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 1-9, 12 and 15 are pending and will be examined on the merits.
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 3, 7-8 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3, 8 and 15
Regarding claims 3, 8 and 15, each recitation of the phrase "preferably" (as well as “more preferably” in claim 15 only) independently renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Note: for examination, limitations indicated as being “preferable” will be interpreted as not being required to satisfy the claim.
Claim 7
Regarding claim 7, the claim lacks a conjunction (“and”, “or”, etc…) between list element (a) and list element (b). This renders the metes and bounds of the claim unclear and thus the claim indefinite because it is unclear if claim 7 requires either (a) or (b) OR both (a) and (b) to be satisfied.
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 isolated anti-human PDL1 antibody comprising HC CDRs and LC CDRs selected from specific sequences identified by SEQ ID NO. Claim 2 attempts to further limit claim 1 and recites that the antibody of claim 1 is a fully human antibody. Claim 2 does not contain all the limitations of claim 1 because all of the antibodies of the present disclosure are murine chimeric (e.g., p 37, line 6) or humanized (e.g., p 42, line 2), meaning all of the CDR sequences recited in claim 2 are murine CDRs. Claim 2 does not contain all of the limitations of claim 1 because claim 2 recites “fully human antibody” but claim 1 does not recite any fully human CDR sequences.
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.
Claim 8 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 8 is dependent on claim 1. Claim 1 recites an isolated anti-human PDL1 antibody comprising HC CDRs and LC CDRs selected from specific sequences identified by SEQ ID NO. Claim 2 attempts to further limit claim 1 and recites that the antibody or antigen binding fragment of claim 1 is a camelid antibody. A camelid antibody is a functional antibody fragment derived from camels, alpacas and llamas that comprise a VH chain with three VH CDRs only. Claim 8 does not contain all of the limitations of claim 1 because claim 1 does not recite any camel, alpaca or llama-derived VH CDRs known to be suitable for use in single domain antibodies.
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 1-9, 12 and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for 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 and description in specification
Scope of claimed antibodies
All of the claims are directed to an isolated anti-human PDL1 antibody or antigen-binding fragment thereof and, as such, all of the claims are directed to an antibody or antibody fragment capable of performing the recited function of binding to human PDL1. With respect to the antibody structure required to perform the recited function of binding human PDL1, the current claim set encompasses several genera of antibody, both with respect to the amino acid composition of antibody complimentary determining regions (CDRs) as well as antibody framework regions (FR).
Claim 1-3, 8-9, 12 and 15
Claims 1-3, 8-9, 12 and 15 contain the antibody structural limitation pertinent to antigen binding that are recited instant claim 1 and, as such, are directed antibodies capable of performing the recited function of binding human PDL1 and comprising a LCVR and/or a HCVR, wherein the LCVR comprises LCDR1, LCDR2 and LCDR 3 of SEQ ID NOs: 20, 21 and 22, respectively and wherein the HCVR comprises HCDR1 of SEQ ID NO: 23, a HCDR3 of SEQ ID NO: 25 and a HCDR2 that is at least 94% identical to any one of SEQ ID NOs: 24, 45, 46 or 47. As such, claim 1 is directed to antibodies capable of performing the recited function of binding human PDL1 and comprising four possible combinations of distinct and complete HCDR triplets (all triplets recited in order HCDR1, HCDR2 and HCDR3, respectively): 1) SEQ ID NOs: 23, 24 and 25, 2) SEQ ID NOs: 23, 45 and 25, 3) SEQ ID NOs: 23, 46 and 26 and 4) SEQ ID NOs: 23, 47 and 26.
In addition to encompassing multiple distinct and complete CDR triplets, all of SEQ ID NOs: 24 and 45-47 are seventeen amino acid sequences and “at least 94% identical to” of a 17 amino acid parental sequence is the same as saying the parental sequence with up to one amino acid substituted anywhere. Claim 1 also provides no guidance or preference regarding which amino acids may be substituted out and which amino acids are permitted to be substituted in. As such, claim 1 is also directed to antibodies capable of performing the recited function of binding human PDL1 and comprising HCDR2s comprising any one of SEQ ID NOs 24, 45, 46 or 47 with up to one amino acid of the parental sequence substituted for any other amino acid.
In addition, the “or” element of the “and/or” conjunction recited with respect to the HCVR and LCVR in claim 1 means that an antibody only needs to comprise either the LCDR or HCDR sequences of claim 1 in order to satisfy claim 1. As such, claim 1 is also directed to 1) antibodies comprising LCDR1, LCDR2 and LCDR 3 of SEQ ID NOs: 20, 21 and 22, respectively paired with any HCVR (or none at all), with the resulting antibody being capable of performing the recited function of binding human PDL1 and 2) antibodies comprising HCDR1 of SEQ ID NO: 23, a HCDR3 of SEQ ID NO: 25 and a HCDR2 that is at least 94% identical to any one of SEQ ID NOs: 24, 45, 46 or 47 paired with paired with any LCVR (or none at all), with the resulting antibody being capable of performing the recited function of binding human PDL1.
Claims 4 and 6-7
Claims 4, 6 and 7 are all directly or indirectly dependent on claim 1 and recite several selections of complete HCVR and LCVR sequences with respect to antibody structure.
Claim 4 is directed to an antibody comprising a LCVR of SEQ ID NO:18 and/or a HCVR of SEQ ID NO: 19.
Claim 6 is directed to an antibody selected from: 1) an antibody comprising LCVR of SEQ ID NO: 38 and/or HCVR selected from SEQ ID NOs: 30-37, 2) an antibody comprising LCVR of SEQ ID NO: 39 and/or HCVR selected from SEQ ID NOs: 30-37 or 48-50 and 3) an antibody comprising LCVR of SEQ ID NO: 44 and/or HCVR selected from SEQ ID NOs: 40-43 or 51-53.
Claim 7 is directed to an antibody selected from: 1) an antibody comprising LCVR of SEQ ID NO: 39 and/or HCVR selected from SEQ ID NOs: 36 or 48-50 or 2) an antibody comprising LCVR of SEQ ID NO: 44 and/or HCVR selected from SEQ ID NOs: 41 or 51-53.
All of claims 4, 6 and 7 contain the “and/or” conjunction between the recited LCVRs and HCVRs and, as such, all of claims 4, 6 and 7 are also directed to antibodies comprising only one of the recited LCVR or HCVR sequences paired with any complementary LCVR or HCVR (or none at all) provided the resultant antibody possesses the required function of binding human PDL1.
Claim 5
Claim 5 is dependent on claim 1 and further limits claim 1 by reciting structural limitations regarding the antibody framework regions. Claim 5 breaks the heavy and light chain framework regions into four components each: 1) heavy chains FR = FR-H1, FR-H2, FR-H3 and FR-H4 and 2) light chains FR = FR-L1, FR-L2, FR-L3 and FR-L4.
With respect to the FR-light chain regions, claim 5 recites that FR-L1, FR-L3 and FR-L4 are SEQ ID NOs: 54, 56 and 57, respectively and FR-L2 is SEQ ID NO: 55 or SEQ ID NO: 55 with one or more of: 1) the second amino acid substituted with I, 2) the 3rd substituted with H and/or 3) the 9th substituted with S.
With respect to the FR-light chain regions, claim 5 recites that: 1) FR-H4 is SEQ ID NO: 61, 2) FR-H1 is SEQ ID NO: 58 or SEQ ID NO 58 with the first amino acid substituted for E and/or the 23rd substituted with T, 3) FR-H2 is SEQ ID NO: 59 with or without the 13th amino acid substituted with I and 4) FR-H3 is SEQ ID NO: 60 or SEQ ID NO: 60 substituted with one or more of: the 2nd amino acid substituted with A, the 8th substituted with T, the 11th substituted with N and/or the 31st substituted with G.
Antibodies of the Disclosure
The present disclosure discloses a total of 27 distinct antibodies in Table 8, with each antibody comprising a HCVR and LCVR and capable of performing the recited function of binding human PDL1 on p 44-45 of the instant Specification, which is replicated below:
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815
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127
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Please note that the point mutations to the framework regions recited in claim 5 are accounted for in SEQ ID NOs: 38, 39 and 44 for the LC and SEQ ID NOs: 30-37 and 40-43 of the LC (Specification, p 42, lines 10-20). Please also note that all of the anti-PDL1 antibodies recited above are also derived from the same murine chimeric antibody (HCVR and LCVR of SEQ ID NOs: 19 and 18, respectively) (Specification, p 42, line 1-45, line 30) and, as such, contain the same parental murine VH and VL CDR sequences except for HCDR2 (Specification, p 42, line 15-30). The instant disclosure teaches that the parental HCDR2 is instant SEQ ID NO: 24 and that the variant HCDR2s of SEQ ID NOs: 45, 46 and 47 (all recited in claim 1; HCDR2 of SEQ ID NO 45 is in HCVR of SEQ ID NO: 48; HCDR2 of SEQ ID NO 46 is in HCVR of SEQ ID NO: 49; HCDR2 of SEQ ID NO 47 is in HCVR of SEQ ID NO: 50) were generated and shown to bind PDL1 in order to avoid a possible deamidation NG site in HCDR2 (Specification, p 42, line 16-24). The instant disclosure does not provide any examples of any of the recited HCVRs paired with any other LCVRs with the resultant antibody capable of performing the required function of binding human PDL1. The instant disclosure does not provide any examples of any of the recited LCVRs paired with any other HCVRs with the resultant antibody capable of performing the required function of binding human PDL1. The instant disclosure does not provide any examples of any single domain antibody (e.g., HCVR or LCVR only) capable of performing the required function of binding human PDL1.
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, providing structural support that allows the CDRs to adopt the right conformation to form the antigen binding site (Sela-Culang, p 7, ¶ 5). 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).
In addition, at the time of filing, it was known that there are many conventional anti-PDL1 antibodies disclosed in the prior art and that they are comprised of six CDR sequences. Furthermore, Marasco (Marasco, et al.., US 2015/0274835 A1; Published 10/1/2015; Priority to 3/13/2013 via US 61/779,969) discloses multiple anti-PDL1 antibodies and all of these antibodies comprise 6 distinct CDRs with known amino acid sequences (Marasco, claim 1).
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.
While all of the explicitly defined VH and VL CDRs recited in instant claim 1 as well all of the explicitly defined FR sequences of instant claim 5 are reflected in the antibodies of the disclosure and are shown to form antibodies capable of performing the required function of binding human PDL1, the indeterminate pairing of recited HCVRs with undisclosed (and possibly unknown) LCVRs (and vice versa) permitted by the claims as well as the unrestricted substitution of one amino acid in HCDR2 (recited in claim 1) result in the claimed genera being far larger and more variant than the disclosure can provide support for.
Regarding the unrestricted substitution of one amino acid in HCDR2 recited in claim 1, HCDR2 is a 17-residue sequence, meaning there are 17 possible sites to pick for substitution. Once a site is picked, there are 19 amino acids available for substituting in. As such, there are 323 possible HCDR2 variants encompassed by the claims. As stated above, the instant disclosure teaches SEQ ID NO: 24 as the parental murine HCDR2 and SEQ ID NOs: 45-47 as one amino acid variant HCDR2s capable of performing the recited function of binding human PDL1 when paired with the remaining recited VH and VL CDRs. A disclosure of 4 species is not sufficient to be representative of 323.
The genus encompassed by the indeterminate pairing of recited HCVR or LCVR with an unrecited, complementary LCVR or HCVR is a far greater number that is likely not possible to calculate accurately. This genus includes all antibodies that comprise one of the recited HCVR or LCVR paired with any complementary domain, provided the resultant antibody is capable of performing the required function of binding human PDL1. This genus includes pairings of a recited HCVR or LCVR paired with complementary domains that are unknown and/or have not yet been discovered. A disclosure of 27 antibodies encompassing a four possible distinct pairings of six CDRs is nowhere near sufficient to be representative of such an astronomically large genus.
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, an antibody is often defined in terms of the epitope that it binds and there is currently no way of predicting the CDR sequence required to bind an antigen and mediate internalization. There is nothing in the instant Specification that would supplant these notions and, as such, the is no structure/function correlation that would allow a skilled artisan to envision which, if any, CDR combinations encompassed by the instant claims would form a functional antibody with the required function of binding human PDL1 other than the combinations present in antibodies specifically disclosed in the instant Specification.
Because the species disclosed are insufficient to be considered representative of any the genus of all antibodies with the recited function of binding human PDL1 coupled with the lack of established structure/function correlation, claims 1-9, 12 and 15 lack written description and Applicant was not in possession of the invention as claimed.
Claim 15 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating a tumor, does not reasonably provide enablement for methods of preventing a tumor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The instant claims are drawn to a method for treating or preventing a PDL1-mediated diseases that are tumors in a subject, said method comprising administering to said subject a composition comprising the instant claimed PDL1 antibodies.
The Merriam-Webster definition of the word “prevent”—“to keep from happening or existing”. Thus, the broadest reasonable interpretation of the claim is that the method comprising the administration of the instant claimed PDL1 antibodies prophylactically prevents cancer from occurring by killing every cancer cell present or stopping every healthy cell from becoming cancerous.
The skilled artisan recognized that before any method of preventing a particular cancer could be practiced with any level of predictability, some method of identifying subjects predisposed to the particular cancer must be available. While the art has advanced in recent years, it is still highly unpredictable not only which individuals will develop a particular cancer, but also when a “preventative” therapy will be helpful.
Breast cancer illustrates the difficulties associated with detecting and preventing cancer. The skilled artisan generally recognized symptoms of breast cancer to include changes in the breast such as the presence of a lump, nipple discharge, or other changes in the shape or texture of the breast. However, such symptoms are non-specific and have multiple other potential causes. Even detection of a breast mass by mammography is only an early step in the diagnosis of breast cancer. As noted in a 2014 article in the World Journal of Clinical Oncology, following an abnormal mammographic finding exam, biopsy is required for a diagnosis (cancer vs. benign lesion) and staging is required to determine appropriate treatment (Shah, et al.World J Clin Oncol 2014 August 10; 5(3): 283-298).
Further, even in individuals judged to have a twofold increased risk of developing breast cancer, prevention with tamoxifen was incomplete. Briefly, high risk women were given either tamoxifen or a placebo and the occurrence of breast cancer was monitored for 20 years. The placebo group had a breast cancer rate of 12.3% and the treatment group had a breast cancer rate of 7.8 %. (Cuzick, et al Lancet Oncol 2015 Jan; 16(1) 67-75). While tamoxifen did reduce the risk of the occurrence of breast cancer, it did not completely prevent it. It should be noted that the Specification is not enabling for prevention of any type of cancer.
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, 5-9, 12 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 19-20 and 27-29 of copending Application No. 18/260,435 (Published as US-20240034801-A1 on 2/1/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are directed to a bispecific antibody comprising a PDL1 binding domain with the same CDR sequences.
Regarding instant claim 1, copending claim 1 is directed to anti-PDL1 antibodies comprising the same set of six distinct CDRs (Copending claim 1). Regarding instant claim 3, copending claim 11 is directed to antibodies comprising immunoglobin G constant regions. Regarding claims 6-7, copending claim 13 is directed to a VH of copending SEQ ID NO: 6 (same as instant SEQ ID NO: 41) and VL sequence of copending SEQ ID NOs: 2 (same as instant SEQ ID NO: 44). Regarding instant claim 2, as evidenced by the instant Specification, instant SEQ ID NO: 41 is a humanized VH sequence (Specification, p 43, table 7, entry 13) and instant SEQ ID NO: 44 is a humanized VL sequence (Specification, p 43, table 7, entry 3), thus making the antibody of the ‘436 application a humanized antibody.
Regarding instant claim 5, the VH and VL sequences of the ‘435 application (copending SEQ ID NOs: 6 and 2, respectively) are reproduced below with the framework regions underlined and with explanations regarding which, if any, of the permissible amino acid substitutions recited in instant claim 5 are made:
VL of ‘435 application (Copending SEQ ID NO: 2)
DIQMTQSPSSLSASVGDRVTITCKASQDVHTAVAWIQQKPGKSPKLLIYSASNRYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQHYITPLTFGQGTKLEIK
FRL1 = instant SEQ ID NO: 54
FRL2 = instant SEQ ID NO: 55 with 2nd amino acid Y substituted with L
FRL3 = instant SEQ ID NO: 56
FRL4 = instant SEQ ID NO: 57
VH of ‘435 application (Copending SEQ ID NO: 6)
EVQLVQSGAEVKKPGSSVKVSCKASGFNIEDTYIHWVRQAPGQGLEWMGRIDPANANTKYDPKFQGRVTITADTSTNTAYMELSSLRSEDTAVYYCGRGLGAWFAWGQGTLVTVSS
FRH1 = instant SEQ ID NO: 58 with first amino acid Q substituted with E
FRH2 = instant SEQ ID NO: 59
FRH3 = instant SEQ ID NO: 60 with 8th amino acid E substituted with T and 31st amino acid A substituted with G
FRH3 = instant SEQ ID NO: 61
Regarding instant claim 8, copending claim 10 is directed to scFv and Fab antigen binding fragments. Regarding instant claim 12, copending claim 19 is directed to compositions comprising the antibody of the ‘435 application and a pharmaceutically acceptable carrier. Regarding instant claim 9, copending claim 14 is directed to nucleic acids encoding the antibodies of the ‘435 application. Regarding instant claim 15, copending claims 27-29 are directed to methods of treating gastric cancer, said method comprising administering the antibody of the ‘435 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-9, 12 and 15 are rejected.
No claims are allowed.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643