, 42, 44, 125, and 127 above, and further in view of Mondal et al., 2018 (instant PTO-892).
The teachings of the reference application and Faulstich are above.
However, the reference application and Faulstich do not specifically teach that the linker is a Cathepsin B-cleavable linker comprising a di-peptide of Val-Cit.
Regarding claim 41, Mondal teaches that the linker in antibody-drug conjugates is responsible for the connection between the antibody and payload and is a crucial component of ADCs [see Abstract]. Mondal further teaches that one of the most prevalent linkers is the cathepsin B cleavable MC-Val-Cit-PABOH linker [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the linker of Faulstich to specifically be the cathepsin B linker comprising Val-Cit, as taught by Mondal. One would have been motivated to use this linker because it is a known linker in the art for antibody-drug conjugates, and it is obvious to use known variations in the prior art for predictable outcomes. See MPEP 2143 (F).
Conclusion
No claims are allowed.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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