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
1. Applicant’s amendments filed 1/20/23, 10/26/23 and 2/1326 and Applicant’s response filed 7/14/26 are acknowledged and have been entered.
2. Applicant's election without traverse of Group I and species of VH/VL of SEQ ID NO: 10/20, HCDRs SEQ ID NOs: 54, 64 and 74 and LCDRs SEQ ID NOs: 84, 94 and 104, and VH FR SEQ ID NO: 132, 135, 137 and 140 and VL FRs SEQ ID NOs: 142, 144, 146 and 148 in Applicant’s response filed 7/14/26 is acknowledged. Applicant has stated that the antibody comprising the VH/VL of SEQ ID NO: 10/20 is the humanized version of the CFA0305 antibody and is grouped into the Epitope C group.
Claims 1, 2, 8, 11-13, 19, 20, 31 and 35 read on the elected species. Upon consideration of the prior art, search and examination has been extended to include all the recited species.
Accordingly, claim 36 (non-elected species of Group I) and claims 24-29 and 32-34 (non-elected Groups II-IV) are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to non-elected inventions.
Claims 1, 2, 8, 11-13, 15, 19, 20, 31 and 35 are presently being examined.
3. Claim interpretation: The specification discloses that “antibody is used in the broadest sense and encompasses various antibody structures so long as they exhibit the desired antigen binding activity ([0083]). The specification discloses that “affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of an antibody and its antigen and can be represented generally by the dissociation constant (Kd)([0080]). The specification discloses that an antibody that binds to the same epitope as a reference antibody refers to an antibody that blocks binding of the reference antibody to its antigen in a competition assay, or the opposite (i.e., the reference antibody blocks binding to the other antibody) ([0085]). The specification discloses that an “isolated antibody” is one which has been separated from a component of its natural environment (to varying degrees) ([0102]). SEQ ID NO: 39 is the amino acid sequence of an exemplary human wild-type C5 ([0113]). SEQ ID NO: 40 is the sequence of an exemplary beta chain of human C5 ([0113]). The specification discloses that the expression “neutral pH” means a pH of 6.7 to about 10.0, while in particular aspects, it is 7.4 ([0126]); therefore, the definition of neutral pH also encompasses mildly to moderately basic pH. The specification discloses that the expression “acidic pH” means a pH of 4.0 to 6.5 ([0125]).
4. 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.
5. Claims 1, 2, 8, 11-13, 15, 19, 20, 31 and 35 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.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.' " Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2163 I.A.
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." See MPEP 2163 II.3.
Applicant has broadly claimed an isolated antibody that binds to C5/pharmaceutical composition thereof, wherein the antibody binds to an epitope within the beta chain of C5 with a higher affinity at neutral pH than at acidic pH or the antibody binds to C5 and contacts amino acids D51 and K109 of C5 (Seq ID NO: 39), as is recited in instant base claim 1, and including the limitations of the dependent claims.
As such, the recited antibodies must possess the functional properties of binding to an epitope within the beta chain of C5 with a higher affinity at neutral pH than at acidic pH or binding to C5 while contacting amino acid residues D51 and K109 of C5 (SEQ ID NO: 39) (instant base claim 1). Dependent claim 35 also recites the latter contact residues.
In addition, in claim 2, the antibody must also possess the functional property of competing for binding C5 with an antibody comprising a VH/VL from those recited therein, or it must possess the functional property of binding to an epitope within the MG1-MG2 domain of the beta chain of C5, within a fragment consisting of amino acids 33-124 of the said beta chain (SEQ ID NO: 40) of C5, within the beta chain (SEQ ID NO: 40) of C5 which comprises at least one fragment selected from the group consisting of amino acids 47-57, 70-76, and 107-110, within a fragment of the beta chain (SEQ ID NO: 40) of C5 which comprises at least one amino acid selected from the group consisting of E48, D51, H70, H72, K109, and H110, or must bind to the same epitope an antibody described in Tables 2, 7, or 8.
In claim 8, in addition, the antibody must possess the functional property of inhibiting activation of C5 and/or inhibiting activation of C5 variant R885H.
The antibodies of claim 1 that are recited in dependent claims 13 and 15 are also structurally recited as mix and match CDRs and additionally in claim 15, with the FR regions that are mixed and matched. The sequences recited in claims 13 and 15 have some fixed amino acid residues at particular positions in the sequences but also have variable residues at other positions in the same sequences. Also please note that the CDRs and the FRs recited in these claims “comprise” the recited sequences, so the claim language encompasses not CDRs and FRs that consist of the recited sequences but instead also“ comprise CDRs and FRs sequences comprising other non-recited N- and/or-C terminal sequences appended thereto. Also, in claim 13, the antibody need only comprise one of the heavy chain or light chain CDRs but must still possess the requisite functional properties recited in base claim 1. It is the case for claim 15 that depends upon claim 13, that the antibody need only comprise one of the heavy chain CDRs and one of the light chain CDRs (at part “(a)”), only one heavy chain CDR with the recited framework regions (FR1-FR4) (at part “(b)”), only one of the heavy chain CDRs (different from that in part “b”) along with the recited framework regions (FR1-FR4) (at part “(c)”).
The antibody that is recited in dependent claim 19, is recited as having at least 95% sequence identity to particular VH and/or VL fully defined sequences, wherein the 5% difference can be in any portion of the VH and/or VL, including in the CDRs. In the instance of parts “(a)” and “(b)”, only the at least 95% sequence identity VH or only the VL need to be present.
In claim 20, although the VH and VL are fully defined, in the case of parts “(a)” and “(b)”, only the VH or the VL, respectively, need be present.
The specification does not disclose a representative number of species of such isolated antibody, nor sufficient relevant identifying characteristics in the form of structure or functional characteristics coupled with a known or disclosed correlation between structure and function. This is the case for the following reasons.
The antibodies recited in the instant claims encompass any species of animal that can make them or encompasses artificial repertoires of antibodies. The instant specification discloses that the exemplified antibodies were made in rabbits (e.g., Example 2 at [0334]). In the immediate parent application (of which the instant application is a continuing application), it is stated on the record that the specification discloses at least 17 different antibodies that contact amino acid D51 of C5, compete for binding to complement C5, and for which C5 binding is abolished with a D51A C5 variant, with 9 of these antibodies originating from distinct parental sequences that represent a variety of VH and VL sequences having limited sequence similarities. This Examiner would agree for the 9 CFA antibodies disclosed in Table 2. (The antibodies disclosed in Tables 7 and 8 are engineered variants of the lead CFA antibody CFA0305, with Table 7 showing the VH sequences and Table 8 showing the VL sequences, with their respective CDRs of the said 305 variants.) However, as the instant claims encompass any antibody having the recited functional binding properties, these rabbit antibodies do not provide adequate written description for the genus of all such recited antibodies. This speaks to the issue of insufficient representative species for the claimed genus of antibodies.
As Applicant is undoubtedly aware, recent court decisions in the biotechnology arena have highlighted the issue with defining binding members strictly using functional terms as can be readily seen in both AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) and Amgen v. Sanofi. (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim a binding molecule by describing something that is not the invention, i.e., the structure to which it binds, as knowledge of the chemical structure of the thing being bound does not give the required kind of structure-identifying information about the thing being claimed.
It is known in the art that the repertoires of antibodies that bind to a same antigen or epitope from different species are highly diverse, both within the species repertoire and between species (see for example, Lloyd et al. (Protein Engineering, Eng. Design & Selection, 2009, 22(3): 159-168), Edwards et al. (JMB, 2008, 334: 103-118), Poosarla et al. (Biotechn. Bioeng., 2017, 114(6): 1331-1342), Khan and Salunke (J. Immunol, 2014, 192: 5398-5405)). For instance, the CDR repertoires of rabbit and mouse antibodies that bind to the same antigen or epitope are significantly different in their germline genetics, average loop lengths and somatic diversification mechanisms, even when convergent to recognize identical molecular features on a target. In addition, mice diversify their repertoires primarily through VDJ combinatorial joining and random addition/deletion at junctions, whereas rabbit rely heavily on gene conversion using upstream pseudogenes in tandem with very high rates of somatic hypermutation. As well, many rabbit light chains have an extra inter-domain disulfide bond that locks the variable and constant regions, providing rigid thermodynamic stability absent in standard mouse frameworks, which could potentially influence affinity of binding and overall conformation of CDRs. (See for example, Banik et al. (MABS, 2023, 15(1), 2273018, pages 1-14), Kodangattil et al. (mAbs, 2014, 6:3: 628-636), Popkov et al. JMB, 2003, 325: 325-335)). These considerations evidence that one of skill in the art could not readily envision the sequences of the antibodies having the recited functional binding properties, including ones that bind to a same epitope. (As for the antibodies that must possess the functional property of competing for binding to C5 with one of the recited antibodies, the specification discloses that an antibody that binds to the same epitope as a reference antibody refers to an antibody that blocks binding of the reference antibody to its antigen in a competition assay, or the converse ([0085])).
The recitation of the antigen to which an antibody binds, or the subregion or epitope of the antigen to which an antibody binds, or the recitation of competing with a reference antibody, does not provide the structure (vis-à-vis, the cognate CDRs of an antibody that provide most of the binding interaction with the antigen) of the antibody and hence does not provide adequate written description for the genus of such antibodies.
As regards the VH/VL sequences having at least 95% sequence identity to fully defined amino acid sequences (claim 19), the claim encompasses changes in CDR regions as well as in FR regions. It has been known for quite some time that even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA 1982 Vol 79 pages 1979-1983).
In addition, in claims 19 and 20, the VH or the VL need only be present. In the case of antibodies comprising at least one of the VH or VL regions, or in the case of claims 13 and 15 wherein only one CDR need be present, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. One of skill in the art could not readily envision the sequence of other CDRs, VHs or VLs that can be comprised within the antibody possessing only one of the recited CDRs, VHs, or VLs.
Also as is enunciated above, in claims 13 and 15, the CDRs and/or FRs are mix and match and the CDR sequences have multiple possible substituent amino acid residues at certain positions therein. As the art teaches that even minor changes in the amino acid sequences of an antibody, and particularly in the CDRs can affect the functional properties of antigen binding and/or binding affinity, one of skill in the art could not readily envision which substituent CDRs could be present in tandem with others, and with the mix and match FRs, in order that the functional properties are retained.
Therefore, it appears that the instant specification does not adequately disclose the breadth of the isolated antibody recited in the instant claims. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all such antibodies at the time the instant application was filed.
6. Claims 13,15, 19 and 20 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
“To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In re Wright, 999F2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)). In In re Wands 8 USPQ2d 1400 (CAFC 1988), a number of factors are set forth which a court may consider in determining whether a disclosure would require undue experimentation. These factors were set forth as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. All the factors need not be reviewed when determining whether a disclosure is enabling. Amgen, Inc. v. Chugai Pharm. Co., Ltd., 927F2.d 1200, 1213, 18 USPQ2d 1016, 1027 (Fed. Cir. 1991) (noting that the Wands factors “are illustrative, not mandatory. What is relevant depends upon the facts.”).
The specification does not disclose how to make and use the instant invention, an isolated antibody that binds to C5/pharmaceutical composition thereof, wherein the antibody binds to an epitope within the beta chain of C5 with a higher affinity at neutral pH than at acidic pH or the antibody binds to C5 and contacts amino acids D51 and K109 of C5 (SEQ ID NO: 39),wherein the antibody comprises any one of the components recited in claims 13,15, 19 or 20.
The specification has not enabled the breadth of the claimed invention because the claims encompass an antibody in which only one defined heavy chain CDR, only one defined light chain CDR, only one defined VH region, or only one defined VL region is present in the antibody, and additionally for claim 19 in which the VH and/or VL sequences have at least 95% sequence identity to one of the recited sequences, wherein the changes can be anywhere in the sequence, including in a CDR.
The state of the art is such that it is unpredictable in the absence of appropriate evidence whether the claimed compositions can be made and/or used without undue experimentation.
In claim 13, the antibody need only comprise one of the heavy chain or light chain CDRs. It is the case for claim 15 that depends upon claim 13, that the antibody need only comprise one of the heavy chain CDRs and one of the light chain CDRs (at part “(a)”), only one heavy chain CDR with the recited framework regions (FR1-FR4) (at part “(b)”), only one of the heavy chain CDRs (different from that in part “b”) along with the recited framework regions (FR1-FR4) (at part “(c)”). In claims 19 and 20, only one of the VH or the VL need be present. The antibody recited in dependent claim 19, is also recited as having at least 95% sequence identity to particular VH and/or VL fully defined sequences, wherein the 5% difference can be in any portion of the VH or VL, including in the CDRs. In the instance of parts “(a)” and “(b)”, only the at least 95% sequence identity VH or only the VL need to be present.
Regarding the Wands factors and the state of the art, the skilled artisan was aware that it is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. It has been known for quite some time that even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA 1982 Vol 79 pages 1979-1983).
For example, evidentiary reference D’Angelo et al. (Front. Immunol. 2018, 9, article 395, pages 1-13) teaches that “the same HCCDR3 can be generated by many different rearrangements, but that specific target binding is an outcome of unique rearrangements and VL pairing: the HCDR3 is necessary, albeit insufficient for specific antibody binding” (see entire reference, especially abstract).
De Pascalis et al. (The Journal of Immunology (2002), 169: 3076-3084) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.).
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (BBRC, 2003, 307: 198-205) who constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.).
Holm et al. (Molecular Immunol. 2007, 44, 1075-1084) describes the mapping of an anti-cytokeratin antibody where although residues in the CDR3 of the heavy chain were involved in antigen binding while a residue in CDR2 of the light chain was also involved (abstract).
Although the specification discloses fully defined antibodies that bind D51 and K109 of C5 (SEQ ID NO: 39), it would be unpredictable which other cognate CDRs except for these cognate CDRs present in the disclosed fully defined antibodies, and including which other VH or VLs could pair with only one CDR, only one VH, or only one VL and retain binding to the recited residues of C5 or binds to the beta chain of C5 with higher affinity at neutral pH than at acidic pH. The working examples are not commensurate with the claims, and undue experimentation would be necessitated to make such antibodies.
There is insufficient guidance in the specification as to how to make and/or use the instant invention. Undue experimentation would be required of one skilled in the art to practice the instant invention. See In re Wands 8 USPQ2d 1400 (CAFC 1988).
7. 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.
8. Claims 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is indefinite in the recitation at part “(v)” of “that is the same epitope as an antibody described in Tables 2, 7, or 8”, i.e., claim 2 is indefinite because it incorporates by reference to Tables 2, 7, or 8. Claims must 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 duplication 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) (citations omitted). (See MPEP 2173.05(s) “Reference to Figures or Tables [R-10.2019]”).
9. 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.
10. For the purpose of prior art rejections, the filing date of the instant claims 2, 8, 13, 15, 19 and 20 is deemed to be the filing date of the 17/974,350 application, i.e.,12/18/15 as JP 2014-257647 does not support the claimed limitations of the instant application. The said JP application does not provide support for: the fragment recited at part “(iii)” of claim 2, the same epitope as an antibody described in Table 7 or 8 at part “(v)” of claim 2 (the JP application only has support for variant 305LOS, whereas Tables 7 or 8 of the instant application disclose a multiplicity of additional 305 variants), nor the C5 variant R885H recited in claim 8, nor the CDRs and mixes thereof recited in claims 13 and 15, nor the VH and VL recited in claims 19 and 20 except for SEQ ID NO: 10/20 which are those of 305LOS (that is, SEQ ID NO: 106-110 are VH of additional 305 variants and SEQ ID NO: 111-113 are VL of additional 305 variants disclosed in Tables 7 and 8 of the instant application).
For the purpose of prior art rejections, the filing date of the instant claims 1, 11, 12, 31 and 35 is deemed to be the filing date of the said JP 2014-257647 application, i.e.,12/19/14.
11. 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)(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.
12. Claims 2, 8, 13, 15, 19 and 20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2017064615 A1 as evidenced by admissions in the specification at Tables 7 and 8, [0391] and [0021].
WO 2017064615 A1 teaches anti-C5-inhibiting antibodies and pharmaceutical composition thereof that are identical to those disclosed in Tables 7 and 8 of the instant application that are variants of the 305 antibody, i.e., 305LO5, 305LO15, 305LO16, 305LO18, 305LO19, 305LO20, 305LO22, and 305LO23 (see for example Table 1 of the art reference spanning pages 16-20). The admissions in the specification at Tables 7 and 8 are also the sequences of the VH/VL and corresponding CDRs. Please note that SEQ ID NO: 10/20 of the art reference are identical to the VH/VL of instantly recited SEQ ID NO: 10/20, respectively, while instantly recited SEQ ID NO: 106-110 (VH sequences) and SEQ ID NO: 111-113 (corresponding VL sequences) are identical to the remaining 305 variants disclosed in the said tables. See entire reference. Also please note that the FR sequences recited in instant claim 15 are comprised within the art antibody sequences. The admissions in the specification at [0391] and [0021] are that the 305 variants bind wild type C5 (human C5, SEQ ID NO: 39) and contact amino acid residues D51 and K109 of said C5 and bind to C5 with a higher affinity at pH 7.4 (neutral pH) than at pH 5.8 (acidic pH).
13. 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.
14. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 18/181,641 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 1, 2, 8, 11-13, 15, 19, 31 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15, 18-23, 26 and 27 of 18/181,641, as evidenced by admissions in the instant specification at [0057], [0064], [0368], and [0391].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 18/181,641 are drawn to a method for treating a C5-related disease comprising administering an anti-CD5 antibody (i.e., a pharmaceutical composition thereof) comprising a VH comprising the sequence of SEQ ID NO: 2 and a VL comprising the sequence of SEQ ID NO: 6.
SEQ ID NO: 2 of ‘641 is identical to instantly recited SEQ ID NO: 106 and SEQ ID NO: 6 of ‘641 is identical to instantly recited SEQ ID NO: 111 (i.e., they are the VH/VL of the 305LO15 variant antibody). Please also note that the FR regions comprised in the 305LO15 antibody are identical to instantly recited SEQ ID NO: 133, 135, 138 and 140 for the variable heavy chain region.
The admissions in the instant specification at [0391] and [0057] are that the antibodies of the 305 antibody series bind to D51 and K109 of human C5 and inhibit activation by C5 (e.g., [0057]). The admission in the instant specification at [0064] is that the 305 variant antibody inhibits activation of both C5 and R885H variant of C5. The admission in the instant specification at [0368] is that antibody 305LO15 is humanized (and therefore chimeric).
15. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 18/905,654 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 1, 2, 8, 11-13, 15, 19, 31 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of 18/905,654, as evidenced by admissions in the specification of ‘654 at the table spanning pages 46-47 and admissions in the instant specification at Tables 7 and 8, [0057], [0368], and [0391].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 18/905,654 are drawn to a method of treating GBS comprising administering an anti-C5 antibody, including wherein the antibody is crovalimab. The specification of 18/905,654 evidences that the VH/VL of the antibody are represented by SEQ ID NO: 3/5 and are the VH/VL of antibody 305LO15 (pages 46-47 at the table). The specification of 18/905,654 also evidences that the entire antibody comprises a modified human IgG1 constant heavy chain domain variant and the antibody also comprises a human light chain constant domain (ibid).
Instantly recited SEQ ID NO: 106 is 100% identical to SEQ ID NO: 3 of ‘654 and instantly recited SEQ ID NO: 111 is 100% identical to SEQ ID NO: 5 of ‘654 (see the instant specification at Tables 7 and 8 at the second entries thereof). The instant specification discloses that the 305LO15 antibody is a variant of the 305 antibody. The admission in the instant specification at [0391] is that the antibodies of the 305 antibody series bind to D51 and K109 of human C5, and inhibit activation by C5 (e.g., [0057]). Please also note that the FR regions comprised in the 305LO15 antibody are identical to instantly recited SEQ ID NO: 133, 135, 138 and 140 for the variable heavy chain region. The admission in the instant specification at [0368] is that antibody 305LO15 is humanized (and therefore chimeric).
16. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 18/905,476 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 1, 2, 8, 11-13, 15, 19, 31 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of 18/905,476 as evidenced by admissions in the specification of 18/905,476 at the Table spanning pages 47-48, and admissions in the instant specification at [0057], [0386], Tables 7 and 8, and [0391].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 18/905,476 are drawn to a method of treating GBS in a subject comprising administering an anti-C5 antibody (a pharmaceutical composition thereof) that is crovalimab.
The specification of 18/905,476 evidences that the VH/VL of the antibody are represented by SEQ ID NO: 3/5 and are the VH/VL of antibody 305LO15 (pages 47-48 at the table). The specification of 18/905,654 also evidences that the entire antibody comprises a modified human IgG1 constant heavy chain domain variant and the antibody also comprises a human light chain constant domain (ibid).
Instantly recited SEQ ID NO: 106 is 100% identical to SEQ ID NO: 3 of 18/905,476 and instantly recited SEQ ID NO: 111 is 100% identical to SEQ ID NO: 5 of 18/905,476 (see the instant specification at Tables 7 and 8 at the second entries thereof). The instant specification discloses that the 305LO15 antibody is a variant of the 305 antibody (Tables 7 and 8). The admission in the instant specification at [0391] is that the antibodies of the 305 antibody series bind to D51 and K109 of human C5, and inhibit activation by C5 (e.g., [0057]). Please also note that the FR regions comprised in the 305LO15 antibody are identical to instantly recited SEQ ID NO: 133, 135, 138 and 140 for the variable heavy chain region. The admission in the instant specification at [0368] is that antibody 305LO15 is humanized (and therefore chimeric).
17. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/263,691 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 1, 2, 8, 11-13, 15, 19, 31 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 60-77 of copending Application No. 17/263,691, as evidenced by admissions in the instant specification at Tables 7 and 8, [0057], [0368] and [0391].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 17/263,691 are drawn to a method for treating a C5-related disease or condition associated with excessive or uncontrolled activation of C5 in a subject comprising administering to a human subject a dose of an anti-C5 antibody, wherein the antibody has the same CDRs as those present in antibody 305L015 that is listed in the instant specification at Tables 7 and 8 (i.e., SEQ ID NO: 3-5 and 7-9 of ‘691 are identical to instant SEQ ID NO: 117, 118, 121-123 and 125, respectively). The instant specification discloses that the 305LO15 antibody is a variant of the 305 antibody. The admission in the instant specification at [0391] is that the antibodies of the 305 antibody series bind to D51 and K109 of human C5, and inhibit activation by C5 (e.g., [0057]]). The admission in the instant specification at [0368] is that antibody 305LO15 is humanized (and therefore chimeric).
18. Claims 1, 2, 8, 11-13, 15, 19, 31 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-66 of U.S. Patent No.9,765,135.
Although the claims at issue are not identical, they are not patentably distinct from each other because the isolated antibody/pharmaceutical composition thereof of the claims of ‘135 are species of the instant generic claims (1, 11, 12, 31 and 35), the antibody recited at part “(j)” of instant dependent claim 2, and the antibody recited in dependent claim 8. In addition, while instant dependent claim 13 only requires that one of the recited CDRs be present (by the recitation of “or”), the claims of ‘135 recite all of the limitations recited in that instant claim. While instant dependent claim 15 only requires a subset of CDRs and FRs recited therein, the claims of ‘135 recite all such sequences. While the antibody recited in dependent claim 19 only requires a VH having at least 95% sequence identity to the recited sequences (at part a), or a VL sequence having at least 95% sequence identity to the amino acid sequences recited therein (at part b), or a mix or match VH/VL sequence having at least 95% sequence identity to the sequences recited therein (at part c), the claims of ‘135 recite VH/VL pairs 100% identical to those recited in instant claim 19. The same can be said for instant dependent claim 20, with the exception that the same VH/VL both must be required at part “c” of claim 20.
The sequences recited in the claims of ‘135 are identical to those recited in the instant claims and in the instant specification and are antibodies that are in the 305 antibody series. The admission in the instant specification at [0391] is that the antibodies of the 305 antibody series bind to D51 and K109 of human C5 and inhibit activation by C5 (e.g., [0057]]).
19. Applicant is advised that a double patenting rejection is not being made over the claims of application serial no. 17/630,046 because the said application does not have an applicant or an inventor in common with the instant application. However, the Applicant of the instant application is a subsidiary controlled by the Applicant of 17/630,046. Should Applicant revise the instant application to add the Applicant of the 17/630,046 application, a double patenting rejection will be made and will not be considered to be a new ground of rejection (i.e., the claims of 17/630,046 are drawn to a method of treating a C5-related disease in a subject comprising administering an anti-C5 antibody that is crovalimab that corresponds to antibody 305LO15, as is enunciated above in this office action). The same is the case for the claims of application serial no. 17/630,050.
20. No claim is allowed.
21. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights