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 .
Claim Status
Claims 2, 20-22, and 25-27 are cancelled. Claims 1, 2-19, and 23-24 as filed on 05 August 2024 are pending and under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2-19, and 23-24 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 references Tables in the claim from the specification. MPEP 2173.05 (s) indicates where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Claims 2-19 and 23-24 depend from claim 1 and incorporate this limitation and are also rejected.
Claims 1, 5-8, and 14 recite the CDRs of antibodies by clone name. The clone name for an antibody does not describe or identify the structure of the antibody. The claim scope is uncertain since the clone name cannot be used to properly identify the product of the claim. The scope of the claims are thus indefinite.
Claim 1 recites “optionally wherein the anti-CD3 antibody or antigen-binding fragment:” before subpart (I) and recites “further optionally” in subparts (I)-(V). The is to a genus of an anti-CD3 antibody or antigen-binding fragment then lists optional limitations that narrow the scope of the claim rendering the claim indefinite. The claim should be amended to either recite the genus and remove the optional language or clearly limit the claim to the requirements following the optional or further optional requirements.
Claim 11 in lines 4-6 and the first line of subparts (1)-(4) and subpart (iii) the applicant recites genus of antibody constant regions followed by optional species of constant regions. It is unclear whether the claim requires the species listed after each recitation of optionally. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species.
Claim 12 recites a genus optionally followed by a species in line 4, 6, and 7. These are to It is unclear whether the claim requires the species listed after each recitation of optionally. In subpart (ii) it is unclear if the claim requires non-human primate CD3 are broadly claimed or is a monkey, cynomolgus or rhesus CD3 species. In subpar (iii) it is unclear if the claim is to a rodent CD3 genus or only to a mouse CD3 specifically. In the final line of the claim it is unclear if the claim is to CD3 or only to the species CD3εδ. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species.
Claim 13 recites the genus of a multispecific antigen binding domain that comprises an anti-CD3 domain and a second antigen binding domain broadly followed by subparts (i)-(viii) which list optional species of multispecific antigen binding domains. It is unclear whether the limits of the species are required by the claim. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species.
Subparts (i)-(viii) of claim 13 also parentheticals and optional species. The use of optional and parentheticals renders the claims indefinite as it is unclear if these are requirements of the claim of merely exemplary.
Claim 13 subpart (vii) contains the trademarks/trade names: “DART”, “BiTE”, and “BEAT”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe: “Dual Affinity Antibody”, “Bispecific T-cell Engage”, and “Bispecific Engaging Antibody”, and, accordingly, the identification/description is indefinite.
Claim 13 subpart (viii) further incorporates multi-specific antibodies in 4 published foreign patent documents. Claims are to be complete in themselves. The multispecific antibodies or antigen-binding domains from the referenced documents are not recited in the claim or the specification of the instant application. Further, these references also incorporate by reference further citations and it is unclear if applicant is incorporating the multispecific antibodies or antigen-binding domains of the 4 documents only or ones also recited by the incorporated references, which also incorporate additional references. The metes and bounds of the claim are indefinite.
Claim 14 subparts (IV)(iii), (V)(iii), (VI) in line 1 and subparts (ii), (VII), (VIII) in line 1 and subpart (ii), and (IX)(ii) recite a genus of biological activity then optional species of biological activity. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species.
Claim 15 recites a genus of nucleic acid encoded VH and VL then provides optional species of VH and VL sequences paired. The claim is indefinite as it is unclear if the species are required limitations or if the genus is being claimed. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species.
Claim 17 subparts (i) and (ii) recite genus of recombinant cells followed by optional species of recombinant cells. It is unclear if the claim is to either the genera of mammalian recombinant cells or non-mammalian recombinant cells or the specific species of these two genera.
Claim 19 recites a method of treating the genus subject then optionally the species of a mammal or non-mammalian vertebrate in subpart (a)(i)-(ii), or the method of treatment can be a method of prevention as it could optionally be administered to a subject at risk of developing the disease in subpart (b). It is unclear whether the claim is a method of treatment for any subject or only to a mammal or non-mammalian vertebrate
Regarding claim subpart (c), the claim is to a method of treatment comprising the antibody or antigen binding domain of the claims which would be a genus of all methods comprising the administration of the antibody or antigen-biding domain, subpart (c) recites an optional species of administering additional agents and further species of adjuvant or a therapeutic agents. This is a genus of methods with optional species of methods.
Regarding the further optional disorders in the last 2 lines of page 35 in claim 19, the claim recites a genus of disease or disorder followed by optional species of diseases. It is unclear if the method of treatment is to all diseases or disorders or only to the recited species. This is repeated with genera of cancer followed by optional species of cancer in subparts (i-1) and (i-2).
The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species for all cited instances.
Claim 24 is to a method of manufacture in a recombinant cell or population of cells, the claim recites optionally the species of in vitro, ex vivo, or in vivo. The claim should be amended to recite the genus and remove the optionally and species language or clearly limit the claims to the species for all cited instances.
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, 2-9, 11-19, and 23-24 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the 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. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Scope of the Claimed Genus
Claim 1 is to an anti-CD3 antibody or antigen-binding fragment. The claim requires one of the listed below:
comprises a CDR of subpart (i) and (ii). These subparts reference tables of the specification making them non-limiting. There is then no sequence limitation on claim 1. The claim also only requires the presence of a single CDR.
An antibody or antigen-binding domain a variable heavy (VH) chain of subpart (A) and a variable light (VL) chain of subpart (B) wherein the VH and VL each comprise at least 1 CDR of variable sequence.
A combination of any CDR sequence previously recited in the claim allowing for variability in the sequences of the CDRs and mixing and matching of the CDRs.
The optional limitations still allow for variability in the number of CDRs, variability in the sequences of the CDRs, and mixing and matching of CDRs of the VH and VL. These non-limiting recitations would not limit the identity of the anti-CD3 antibodies or antigen-binding domains of the claim.
Claims 3-4 requires the presence of a VH comprising 3 CDRs or a VL comprising 3 CDRs.
Claim 5 recites CDRs based on antibody clone name which are non-limiting as described in the 112b rejection.
Claims 6-7 do not provide any limitations for the CDR of the antibodies and antigen-binding domains of the claim. They require the presence of a VH or a VL.
Claim 8 requires the presence of a VH and VL but recites CDRs based on antibody clone name which are non-limiting as described in the 112b rejection.
Claim 9 requires the presence of a VH or a VL with percent identity of required VH or VL sequence which allows for no identity requirement of one variable domain and allows for variation of the CDRs of the required domain sequence.
Claims 11-12 do not further limit the CDRs of the antibodies or antigen-binding domains of the claims.
Claim 13 is to a multi-specific antibody or antigen-binding domain that binds CD3 and comprises a first antigen binding domain comprising a VH or VL polypeptide and a second antigen binding domain.
Claims 14, 16-19, and 23-24 does not provide any limitations for the structure or sequence of antibody or antigen-binding domain.
Claim 15 is a to a nucleic acid encoding an anti-CD3 antibody or antigen binding domain and does not provide any sequence limitations as all are optional. Further, the optional sequence limitations include the presence of either a VH or a VL and percent identity of the sequences.
Summary of Species Disclosed in the original specification
Applicant discloses 23 CD3 binding antibody or antigen-binding domains shown in the table at the end of this rejection. All 23 antigen-binding domains comprise a VH and VL with 3 fully defined CDRs in each variable domain (Tables 1A-B and 2A-B).
State of the Relevant Art
Cluster of differentiation 3 (CD3) is a variant group of proteins that are non-covalently linked to T-cell receptors (Walker) (US 20200190189 A1) (IDS) ([0006]). CD3 comprises four subunits, two zeta subunits, one epsilon subunit, and either a gamma or delta subunit and transduce activation signals to T cells. T-cell receptor signaling leads to T cell activation and IL-2 production and other cytokines ([0008]). CD3 binding antibodies are used in the treatment of multiple diseases including cancer, autoimmune disease ([0280]).
It has been well established in the art that the formation of an intact antigen-binding site in a conventional antibody requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (PTO-892) (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule”, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori. E.g., id., (page 6 ending paragraph onto page 7). But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure of each monoclonal antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). The epitope of an antibody does not provide structure or sequence information about the antibody that binds it.
Further, the skilled artisan has long recognized that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Brown et al., J. Immunol., 156(9):3285- 91 (1996) (PTO-892). Brown teaches that although a single amino acid change in CDR2 of heavy chain of a particular antibody was tolerated, the antibody lost binding upon introduction of two amino acid changes in the same region. Brown, p. 3290 and Tables 1 and 2. Table 1 of Brown shows that even a conservative substitution does not ensure that functionality of the antibody is retained. These older citations are supported my more recent discoveries of why these substitutions change antibody activity. Marvin et. al., Biochemistry, 42(23):7077-7083 (2003) (“Marvin” PTO-892) teaches that changes to the heavy and light chains altered binding affinity (Table 2) with changes to the CDR having large impacts but the changes with the largest impact were from residues in the CDR, but not from ones interfacing with the antigen ( Page 7081 in col 1 “Conclusions and Discussion” and Page 7082 in Figure 4).
This is confirmed by Chiu et al., Antibodies, 8(55):1-80. (2019) (“Chiu” PTO-892). Chiu teaches that the complementarity-determining regions (HCDRs 1-3 and LCDRs 1-3) determine antigen binding requiring specific sequences and orientation of those sequences to properly form tertiary structures that can recognize and bind antigens (Page 4 in 1.2.2 first and last paragraphs and Figure 3). Chiu teaches that antibody modeling with known LCDRs 1-3, HCDR1 and HCDR2 could not predict HCDR3. The field has shown repeatedly over decades that Structure-Based antibody engineering is unable to predict antibody sequences (Page 6 in 1.2.6, Pages 10-11 in Section 2 in particular second paragraph of page 11). Chiu notes the advancement in antibody engineering but notes it is still not possible to predict the point mutations that would improve affinity in both antibodies and multispecific molecules (Page 51 in lines 6-12).
In general, absent at least the conserved structure of the CDRs of the heavy chain and light chain of an antibody, the skilled artisan generally would not be able to visualize or otherwise predict an antibody with a particular set of functional properties would look like structurally. An epitope does not inform one of skill in the art of the structure of the antibody that binds it and a partial structure of variable CDRs or variable heavy or light chains do not provide sufficient information for the CDRs of an antibody.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification discloses 23 CD3 binding antibodies or antigen-binding domains.
The genus of CD3 binding antibodies or antigen-binding domains for use in a method of prevention or treatment of a disease or disorder is a large and variable genus. The disclosure of 23 antibodies or antigen-binding domains is not representative of the genus as changes to the CDRs change the binding activity and each species of antibody would have a unique CDR combination. The disclosure of a set of CDRs of an antibody provides written description for that antibodies and not antibodies with varying CDR sequences.
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. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
As described above the structure in an antibody that provides its binding activity
is the set of 6 CDRs. As changes to the amino acids of the CDRs change its function, the CDRs of the disclosed antibodies do not disclose additional antibodies. The binding activity of an antibody does not provide structure to an antibody. The limitation of binding CD3 or specific biological activity including use in a method of treatment upon binding does not provide any structure to the CDRs that bind them.
Conclusion:
For all of the reasons presented above, one of skill in the art would not know which of the CDR combinations of the claims would meet the structural and functional requirements of the claims either as a product or for use in the method of the claims. The applicant has not provided a representative number of species for all antibodies that bind CD3. The functional structure of an antibody are its 6 CDRs that provide its binding activity based on the sequences of those CDRs, the CDRs of one antibody do not provide one of skill in the art with the functional CDRs of additional antibodies so the variability of the CDRs of the rejected claims mean there is no structure/function correlation, and the disclosed species do not provide written description for additional antibodies. The applicant has shown 23 species of antigen binding domains that bind CD3.
Given the lack of shared structural properties that provide the claimed binding activity, the 23 disclosed species, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention of the claims that includes products and methods of treatment and prevention with the varying sequences of the CDRs.
This rejection could be overcome by limiting the claims to specific combinations
of six CDRs that applicant has shown written description for. Claim 10 is not included in this rejection as it is limited to fully defined VH and VL which comprise fully defined CDRs in the light and heavy chains.
Heavy Chain
Light Chain
SEQ ID NO:
SEQ ID NO:
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3
A001
2112
2114
2116
2122
2124
2126
V002
212
214
216
222
224
226
V003
312
314
316
322
324
326
V004
412
414
416
422
424
426
V005
512
514
516
522
524
526
V006
612
614
616
622
624
626
V007
712
714
716
722
724
726
A002
2212
2214
2216
2222
2224
2226
V008
812
814
816
822
824
826
V009
912
914
916
922
924
926
V010
1012
1014
1016
1022
1024
1026
V011
1112
1114
1116
1122
1124
1126
V012
1212
1214
1216
1222
1224
1226
V013
1312
1314
1316
1322
1324
1326
A003
2312
2314
2316
2322
2324
2326
A004
2412
2414
2416
2422
2424
2426
A005
2512
2514
2516
2522
2524
2526
V014
1412
1414
1416
1422
1424
1426
V015
1512
1514
1516
1522
1524
1526
V016
1612
1614
1616
1622
1624
1626
V017
1712
1714
1716
1722
1724
1726
V018
1812
1814
1816
1822
1824
1826
V019
1912
1914
1916
1922
1924
1926
Claim 19 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 a method of treatment comprising the administration of a CD3 binding antibody or antigen-binding domain, does not reasonably provide enablement for the prevention of a disease by administration of a CD3 binding antibody or antigen-binding domain. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described in In re Colianni, 195 USPQ 150 (CCPA 1977) and have been adopted by the Board of Patent Appeals and Interferences in Ex Parte Forman, 230 USPQ 546 (BPAI 1986). Among these factors are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the breadth of the claims,
5. the amount of direction or guidance present, and
6. the presence or absence of working examples.
The following is an analysis of these factors in relationship to this application.
Guidance/Working Examples
Applicant discloses 23 CD3 binding antibody or antigen-binding domains shown in the table proceeding this rejection. All 23 antigen-binding domains comprise a VH and VL with 3 fully defined CDRs in each variable domain (Tables 1A-B and 2A-B).
Breadth of Claims
Claim 19 is to a method of treatment or prevention of diseases and disorders comprising the administration of variable antibodies and antigen-binding domains that bind CD3.
State of the Art/Predictability
Cluster of differentiation 3 (CD3) is a variant group of proteins that are non-covalently linked to T-cell receptors (Walker) (US 20200190189 A1) (IDS) ([0006]). CD3 comprises four subunits, two zeta subunits, one epsilon subunit, and either a gamma or delta subunit and transduce activation signals to T cells. T-cell receptor signaling leads to T cell activation and IL-2 production and other cytokines ([0008]). CD3 binding antibodies are used in the treatment of multiple diseases including cancer, autoimmune disease ([0280]).
The nature of the invention is such that the composition of the instant claim
must have a therapeutic benefit and be able to prevent cancer from forming in a patient, much like a vaccine. The art teaches that a vaccine must be prophylactic (Stedman's Medical dictionary, 2012, page 11760, in col 1 bullets 9-10)(PTO-892). The specification does not provide any teachings of the prophylaxis of cancers, how to determine the individuals who will develop one or more of the cancers of the claims, nor how to effectively prevent said particular diseases before occurrence. Thus, one of skill in the art would not be able to use the composition of the invention as a preventing vaccine without undertaking to determine how to select for individuals who will develop the diseases before the said disease occurs in the individual. An effective therapeutic protocol for the treatment or prevention of the formation of any disease is subject to a number of factors, which enter the picture beyond simply the administration of the antibody claimed.
It was well known in the art that different antibodies to the same antigen can have different effects following binding of their target antigen. Chan and Carter, Nature Reviews Immunology, 2010; 10:301-316 (PTO-892), summarize these different effects in Figure 2. The five distinct mechanisms include ligand blockade, receptor blockade, receptor downregulation, depletion of cells expressing the target, and signaling induction. The first four mechanisms generally act to inhibit the activity of cells expressing the receptor (or ligand counter receptor). Antibodies that function via these mechanism may broadly be considered antagonist antibodies. Antibodies that induce signals (agonist antibodies), however, may induce either positive or negative signals, depending not only on the nature of the target, but also on other factors such as the developmental state of the cell expressing the target. Chan teaches the administration of antibodies in the treatment of patients with multiple diseases including cancer, but does not teach the use of antibodies as vaccines or prevention. The mechanism of antibodies as therapeutics are inhibition of pathways, antibody-dependent cellular cytotoxicity (ADCC), modulation of T cell function, , and sensitizing cells for chemotherapy (Table 1). The art teaches that it was quickly discovered that antibody therapies results in the development of human anti-chimeric antibodies that bind the therapeutic and limit its half-life and clinical effectiveness (page 305 in col 1 in par 1). As a method of prevention would rely on producing a persistent immune response against a disease before it has formed. An antibody for use in the prevention of cancer is not taught in the art as shown by Chan as antibodies were immediately shown to not persist in a human after administration.
As reviewed in Reichert & Valge-Archer Reichert & Valge-Archer, Nat. Rev. Drug Disc. 2007; 6:349-356 (PTO-892), antibodies can mediate an anti-tumor effect by several different mechanisms. E.g., page 350 "Modes of Action." An antibody conjugated to a cytotoxic agent (an antibody-drug conjugate, or “ADC”) kills the tumor cell by a direct effect, as do radiolabeled antibodies. Id., col. 3. However, such immunoconjugates generally require that the antibody used to deliver the toxin/radiolabel be internalized into the tumor cell; and internalization is a property that is not shared by all antibodies, even among antibodies to the same tumor antigen. Id. at page 351, 1st column. Antibodies can also mediate their effect in an “unmodified” form by activating the immune system, either via ADCC, CDC, or direct induction of apoptosis. Id. at "Immune system activation.” But as the review discusses, not all antibodies have these activities, and ADCC and CDC both depend on the antibody isotype as well as the epitope of the antigen bound. Thus, the skilled artisan understood that the particular epitope targeted by the antibody and the form of the antibody were also determinants of therapeutic activity or lack thereof, even for the same target antigen.
Conclusion
The art teaches that CD3 can be targeted with antibodies or antigen-binding domains for treatment of diseases including cancer and autoimmune disease. The specification shows 23 antibody and antigen-binding domains that bind CD3. But the art does not teach the prevention of any disease or disorder using anti-CD3 binding domains and the application has not shown the administration of the CD3 binding domains in the prevention of disease or disorder.
The specification does not provide any teachings of prevention or vaccination, or how to determine the individuals who will develop diseases or disorders including cancer, nor how to effectively prevent the formation of said disease before occurrence. An effective protocol for prevention of disease and disorders including cancer requires more than simply the administration of the antibody or antigen-binding domain of the claims.
Predicting whether an individual is at risk for developing a disease is a very
unpredictable art. Several factors play a role including, genetic makeup, environmental
factors, age, diet, etc. Therefore, given the unpredictability of prevention and the unpredictability and the broad scope of the claims, undue experimentation would be
required to use the claimed antibody as a method for preventing diseases and disorders.
Claim Rejections - 35 USC § 102
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, 3-8, 11-19, and 23-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walker ‘864 (WO2018208864-A1) (IDS).
Claim 1, 3-8, and 11-19 do not require sequences in the claims.
Regarding claims 1, 13, and 19, Walker ‘864 teaches anti-CD3 antibodies that bind CD3 alone or as multispecific antibodies that work in a method of treating diseases including cancer (abstract, [0025], and ([0028]). Walker ‘864 teaches a multispecific antibody that comprises a first and second binding domain ([0011]), as required by claim 13.
Regarding claims 3-5, Walker ‘864 teaches the antibodies comprise a VH and VL ([0063]) and comprises CDRs in the heavy and light chains (claims 25-26).
Regarding claims 6-8, Walker ‘864 teaches the antibodies comprise a VH and VL ([0063]) and framework regions ([0096]).
Regarding claim 11, Walker ‘864 teaches antibodies that comprise CH1 constant regions ([0143]).
Regarding claim 12, Walker ‘864 teaches the antibodies bind human CD3 ([0158]).
Regarding claim 14, Walker ‘864 teaches the binding of CD3 expressing T cells (abstract, [0282], Example 1) as required by (VIII) of claim 14.
Regarding claims 15-17, Walker ‘864 teaches vectors comprising nucleic acids that encode the CD3 binding domains ([0072]-[0074]) and teaches the vectors transfected into cells ([0136]).
Regarding claim 18, Walker ‘864 teaches a pharmaceutical composition comprising the CD3 binding antibody ([0076]).
Regarding claim 23-24, Walker ‘864 teaches the production of anti-CD3 antibodies by using a vector that comprises a nucleic acid sequence of the antibody in a host cell where the cell is cultured under conditions where the antibody is expressed and then recovering the antibody from the host cell media ([0248] and Example 1).
The CDR combinations that applicant has shown possession of in the table below appear to be free of the art.
Heavy Chain
Light Chain
SEQ ID NO:
SEQ ID NO:
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3
V002
212
214
216
222
224
226
V003
312
314
316
322
324
326
V004
412
414
416
422
424
426
V005
512
514
516
522
524
526
V006
612
614
616
622
624
626
V007
712
714
716
722
724
726
V008
812
814
816
822
824
826
V009
912
914
916
922
924
926
V010
1012
1014
1016
1022
1024
1026
V011
1112
1114
1116
1122
1124
1126
V012
1212
1214
1216
1222
1224
1226
V013
1312
1314
1316
1322
1324
1326
V014
1412
1414
1416
1422
1424
1426
V015
1512
1514
1516
1522
1524
1526
V016
1612
1614
1616
1622
1624
1626
V017
1712
1714
1716
1722
1724
1726
V018
1812
1814
1816
1822
1824
1826
V019
1912
1914
1916
1922
1924
1926
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, 3-8, and 11-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11542330 B2 (PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 3-8, and 11-18 do not require sequences.
Regarding claims 1 and 3-8, the reference patent recites a CD3 binding antibody that comprise VH and VL domains that comprise CDRs and framework regions (claims 1 and 6-7).
Regarding claim 11, the reference patent recites the antibodies comprises an IgG common domain (claim 13).
Regarding claim 12, Figure 4 shows the inherent property of the antibody of the reference patent claims bind human CD3.
Regarding claims 13-14, the reference patent recites a multispecific antibody that binds CD3 and comprises a binding domain for a second antigen binding domain (claims 11-13).
Regarding claims 15-17, the reference patent recites a nucleic acid encoding the antibodies (claim 17) in a vector in a recombinant host cell (claims 18-19).
Regarding claim 18, the references patent recites a pharmaceutical composition that comprises the antibody of the claims (claim 15).
Claims 1, 19, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11542330 B2 (PTO-892) in view of Walker ‘864 (WO2018208864-A1) (IDS).
Claims 1, 19, and 23-24 do not require sequences.
Regarding claim 1, the reference patent recites a CD3 binding antibody that comprise VH and VL domains that comprise CDRs and framework regions (claims 1 and 6-7).
The references patent recites a pharmaceutical composition that comprises the antibody of the claims (claim 15).
The reference patent does not recite a method of treating a disease or a method of producing the antibodies.
These deficiencies are filled by Walker ‘864.
Walker ‘864 teaches anti-CD3 antibodies that bind CD3 alone or as multispecific antibodies that work in a method of treating diseases including cancer (abstract, [0025], and ([0028]).
Walker ‘864 teaches the production of anti-CD3 antibodies by using a vector that comprises a nucleic acid sequence of the antibody in a host cell where the cell is cultured under conditions where the antibody is expressed and then recovering the antibody from the host cell media ([0248] and Example 1).
It would have been obvious at the time the application was filed to combine the pharmaceutical composition of multispecific CD3 binding antibodies of the reference patent with the method of production and method of treatment of Walker ‘864. One of skill in the art would have been motivated to use known in the art methods of producing the antibodies of the reference patents. One of skill in the art would have further been motivated to use the pharmaceutical compositions of the reference patent in a method of treatment as the reference patent is teaching towards use in a method of treatment by producing a pharmaceutical composition. The combination of multispecific antibodies that bind CD3 of the reference patent in the methods of Walker ‘864 would be analogous art. There would have been a reasonable expectation of success as the reference patent teaches the antibodies in pharmaceutical compositions and the knowledge in the art of producing antibodies in recombinant host cells is high.
Claims 1, 3-8, 11-19, and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 7-8, 10-20, 22, and 24-25 of copending Application No. 19122279 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1, 3-8, 11-19, and 23-24 do not require sequences.
Regarding claims 1 and 3-8, the reference application recites a CD3 binding antibody that comprise VH and VL domains that comprise CDRs and framework regions (claims 1-3, 5, and 7).
Regarding claim 11, the reference application recites the antibodies comprise a CH1 domain (claim 13).
Regarding claim 12, the reference application recites that the antibodies bind human CD3 (claim 15).
Regarding claims 13-14, the reference application recites a multispecific antibody that binds CD3 and comprises a binding domain for a second antigen binding domain (claim 14).
Regarding claims 15-17, the reference application recites a nucleic acid encoding the antibodies (claim 16) in a vector (claim 17) in a recombinant host cell (claim 18).
Regarding claim 18, the references application recites a pharmaceutical composition that comprises the antibody of the claims (claim 18).
Regarding claim 19, the reference application recites a method of treating a disease by administering the CD3 binding antibody (claim 20).
Regarding claims 23-24, the reference application recites a method of manufacturing anti-CD3 antibodies by culturing cells that comprise nucleic acids encoding the anti-CD3 antibodies and harvesting and purifying the antibodies (claims 24-25).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claim 10 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643
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