Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 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.
DETAILED ACTION
This action is in response to claim amendments filed 5/10/23. Claims 67-86 are pending and under examination.
Drawings
The drawings are objected to because the drawings have been submitted in color with no corresponding petition to accept color drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 86 is objected to because of the following informalities: “accessing” should be “assessing”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 67, 71-74, 78-81, and 85-86 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 67, 74, and 81 are directed to methods of treating frontotemporal dementia (FTD) using any antibody that binds a particular artificial peptide (tau sequence) with a particular equilibrium constant and that binds a tau fragment but does not bind to full length htau40. As such, the claim is directed to an antibody defined entirely by function (what it binds and what it does not bind). See MPEP §2163(I)(A) which states:
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
In this case, antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody. However, there is no way to a priori look at an antigen sequence (certain SEQ ID NOs) and envisage the combination of six CDRs that will bind that antigen, much less an antibody which binds that antigen only when it is fragmented from the full-length protein it is natively found in (htau40) or to a certain specificity (KD).
First, even highly related CDRs may not bind the same target. See for example Kussie (IDS 5/10/23 citation A104) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11). The antibodies were also claimed based on a koff rate determined by surface plasmon resonance, yet the Court stated “when a patent claims a genus using functional language to define a desired result, ‘the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus’”. The Court determined that Abbvie only described one type of structurally similar antibodies which are not representative of the full variety or scope of the genus as they were all derived from a single antibody and were highly structurally similar.
Thus, the art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. As a further example, see Chen (IDS 5/10/23 citation A103) which demonstrates single amino acid changes in the VH CDR2 sequence can increase binding, decrease binding, destroy binding, or have no effect on binding when compared to the wild-type antibody.
Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions.
The specification discloses TauC3. However, as discussed above, without any way to determine the breadth of the claimed genus, there is no way to determine if that antibody represents the full breadth of what is claimed. The disclosure of specific antibodies would not convey to the artisan that Applicant was in possession of the full genus of all antibodies which possess the required functions nor does it allow the skilled artisan to envisage the specific structure of such antibodies. The 200 antibodies of Abbvie only described “one type of structurally similar antibodies which are not representative of the full variety or scope of the genus” according to the Court and so the same conclusion must be reached when provided only a single antibody as in the instant specification.
Further note the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. MPEP 2163 states “disclosure of an antigen fully characterized by its structure…does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional”. While there is ample description of the antigen, this does not correlate to any particular description of the antibody which binds that antigen nor the various properties that antibody must have. The specification lacks the corresponding antibody structure responsible for these properties because structures other than that of TauC3 may still have those properties similar to how the Centocor antibodies had the same properties of the Abbvie antibodies despite being structurally distinct. Further, a single antibody is not representative of the broad and varied genus now claimed.
The claims also encompass those antibodies which bind homologous sequences. In this case, the antibodies are not even defined by the identity of that which they bind. Tau fragments are set forth (SEQ ID NOs: 78-86) yet a homolog, under an ordinary definition as understood by the skilled artisan, is a sequence that is somehow related to these sequences (e.g., via divergent evolution or amino acid substitution). The antibodies must therefore bind a sequence which is neither claimed nor described. No examples of any sequences “homologous” to these peptides is provided in the specification. Nothing in the specification suggests that Applicant was in possession of the identity of these homologs, much less all antibodies which bind all homologous sequences but not htau40 as well as, when binding an amino acid sequence which is not native to humans (e.g., tau from another species), must still be therapeutic when applied to a human having FTD with no evidence or requirement that binding to a homolog would still allow binding to human tau fragments. The specification does not convey possession of these homologous sequences nor possession of the antibodies which bind them.
Therefore, claims 67, 71-74, 78-81, and 85-86 fail to meet the written description requirement. Claims limited to TauC3 are not included in this rejection because TauC3 is a structurally defined antibody. Moreover, the binding properties of TauC3 are inherent to that structure and so other terms such as the “homologous” peptides need not be described, as every step of the method could be practiced and the binding requirements are directed to the properties of the antibody itself.
Double Patenting
Claims 67-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10894822. Although the claims at issue are not identical, they are not patentably distinct from each other because every limitation of the instant claims is found in the reference claims, the difference being in the disease to be treated. The reference claims are directed to using the same antibody to treat “other tauopathy” (claim 4). As defined by the reference specification, “tauopathy” includes FTD (C15). As such, the instant claims are covered by and an obvious variation of the reference claims. See Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999), Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998), and In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970) for support in using the specification to establish the definition of claimed terms.
Claims 67-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of U.S. Patent No. 8703137. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are directed to using the same antibody to treat “other tauopathy” (claims 8 and 14). As defined by the reference specification, “tauopathy” includes FTD (C14). See above rejection for support in using the specification to establish the definition of claim terms.
Claims 67-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11673944 in view of New York (US 20100316564; IDS 5/10/23 citation A55).
The instant claims and the reference claims contain the same limitations: same antibody (TauC3), with the same properties, inclusion of a diluent, IV infusion, slowing progression of a disease, etc. The only difference is that the reference application is drawn to treatment of progressive supranuclear palsy (PSP) while the instant claims are directed to treatment of FTD.
However, the reference claims claim the antibody binds abnormal tau truncated at the D421 residue. New York teaches antibodies recognizing immunogenic tau peptides effective in preventing and treating frontotemporal dementia and progressive supranuclear palsy (paragraph 31, 33; claim 8), promoting the clearance of aggregates from the brain of a subject, and slowing the progression of a tau-pathology related behavioral phenotype in a subject (paragraphs 7-9). New York teaches such an immunogenic peptide includes SEQ ID NO: 101 (HLSNVSSTGSIDMVD), corresponding to residues 407-421 (paragraph 10). New York indicates this peptide is particularly preferred as the cleavage at aspartate 421 correlates with animal models of tauopathy (paragraph 54). New York indicates that this peptide can be used to generate an antibody specific for the free end of a D421 fragment on the C-terminus but which would not facilitate removal of normal tau (paragraph 54). New York teaches “subject” includes humans (e.g., paragraphs 50, 73, and 82-83). New York teaches direct administration of the antibody to patients suffering tauopathies (paragraphs 84-86), of which both FTD and PSP are explicitly named within this genus (paragraph 31).
It would have been obvious to one of ordinary skill in the art at the time of filing to modify the method of the reference patent to treat FTD rather than PSP. This is because the reference claims articulate that the TauC3 antibody binds the cleaved D421 residue of tau and New York teaches similar antibodies that also function by binding D421 as well as teaching that this therapy is expected to work for both PSP and FTD.
Allowable Subject Matter
The Examiner recognizes co-pending application 16/838467. These claims appear to be drawn to an anti-TauC3 antibody rather than the TauC3 antibody itself. As such, no double patenting rejection is made at this time.
There is no art rejection in this Office Action.
The closest prior art is that of New York (US 20100316564; IDS 5/10/23 citation A55). New York teaches antibodies recognizing immunogenic tau peptides effective in preventing and treating frontotemporal dementia (paragraph 31, 33; claim 8), promoting the clearance of aggregates from the brain of a subject, and slowing the progression of a tau-pathology related behavioral phenotype in a subject (paragraphs 7-9). New York teaches such an immunogenic peptide includes SEQ ID NO: 101 (HLSNVSSTGSIDMVD), corresponding to residues 407-421 (paragraph 10). New York indicates this peptide is particularly preferred as the cleavage at aspartate 421 correlates with animal models of tauopathy (paragraph 54). New York indicates that this peptide can be used to generate an antibody specific for the free end of a D421 fragment on the C-terminus but which would not facilitate removal of normal tau (paragraph 54). New York teaches “subject” includes humans (e.g., paragraphs 50, 73, and 82-83). New York teaches direct administration of the antibody to patients suffering tauopathies (paragraphs 84-86), of which FTD is explicitly named within this genus (paragraph 31). New York teaches the immunogenic peptides can be varied (paragraphs 40-41). New York does not teach administration of antibodies binding one of the claimed sequences.
Thus, New York provides a starting peptide (15-mer) and notes the critical residue to be preserved is the C-terminal D421. New York also provides motivation to vary the length of the epitope to generate other D421 specific antibodies.
However, the state of the art establishes that the length of the epitope is critical for such end-specific antibodies.
Saido 1992 (IDS 5/10/23 citation A80) teaches generating end-specific antibodies (p.82, C1). Saido 1992 states "the length of the immunogenic peptide is critical for production of the autolysed [cleaved] form-specific antibody" (p.83, C1).
Saido 1993 (IDS 5/10/23 citation A81) teaches antigenic 5-mers produce end-specific antibodies (p.25239, C2). While this provides motivation to use peptides shorter than those of New York, this is accompanied by the statement “because the newly formed amino group at the N-terminus of the proteolytic product seems to constitute an essential part of the epitope” (p.25240 C1).
US 20020086847, paragraph 34 (IDS 5/10/23 citation A92) teaches that, while longer lengths of epitopes “in some instances have been used successfully”, shorter peptides are better. However, ‘847 states specifically that a length of five (5) amino acids for “any given peptide…ensures that the specific free amino group at the N-terminus constitutes an essential part of the epitope recognized by the new antibody” (paragraph 34).
Taking the evidence as a whole, one of ordinary skill in the art at the time of the invention would have been motivated to use antibodies directed to varying sized peptides of New York in order to slow the progression of a symptom of FTD in a human subject. However, while the 15-mer of New York was successful, US2002086847 suggests these longer peptides are successful “in some instances”. The art above (Saido 1992, Saido 1993, ‘847) teach that the length of the peptide is critical for success and that while shorter peptides are more successful, the location of the amino group of the epitope is important to the binding properties of newly generated antibody.
The only difference between New York and the instant claims is that New York teaches HLSNVSSTGSIDMVD (SEQ ID NO: 101) is a preferred immunogenic peptide to generate end-specific antibodies that bind D421 but not full length tau, while the instant claims are drawn to shorter peptides used for the same purpose, such as instant SEQ ID NO: 80 (STGSIDMVD) and SEQ ID NO: 86 (SSTGSIDMVD). Thus, the difference is the peptide of New York is a 15-mer (tau 407-421) while the instant peptides are shorter (e.g., 9-mer and 10-mer) but still ending at the same residue (D421) in order to generate end-specific antibodies (tau 413-421 and 412-421, respectively). While New York teaches the 15-mer is successful, the state of the art was such that 5-mers appear to be preferred because this length places the amino terminus in a “critical” or “essential” position. It is not clear that peptides of any length would function to achieve not only the critical end-specific binding now claimed, but all of the other claimed properties as well. As such, the claims are deemed non-obvious.
Regarding claims limited to using TauC3, the closest prior art is New York in view of Basurto-lslas (IDS 5/10/23 citation A87). While Basurto-lslas teaches TauC3 antibodies, as well as the pathogenic relevance of E391/D421, Basurto-lslas does not teach the antibodies in a therapeutic capacity. Moreover, while New York does teach using antibodies against truncated forms of tau, New York does not teach TauC3 as a specific example of such antibodies, but rather teaches truncations and epitopes not covered by the instant claims. While one of ordinary skill would be motivated to find other epitopes, there is no teaching in Sigurdsson that would motivate one of ordinary skill to use TauC3 and no teachings in Basurto-lslas which would provide an expectation that TauC3 would be a useful therapeutic. There is no other evidence on the record that would render such combination or motivation obvious. While TauC3 is an old product, a method to a new use may be patentable. Thus, the method of using TauC3 to treat FTD in a human is patentable over the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Adam Weidner/ Primary Examiner, Art Unit 1675