Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Status
Applicant’s amendment filed November 5, 2024 has been received and entered.
Claims 2, 7, 12, 14-15, 19-21, 23, 25, 29, 32-34, and 36-37 have been amended.
Claims 3-6, 8-11, 13, 16, 22, 24, 26-28, 35, and 38-42 have been canceled.
Claims 1-2, 7, 12, 14-15, 17-21, 23, 25, 29-34, and 36-37 are pending and under consideration.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2022/013735 filed January 25, 2022, which claims the benefit of U.S. Provisional Application 63/141,703 filed January 26, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 25, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 7, and 17 are objected to because of the following informalities:
Claim 1 recites the term “complementary”, however, should read “complementarity”.
Claims 1, 7, and 17 recite the phrase “a LCDR”, however, it should read “an LCDR”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 15 and 21 recite the “the Fc polypeptide comprises amino acid substitutions L234A and L235A and/or the amino acid substitution N297A”.
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However, antibodies utilize various numbering schemes to facilitate comparison and analysis. The most commonly used schemes include IMGT, EU, and Kabat. These schemes differ in their approach to defining regions that are crucial for antigen binding and immunogenicity. In particular, the different constant domain identification methods may often designate critical amino acids in the CH1, CH2, or CH3, regions with different position numbers, indicating that the constant region is not well defined. For example, the excerpt of the IGMT Scientific chart (https://www.imgt.org/IMGTScientificChart/Numbering/Hu_IGHGnber.html; 5 March 2026) demonstrates the variability in the A-strand of the Fc region when different numbering schemes are used. Similar variability is observed for the other domains of the Fc region.
Further, claims 15 and 21 depend from claims 14 and 20, respectively, which recite the amino acid sequence of the Fc region is selected from SEQ ID NOs: 47-50, or an amino acid sequence that is at least 90% identical to SEQ ID NOs: 47-50. However, without a numbering scheme, the exact positions of the L234A and L235A and/or N297A amino acid substitutions cannot be determined. This is compounded when factoring amino acid sequences with at least 90% identity, wherein the variability can occur anywhere in the Fc region. Additionally, Fc polypeptide sequences SEQ ID NOs: 47-50 are 217 amino acids in length, making it impossible to determine what residues of SEQ ID NOs: 47-50 correspond to L234, L235, or N297.
Claim Rejections - 35 USC § 112
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.
Written Description
Claims 1-2, 7, 12, 14-15, 18-21, 23, 25, 29-34, and 36-37 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.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP § 2163.
Claim 1 is drawn to an isolated antibody that specifically binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to av3b, wherein the isolated antibody comprises an HCDR1 having a sequence of any one of SEQ ID NOS: 1, 5, and 6; an HCDR2 having a sequence of any one of SEQ ID NOS: 2, 4, and 7; an HCDR3 having the sequence of SEQ ID NO: 3; an LCDR1 having a sequence of any one of SEQ ID NOS: 8, 11, 13, and 14; an LCDR2 having a sequence of any one of SEQ ID NOS: 9 and 12; and an LCDR3 having the sequence of SEQ ID NO: 10.
It should also be noted that SEQ ID NO: 2 contains a variable residue at position 3. The specification does not specify what amino acids are acceptable substitutions for position 3 of SEQ ID NO: 2, therefore it is interpreted that position 3 of SEQ ID NO: 2 can be any of the 20 naturally occurring amino acids.
Therefore, the claims encompasses a large genus of structurally distinct polypeptides.
Although, claim 2 recites the specific amino acid sequences (SEQ ID NOs) of the HCDR regions for embodiments (a) through (e), it still allows for multiple combination of LCDRs as recited in claim 1. Similarly, claim 7 defines the LCDRs for the anti-human integrin b8, but allows for multiple combinations of HCDR amino acid sequences from those recited in claim 1.
Claim 12 further recites that the antibody heavy chain and light chain variable regions are at least 90% identical to SEQ ID NOs: 15-19 and SEQ ID NOs: 20-25, respectively.
Claims 18-19 recite the amino acid sequences of the heavy chain and light chain variable regions of the antibody recited in instant claim 17 are at least 90% identical to SEQ ID NOs: 16 and 22, respectively. However, the claims or specification do not specify the type (i.e. substitution, deletion, insertion) or location within the heavy chain and/or light chain variable regions the variation can occur.
Therefore, it can be considered that the inventions defined by claims 1-2, 7, 12, and 18-19 encompass a large number of possible variants.
Claims 14 and 20 are drawn to the amino acid sequences of the claimed antibody Fc regions, wherein the Fc comprises a sequence at least 90% identity to SEQ ID NOs: 47-50. However, no guidance is provided in the claims or the specification as to the type (i.e. substitution, deletion, insertion) or location within the Fc region such variation may occur.
There are hundreds of possible combinations of HCDR and LCDR amino acid sequences when only considering the selection of the specific amino acid sequences as described in claim 1. However, the instant specification discloses the amino acid sequence of eleven anti-integrin b8 variants [Table 1] and only provides results for two (ADWA-11 and ADWA-16).
The state of the art at the time of filing understands that integrin-mediated TGFb activation plays a key role in modulating tissue fibrosis, acute lung injury, and pulmonary emphysema. However, a significant knowledge gap remains in the understanding of the mechanism that allows integrin avb8 activate TGFb signals on nearby cells [0004] (WO 2014/165524; cited IDS 7/25/2023).
It is well understood in the art that protein folding and formulation are complex and fairly unpredictable processes, in such that substituting even one amino acid within the sequence can change the structure and function of said protein. Thus, one cannot readily extrapolate the properties of an antibody defined by its CDRs (e.g., ADWA-11 and ADWA-16) to other possible sets of antibodies encompassed by claim 1, as the properties of the protein having an amino acid sequence of antibodies ADWA-11 and ADWA-16 are not predictive of the full genus of proteins that can be generated.
For example, Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) discloses the results of TGFb activation studies and latency associated peptide (LAP) adhesion blocking experiments for nine variants designated ADWA-2, ADWA-8, ADWA-10, ADWA-11, ADWA-13, ADWA-15, ADWA-16, ADWA-20, and ADWA-25. The results show that ADWA-2, ADWA-16, ADWA-15, ADWA-11, ADWA-13,and ADWA-10 are more effective for blocking LAP adhesion and inhibiting TGFb activation, while the remaining three antibodies demonstrate little or no effect [Figs. 9-13].
The instant application has not provided a sufficient description showing possession of the necessary 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 genus of polypeptides encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. § 112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 48 USPQ2d 1398 (Fed Cir. 1997)).
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 Vas-Cath, p. 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, p. 1116). Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., Inc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in
“possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support
need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein
v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning —
i.e., what the written description and knowledge in the art would lead one to speculate as to
modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also
ensures that when a patent claims a genus by function, the specification recites sufficient materials to
accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3.
Given the claimed broadly class of polypeptides, in the absence of sufficient disclosure of relevant
identifying characteristics, the patentee must establish “a reasonable structure-function correlation”
either within the specification or by reference to the knowledge of one skilled in the art with functional
claims. There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed polypeptides to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Claims 15, 21, 23, 25, 29-34, and 36-37 are included in the rejection because they depend from or otherwise require all the limitations of a rejected independent claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 7, 12, 23, 25, 29-31, and 33-34 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) (“Sheppard”). This reference qualifies as prior art under both 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
The instant claims are drawn to an isolated antibody that specifically binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to av3b, wherein the isolated antibody comprises an HCDR1 having a sequence of any one of SEQ ID NOS: 1, 5, and 6; an HCDR2 having a sequence of any one of SEQ ID NOS: 2, 4, and 7; an HCDR3 having the sequence of SEQ ID NO: 3; an LCDR1 having a sequence of any one of SEQ ID NOS: 8, 11, 13, and 14; an LCDR2 having a sequence of any one of SEQ ID NOS: 9 and 12; and an LCDR3 having the sequence of SEQ ID NO: 10, wherein the antibody comprises an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 2, an HCDR3 of SEQ ID NO: 3, an LCDR1 of SEQ ID NO: 14, an LCDR2 of SEQ ID NO: 9, and an LCDR3 of SEQ ID NO: 10. Further comprising a heavy chain variable region having at least 90% identity to any one of SEQ ID NOs: 15-19 and/or a light chain having at least 90% identity to any one of SEQ ID NOs 20-25, wherein the antibody is humanized, cross-reacts with mouse integrin b8, and/or blocks TGF3 activation, and/or antagonizes binding of LAP to avb8 with an IC50 below 5 nM. Also claimed is an isolated nucleic acid encoding the isolated antibody, an expression vector comprising the nucleic acid, an isolated host cell comprising the vector; a method of reducing TGFb activation in a human in need thereof, the method comprising administering a therapeutically effective amount of the isolated antibody, wherein the human has asthma, multiple sclerosis or acute lung injury, rheumatoid arthritis, psoriasis, and chronic obstructive pulmonary disease and at least one symptom of the disease is ameliorated by the reduced TGFb activation.
Sheppard discloses an isolated antibody that specifically binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to avb8 [claim 1], wherein the antibody comprises the complementarity determining regions (CDR1, CDR2, and CDR3) of the heavy and light chain variable regions of an antibody selected from the group including SEQ ID NO: 1 and SEQ ID NO: 16, respectively [claim 7] (instant claims 1, 2, and 7, and 12). The isolated antibody comprises one or more human framework regions [claim 8] (instant claim 23), cross-reacts with mouse integrin b8 [claim 2], blocks TGFb activation [claim 3], and antagonizes the binding of LAP to avb8 with an IC50 below 5 nm [claim 4] (instant claim 25).
Sheppard further discloses an isolated nucleic acid encoding the antibody [claim 10] (instant claim 29), an expression vector comprising the nucleic acid [claim 11] (instant claim 30), an isolated host cell comprising the vector [claim 12] (instant claim 31).
Also disclosed is a method of reducing TGFb activation in a human in need thereof, the method comprising administering a sufficient amount of the antibody, thereby reducing TGFb activation in the human [claim 13] (instant claim 33), wherein the human has a disease selected from asthma, multiple sclerosis, acute lung injury [claim 14], rheumatoid arthritis, psoriasis, and chronic obstructive pulmonary disease and at least one symptom of the disease is ameliorated by the reduced TGFb activation [claim 15] (instant claim 34).
Sheppard discloses the identical antibody (ADWA16) recited in the instant claims, comprising the heavy and light chain variable amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 16, respectively. These amino acid sequences are 100% identical to the instantly claimed VH and VL amino acid sequences of SEQ ID NO: 18 and SEQ ID NO: 25, respectively (instant claim 12).
The VH amino acid sequence (SEQ ID NO: 1) taught by Sheppard comprises the presently claimed amino acid sequences for the HCDR1 (SEQ ID NO: 6), HCDR2 (SEQ ID NO: 2), and HCDR3 (SEQ ID NO: 3) regions (instant claims 1, 2).
The VL amino acid sequence (SEQ ID NO: 16) taught by Sheppard comprises the presently claimed amino acid sequences for the LCDR1 (SEQ ID NO: 14), LCDR2 (SEQ ID NO: 9), and LCDR3 (SEQ ID NO: 10) regions (instant claims 1, 7).
Therefore, absent a showing of any difference, the product disclosed by the prior art is deemed to anticipate the claimed product.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) (“Sheppard”).
The instant claims are drawn to an isolated antibody that specifically binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to av3b, wherein the isolated antibody comprises an HCDR1 having a sequence of any one of SEQ ID NOS: 1, 5, and 6; an HCDR2 having a sequence of any one of SEQ ID NOS: 2, 4, and 7; an HCDR3 having the sequence of SEQ ID NO: 3; an LCDR1 having a sequence of any one of SEQ ID NOS: 8, 11, 13, and 14; an LCDR2 having a sequence of any one of SEQ ID NOS: 9 and 12; and an LCDR3 having the sequence of SEQ ID NO: 10; a pharmaceutical composition comprising the isolated antibody and a pharmaceutically acceptable carrier.
The teachings of Sheppard are set forth above.
In addition Sheppard teaches a pharmaceutical composition comprising the antibody [claim 9], which may comprise a pharmaceutically acceptable carrier [0091].
It would have been obvious to include a pharmaceutically acceptable carrier in the pharmaceutical composition, as this is common practice to the ordinary artisan when formulating antibodies for administration. Thus, the prior art reference provided a prima facie case of obviousness for the instant invention.
Claims 14-15 and 36-37 are rejected under 35 U.S.C. 103 as being unpatentable over Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) (“Sheppard”) as applied to claims 1-2, 7, 12, 23, 25, and 29-34 above, and further in view of Niessen et al. (WO 2020/051333) (“Niessen”)
The instant claims are drawn to an isolated antibody that specifically binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to av3b, wherein the isolated antibody comprises an HCDR1 having a sequence of any one of SEQ ID NOS: 1, 5, and 6; an HCDR2 having a sequence of any one of SEQ ID NOS: 2, 4, and 7; an HCDR3 having the sequence of SEQ ID NO: 3; an LCDR1 having a sequence of any one of SEQ ID NOS: 8, 11, 13, and 14; an LCDR2 having a sequence of any one of SEQ ID NOS: 9 and 12; and an LCDR3 having the sequence of SEQ ID NO: 10; wherein he antibody comprises an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOS: 47-50, and wherein the Fc polypeptide comprises amino acid substitutions L234A and L235A and/or the amino acid substitution N297A. Also claimed is a method of treating a cancer in a human, the method comprising administering to the human a therapeutically effective amount of the isolated antibody, wherein the cancer is a metastatic cancer and/or a solid tumor cancer.
The teachings of Sheppard are set forth above.
Sheppard does not teach amino acid sequences of the Fc regions of the anti-human integrin b8 antibodies, or that the antibodies can be used in methods to treat cancer.
Niessen teaches methods of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of an anti-avb8 antibody [pg. 57, E184; instant claim 36]. The cancer can be a solid tumor or a metastatic cancer [pg. 62, E207, E210; instant claim 37]. Niessen carried out multiple experiments showing antibody ADWA11 is efficacious in multiple solid tumor models and induces persistent anti-tumor activity [pg. 237-238].
Niessen teaches preferably, the anti-avb8 antibody has at least one amino acid substitution compared to a native sequence Fc region [pg. 108] and more preferably, comprises a human IgG1 Fc region comprising a substitution at one or more positions selected from L234A, L235A, and G237A, as numbered according to the Eu numbering scheme [pg. 25, E69; instant clam 15].
Niessen discloses the amino acid sequences of several IgG1 constant regions that were used to generate the anti-avb8 antibodies, including SEQ ID NO: 181.
SEQ ID NO: 181 (Db) shares 98.6% identity to the native Fc amino acid sequence of SEQ ID NO: 47 (Qy) recited in the instant claims as shown below [instant claim 14]. SEQ ID NO: 47 comprises the native residues L234 and L235 (red box) of the IgG1 Fc region. As shown below, SEQ ID NO: 181 has been mutated using alanine substitution to silence effector function at positions 234 and 235 [instant claim 15]. Niessen teaches “effector functions" refer to biological activities attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, down regulation of cell surface receptors, and B cell activation [pg. 110].
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The full sequence of SEQ ID NO: 181 is shown below. Residues A234, A235, and N297 are underlined.
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The teachings of Sheppard differ from the present invention in that although anti-avb8 antibodies that reduce TGFb activation are taught, the antibody is not explicitly taught as being useful for the treatment of cancer and the Fc region amino acid sequences are not taught. Given that Niessen teaches anti-avb8 antibodies for the treatment of various cancers by blocking deleterious TGFb activation, the skilled artisan would have a reasonable expectation of success in treating cancer using the antibodies taught by Sheppard for the same purpose. A skilled artisan would also be motivated to incorporate various amino acid substitutions into the antibody Fc region as these are known to alter effector function as evidenced by Niessen [pg. 86]. Thus, the combination of prior art references provided a prima facie case of obviousness.
Nonstatutory Double Patenting
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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 1-2, 7, 12, 14-15, 17-21, 23, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 12-15, 17-21, and 23-25 of copending Application No. 18/274,118.
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the identical anti-human integrin b8 antibodies comprising the identical amino acid sequences and SEQ ID NOs with the same limitations and physical properties as recited in the instant claims.
The copending claims differ from the instant claims in that they are directed to a method of treatment, versus the instant claims that are directed to the antibody itself. However, a method comprising a recited product anticipates the product. Thus, the instant claims are anticipated by the claims of the copending application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 29-31, and 33-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 12-15, 17-21, and 23-25 of copending Application No. 18/274,118 in view of Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) (“Sheppard”).
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the identical anti-human integrin b8 antibodies comprising the identical amino acid sequences and SEQ ID NOs with the same limitations and physical properties as recited in the instant claims.
The copending claims differ from the instant claims in that they do not teach a nucleic acid encoding the antibody, an expression vector comprising the nucleic acid, a host cell comprising the nucleic acid, a pharmaceutical composition comprising the antibody, a method of reducing TFGb activation in a patient with asthma, multiple sclerosis or acute lung injury, rheumatoid arthritis, psoriasis, or chronic obstructive pulmonary disease and at least one symptom of the disease is ameliorated by the reduced TFGb activation.
Sheppard teaches an isolated antibody that binds to human integrin b8 and inhibits adhesion of latency associated peptide (LAP) to avb8 having the identical amino acid sequence as the antibody recited in the instant claims. Sheppard also teaches an isolated nucleic acid encoding the antibody [claim 10], an expression vector comprising the nucleic acid [claim 11]. Sheppard also teaches a method of reducing TFGb activation in a human in need thereof, comprising administering the antibody, thereby reducing TFGb activation in the human [claim 13], wherein the disease is selected from asthma, multiple sclerosis or acute lung injury, rheumatoid arthritis, psoriasis, or chronic obstructive pulmonary disease and at least one symptom of the disease is ameliorated by the reduced TFGb activation [claims 14-15]. Thus, the instant claims are anticipated by the claims of the copending application in view of Sheppard.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 12-15, 17-21, and 23-25 of copending Application No. 18/274,118 in view of Sheppard et al. (WO 2014/165524; cited IDS 7/25/2023) (“Sheppard”).
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the identical anti-human integrin b8 antibodies comprising the identical amino acid sequences and SEQ ID NOs with the same limitations and physical properties as recited in the instant claims.
The copending claims differ from the instant claims in that they do not teach a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier.
The teachings of Sheppard are set forth above.
In addition, Sheppard teaches a pharmaceutical composition comprising the antibody [claim 9], which may comprise a pharmaceutically acceptable carrier [0091].
It is common practice to include a pharmaceutical carrier when formulating a pharmaceutical composition. Thus, the instant claims are rendered obvious by the claims of the copending application in view of Sheppard.
This is a provisional nonstatutory double patenting rejection.
Claims 14-15 and 36-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 12-15, 17-21, and 23-25 of copending Application No. 18/274,118 in view of Niessen et al. (WO 2020/051333) (“Niessen”)
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the identical anti-human integrin b8 antibodies comprising the identical amino acid sequences and SEQ ID NOs with the same limitations and physical properties as recited in the instant claims.
The copending claims differ from the instant claims in that they do not teach the amino acid sequence the antibody Fc region of the anti-human integrin b8 antibodies, or that the antibodies can be used in methods to treat cancer.
The teaching so Niessen have been set forth above.
Specifically, Niessen teaches methods of treating cancer, including solid tumors and metastatic cancers by administering an anti-avb8 antibody. Niessen also teaches the anti-avb8 antibody comprises a human IgG1 Fc region and the amino acid sequence (SEQ ID NO: 181) comprises L234A and L235A substitutions. Given that Niessen teaches anti-avb8 antibodies for the treatment of various cancers by blocking deleterious TGFb activation, the skilled artisan would have a reasonable expectation of success in treating cancer using the antibodies taught by the copending claims for the same purpose. A skilled artisan would also be motivated to incorporate various amino acid substitutions into the antibody Fc region as these are known to alter effector function as evidenced by Niessen. Thus, the instant claims are rendered obvious by the claims of the copending application in view of Niessen.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642