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 .
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.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/EP2023/050628, filed 01/12/2023. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. 2200326.3, filed on 01/12/2023 in the United Kingdom.
Information Disclosure Statement
The information disclosure statement (IDS) filed 09/04/2024 and 12/13/2024 are considered, initialed and are attached hereto.
Status of the Claims
Claims 1-2, 6-7, 10, 12-13, 16-19, 23-24, 26 and 30-35 are pending; claims 3-5, 8-9, 11, 14-15, 17, 20-22, 25, 27-29 and 36-53 are cancelled; claims 2, 6-7, 10, 12-13, 16, 18-19, 23, 26 and 30-35 are amended. Claims 1-2, 6-7, 10, 12-13, 16-19, 23-24, 26 and 30-35 are examined below.
Drawings
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
See for example, Figures 2, 4, 6, 40 each show a sequence in the drawings, however the sequence is not accompanied with appropriate sequence identifier in either of the drawing OR the description of the drawings at pages 2-9 of the originally filed specification.
Specification
The disclosure is objected to because of the following informalities:
The specification recites at page 3, lines 2, 10, the abbreviation “1D12” as an abbreviation for antibody “S1D12” (see the alternative only first presented with S1D12 at page 30, line 4). Everywhere other than page 3 the specification refers to this antibody as “S1D12”. It is suggested that these two instances be changed to “S1D12” to improve clarity and consistency in the record.
See also the specification at page 257, second paragraph of Example 35, “SD12” appears to be a typographical error (it appears this should read as “S1D12”).
Appropriate correction is required.
Claim Objections
Claim 33 is objected to because of the following informalities:
Claim 33 refers to sequences “as set forth in table 10”. See MPEP 2173.05(s), “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”. The claim is objected to for reference to tables in the specification.
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 1-2, 6, 10, 12, 16, 18, 23, 24, 26 and 31-35 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.
Claim 1 recites “a first specific binding molecule wherein the first specific binding molecule binds to an epitope within residues 297 to 391 of SEQ ID NO. 1”. The claim encompasses a large genus of products that may be characterized by substantial variability, the genus described in terms of functional ability, namely binding (i.e., the ability to bind and detect tau protein or a fragment thereof at a location within residues 297-391 of SEQ ID NO. 1). For example, regarding the breadth of the genus, “specific binding molecule” is also not clearly limited to antibodies or even polypeptides, and as such, any compound that is like in any way falls within the scope of the claimed genus. Even in the case of specific binding molecules that are antibodies, the claims encompass a large and highly variable genus as there are no minimum or maximum number of substitutions or other types of alterations, any size would meet the structural requirements of the claim.
Additionally, with respect to claim 1, the claim fails to recite any specific structural features specific to the binding molecule itself.
The claim scope is potentially enormous depending on how many of the products that meet the structural requirements would also meet the functional requirements (binding an epitope the same region as claimed, see notably the claim specifies that the epitope is within the indicated region, not that this region itself is the epitope); by contrast, the scope of the description which only includes specific species of antibodies that achieve binding as claimed, is extremely narrow.
Claim 2 does further specify narrower regions containing the epitope to which the “specific binding molecule” binds, however these limitations fail to further indicate any identifying structural features/characteristics specific to the first specific binding molecule itself.
Claim 6 does provide additional structural identity, see specifically the claim limitations indicating the binding molecule is an antibody (described in terms of its 6 CDRs), however, the claim recites “comprises the CDRs VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2 and VLCDR3, wherein each of said CDRs comprises an amino acid sequence as follows” the claim reciting each of SEQ ID Nos. 16, 18, 21, 24, 26 and 29, respectively, “or for each CDR sequence, an amino acid sequence with (i) at least 85% identity thereto, and/or (ii) one, two or three amino acid substitutions relative thereto”. However, the claimed language fails to indicate which residues necessarily must be retained in order to retain the desired functional ability, i.e., it is not clear which positions for each CDR can tolerate, for example, addition, deletion or substitution (regarding the indicated 85% identity), or a substitution (referring to claimed (ii)).
The originally filed specification does specify certain variations that can be tolerated for given residues (see referring, for example to the specification, page 28), or the sequence listing). For example, VHCDR1 (SEQ ID NO. 16 as claimed) appears to be shared among the different antibodies S1D12 and S2C1, and can tolerate a substitution from N to S as residue 1 (SEQ ID NO. 17), however, the CDR is combined with different specific CDRs (for example, based on the information at the sequence listing, this CDR (SEQ ID NO. 17), is present in antibodies ME12, NS3D9, S1D2, S1H6, S2C3, etc.). Every antibody has its own combination of 6 specific CDRs.
The combination of SEQ ID Nos. 16, 18, 21, 24, 26 and 29 (claims 6 and 7) are specific to antibody S1D12 of the originally filed specification.
Claims 12, 18, 31, 32, and 33 are similarly to claim 6 discussed above, in that each claim limits to an antibody (see referring to 6 CDRs required for binding), each of these claims also encompass antibodies comprising CDRs having at least 85% identity to the sequences recited.
See for example, claim 12 recites SEQ ID Nos. 42, 46, 54, 63, 70, 73, the recited language encompasses the species of antibody that is S1G2, but is not limited to only this species of antibody, the language similarly does not specify which residues can tolerate variation and which must be retained.
Claim 18 recites CDR SEQ ID Nos. 83, 84, 89, 91, 95, 97, the recited language encompasses the species of antibody that is NS2A3, but is not limited to only this species of antibody, the language similarly does not specify which residues can tolerate variation and which must be retained.
Claim 31 recites CDR SEQ ID Nos. 198, 200, 202, 204, 206 and 208, the only antibody species disclosed which shares all 6 of these CDRs required for binding is 3aD6. Similarly, as above with the other species, while this CDR may be shared among more than 1 antibody (as is supported by Applicant’s originally filed specification/Sequence listing), one cannot readily predict from one CDR what the other required CDRs would be (in terms of structure required to retain binding).
Claim 32 recites CDR SEQ ID Nos. 17, 201, 203, 138, 207, 209, which each of the specific sequences (without variation) are specific to antibody 3aA6.
Claim 33 recites the CDRs as “set forth in table 10”, the language further reciting “(i) or for each CDR sequence, an amino acid sequence with (i) at least 85% identity thereto, and/or (ii) one, two, or three amino acid substitutions relative thereto”. However, referring to table 10, the table discloses specific clone names which each have their own specific combination of the CDR sequences. The CDR sequences are not, for example, interchangeable (i.e., one could not readily predict that any combination of any CDR sequences in Table 10 together would achieve binding and detection as claimed, considering 6 CDRs together are typically required to describe a given paratope, see discussed in further detail below).
While Applicant’s specification (for example, referring to Table 10, and to the sequence listing) indicates specific examples of antibodies that meet both the structural and functional requirements of the claim, these disclosed examples are much narrower in scope than Applicant’s claims.
Although with the aid of a computer it may be possible to determine the amino acid sequences of the proteins that meet the structural requirements of the claims, it is not readily apparent from the claims or the specification, which of those sequences retains the claimed binding ability and binds/detects Tau protein within the desired region of SEQ ID NO. 1.
The claim language “at least 85%” identity, for example, may appear somewhat limiting, however is actually potentially large and variable in scope because it encompasses several possible substitutions, deletions or additions at any of the positions.
Applicant does not appear to be in possession of any and all additional species encompassed by the recited structural and functional language, other than those specifically disclosed. It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).
However, the record here does not indicate such an established correlation. The claims attempt to claim every specific binding molecule that would achieve a desired result, i.e. of binding an epitope(s) within the disclosed region of SEQ ID NO. 1. Even among the disclosed CDRs, there is substantial variation between different antibodies that share a given CDR in that the other CDRs are structurally very distinct.
As discussed above, claim 1 is extremely broad and does not provide any structure specific to the “binding molecule” itself (is not even limited to an antibody, as noted above).
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding, binding to a certain epitope), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
Along these same lines, a more recent Federal Circuit decision, Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; not just a description of the sequence to which the antibody binds. Amgen, 872 F.3d at 1378-79.
It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date” (AbbVie, 759 F.3d at 1298, reiterating Enzo Biochem, Inc., 323 F.3d at 964)(emphasis added).
In the present case, however, there is insufficient evidence of such an established structure-function correlation in the case of binding molecules, or even antibodies, that bind to the same region as claimed (epitope in the claimed region of SEQ ID NO. 1).
As discussed in the recent case of Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), see page 17:
An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5–16) (Appellants’ expert Dr. Eck testifying that knowing “that an antibody binds to a particular amino acid on PCSK9 . . . does not tell you anything at all about the structure of the antibody”); J.A. 1314 (836:9–11) (Appellees’ expert Dr. Petsko being informed of Dr. Eck’s testimony and responding that “[m]y opinion is that [he’s] right”); Centocor, 636 F.3d at 1352 (analogizing the antibody- antigen relationship as searching for a key “on a ring with a million keys on it”) (internal citations and quotation marks omitted).
Amgen Inc. v. Sanofi further notes, pointing to Ariad Pharms., Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed Cir. 2010):
To show invention, a patentee must convey in its disclosure that it “had possession of the claimed subject matter as of the filing date.” Id. at 1350. Demonstrating possession “requires a precise definition” of the invention. Id. To provide this “precise definition” for a claim to a genus, a patentee must disclose “a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id.
Amgen at pages 7-8.
However, even in this case, there is substantial variability among different antibodies in terms of their 6 CDRs. There is substantial variability specific to teach genus (referring to claims 1 and 33 (table 10 CDRs), but even further to each genus as encompassed by each of claims 12, 18, 31, 32, and 33. Since there are a substantial variety of compounds possible within each genus, without disclosure of any common partial structure or other sufficient identifying characteristics of the genus, the examples do not constitute a representative number of species and do not sufficiently describe the genus claimed.
It is not within the skill level of one of ordinary skill in the art to predict any and all variations from any specific combination of the 6 claimed CDRs that would result in products that retain the binding properties of a parent antibody. The art recognizes that structure is not necessarily a reliable indicator of function.
The teachings of Harlow et al. (Antibodies, A Laboratory Manual, Cold Spring Harbor laboratory, 1988, pages 25-26 and 37-59) which describe how the steps of the humoral immune response to an immunogen are dependent on APC, T-cell and B-cell recognition and processing of the immunogen in ways well known in the art to be highly unpredictable and heavily influenced by the particular immunogen and the specifics of the immunization protocol. Harlow et al. teach that even small changes in structure, such as loss of a single hydrogen bond, can profoundly affect antibody-antigen interaction (p. 25, last paragraph to page 26, second paragraph).
The principles laid out in Harlow are further illustrated in the teachings of Edwards et al. ("The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS" J. Mol. Biol. (2003) 334, 103–118, DOI: 10.1016/j.jmb.2003.09.054), which shows the immense combinatorial flexibility and capacity of the human antibody repertoire to generate binding sites to an individual protein antigen, the B-lymphocyte growth factor known as “BLyS” (see entire document). Edwards describes in detail how the breadth of antibody structures against a given immunogen can be influenced by the immunization and/or selection methods (see Discussion Section).
See also, it is well established in the prior art (see Rudikoff et al., Single amino acid substitution altering antigen binding specificity, Proc. Natl. Acad. Sci. USA, 79, (1982), p. 1979-1983) 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. Rudikoff supports that it is necessary to have the full length sequence of each of the heavy and light chain sequences of the antibody because see Rudikoff teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
The prior art also recognized that the full six CDRs are required to form the part of the antibody that specifically binds the target antigen. Al Qaraghuli et al. ("Antibody-protein binding and conformational changes: identifying allosteric signaling pathways to engineer a better effector response," Nature Scientific Reports (2020)10(1):13696, https://doi.org/10.1038/s41598-020-70680-0), discuss how the six CDRs together form a continuous surface to form the 'paratope' or antigen-binding region that binds the epitope of the cognate antigen (page 2).
As yet another example to illustrate the potential scope of the genus of antibodies encompassed by the instant claims, consider the teachings of Meyer et al. (“New Insights in Type I and II CD20 Antibody Mechanisms-Of-Action With a Panel of Novel CD20 Antibodies”, British Journal of Haematology, 2018, 180, 808–820, |https://doi.org/10.1111/bjh.15132). Meyer describes the core binding region of the well-known anti-CD20 antibody rituximab corresponds to amino acid residues 170ANPS173, wherein N171 is the key residue for binding. By contrast, the OBZ and B1 anti-CD20 antibodies share an overlapping epitope with rituximab (170ANPSEKNSP178); however, in contrast to rituximab residues at positions 176–178 contribute the most to binding (see page 809, left col., 2nd full paragraph).
Meyer also described the production and characterization of a panel of new anti-CD20 antibodies which were shown to bind epitopes contained within or nearby the rituximab 170ANPS173 epitope but to bind to different residues than rituximab binds in this region (see page 811, “New CD20 mAbs with overlapping, but distinct epitopes,” see also page 815-16 bridging paragraph).
More particularly, Meyer teaches the newly created anti-CD20 mAbs m1 and m2 were found to bind within but also in the vicinity of the rituximab binding site (m1 and m2) and elsewhere (m2):
“detailed epitope mapping was performed for both mIgG2c-CD20 mAbs m1 and m2, by using PepScan technology. We identified the critical residues of m1 to be 168EPANPSEK175 by using linear (Figure S2A) and circular (Fig 2C, left) peptides with a positional amino acid scan covering the larger extracellular loop. Also for m2, a signal decrease below the WT binding signal occurred within the 168EPANPSEK175 sequence motif but the binding signal to the linear (Figure S2B) and circular (Fig 2C, right) peptide was rather low. This suggests that the epitope of both mAbs is located on the larger loop in the same region, however their binding characteristics are different. The data suggests that m1 binds a linear epitope, whereas m2 binds to a conformational epitope.” (see ibid).
While these antibodies bind within or nearby the rituximab 170ANPS173 epitope they do so with heavy and light chain CDRs non-homologous to those of rituximab.
As such, Meyer supports that even if multiple antibodies bind epitopes within the same small region of a given polypeptide it is not uncommon for said antibodies to bind to different amino acids even within said small region and for said antibodies to have structurally dissimilar CDRs.
Aside from the specific species disclosed (the specifically identified clones in the specification), it is not possible to visualize or recognize the identities of the members of each genus that exhibit the claimed functional properties. Making changes to antigen and/or antibody structures while preserving binding function is unpredictable, one cannot envision the structures of any other antibodies falling within the claimed genus of antibodies.
The specification fails to provide adequate written description for each genus of antibodies claimed, as with respect to claim 1, the antibodies are described only in terms of desired functional properties, and although dependent claims indicate some structure, aside from the specifically disclosed combination of 6 CDRs which specifies a particular antibody species, there is insufficient common structure or other relevant identifying characteristics to define each genus. The specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
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 24, 26, 30, and 35 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 24 recites the broad recitation “151 to 243 of SEQ ID NO. 1”, and the claim also recites “194 to 198” and “159 to 163 of SEQ ID NO. 1”, each of which is the narrower statement of the range/limitation.
Claim 35 also recites the broad recitation “is an immunoglobulin”, and the claim also recites “an immunoglobulin Fab region, a Fab’, a Fv, a Fv-Fc…” etc., reciting narrower species of immunoglobulin.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. See specifically claim 16 depends from a canceled claim, and as such fails to further limit the subject matter of the previous claim. In the interest of compact prosecution, the claim is considered to depend from a previous pending claim prior to 14 (e.g., 1 or 13). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 2, 6-7, 10, 12, 13, 16, 18, 23, 26 and 30-35 is rejected under 35 U.S.C. 103 as being unpatentable over Harrington et al., US PG Pub No. 2023/0257452A1 (effectively filed before the effective filing date of the claimed invention, ‘452 and the instant application differ by inventive entity (see the list of inventors)) in view of Shi et al., Salivary tau species are potential biomarkers of Alzheimer disease, J. Alzheimer Dis., 27(2), (2011), p. 299-305 (IDS entered 09/04/2024).
Harrington et al. similarly teach an in vitro method for detecting tau protein by contacting sample with specific binding molecule, the binding molecule the same as that recited at claims 1, 2, 6-7 and 10, e.g., antibody S1D12 is the antibody having those CDR sequences as in the instant application at claim 6 (paras [0017], [0022], [0138], [2565], [2641] and the claims).
However, Harrington et al. teach detection methods detecting in sample comprising plasma, as such fails to teach contacting a saliva sample (claim 1).
Shi et al. teach salivary tau as a potential biomarker for Alzheimer’s disease (see title and abstract). See Shi further teach saliva as a body fluid sample that is easily accessible and collected in a less invasive manner compared to CSF or even blood (page 2, para 3). See further Shi report tau as a detectable biomarker in saliva (page 2, para 3), pages 4-5 Discussion.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified Harrington to have applied the method for detection in saliva (rather than plasma as in Harrington), as an obvious matter to try, one motivated as a result of Shi et al., specifically because Shi teach saliva as a sample having detectable Tau and further because Shi teach saliva is considered an easily accessible with non-invasive collection (as compared to blood samples). One having ordinary skill in the art would have a reasonable expectation of success because Shi specifically suggest salivary Tau as a potential marker for Alzheimer’s, so the modification would essentially simply sample collection for the method of Harrington.
Regarding claim 12, see as noted previously above, the CDRs of instant claim 12 correspond to antibody S1G2, Harrington further teach specific binding molecule that is antibody S1G2 (see paras [0276], [0287]). As such, Harrington et al. further addresses claims 12, 13 and 16).
Regarding claim 18, see as noted previously above, the CDRs of instant claim 18 correspond to antibody NS2A3, Harrington further teach specific binding molecule that is this antibody as well (see paras [0497] and [0508]). As such, Harrinton et al. further addresses claims 18 and 19.
Regarding claims 23, 26 and 30, Harrington teach further contacting with a second specific binding molecule, BT2 or HT7 (para [2596]-[2597]).
Regarding claim 31, see Harrington at paras [1027]-[1038], addressing antibody binding molecule having the claimed CDRs as at instant claim 31.
Regarding claim 32, see Harrington at para [1027], addressing antibody binding molecule having the claimed CDRs as at instant claim 32.
Regarding claim 33, see Harrington et al. at para [2214] and Table 10.
Regarding claim 34, Harrington et al. also teach the same (see as cited, para [2214], and e.g., para [02171] CC5 as an example, and Table 10).
Regarding claim 35, see for example paras [2401] (e.g., diabody).
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.
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Claims 1, 2, 6, 7 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,624,096 B2 in view of Shi et al., Salivary tau species are potential biomarkers of Alzheimer disease, J. Alzheimer Dis., 27(2), (2011), p. 299-305.
Claim 1 of Harrington et al. is VH and VL sequences comprising the CDRs as claimed (specific to antibody S1D12, referring to the sequence listing for Harrington et al.), see claim 14 of Harrington and in vitro method of detection as claimed.
However, Harrington et al. teach detection methods detecting in sample comprising plasma, as such fails to teach contacting a saliva sample (claim 1).
Shi et al. teach salivary tau as a potential biomarker for Alzheimer’s disease (see title and abstract). See Shi further teach saliva as a body fluid sample that is easily accessible and collected in a less invasive manner compared to CSF or even blood (page 2, para 3). See further Shi report tau as a detectable biomarker in saliva (page 2, para 3), pages 4-5 Discussion.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified Harrington to have applied the method for detection in saliva (rather than plasma as in Harrington), as an obvious matter to try, one motivated as a result of Shi et al., specifically because Shi teach saliva as a sample having detectable Tau and further because Shi teach saliva is considered an easily accessible with non-invasive collection (as compared to blood samples). One having ordinary skill in the art would have a reasonable expectation of success because Shi specifically suggest salivary Tau as a potential marker for Alzheimer’s, so the modification would essentially simply sample collection for the method of Harrington.
As such, Harrington et al. in view of Shi et al. addresses claims 1, 2, 6, 7, 10 as claimed presently.
Claims 23-24, 26 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,624,096B2 in view of Shi et al., as applied to claim 1 above, and further in view of Vasan et al., US PG Pub No. 2008/0220449A1.
Regarding claims 23-24, 26 and 30, see Harrington teaches a method substantially as claimed, however, fails to teach further contacting with a second specific binding molecule that binds as recited at claim 24, and claim 26 (BT2 or HT7).
See Vasan et al., mAb HT7 is a known antibody for detecting Tau (binding and detection Tau captured/detected using a first specific antibody, see HT7 recognized as an antibody for binding total tau, paras [0082], [0096]).
It would have been prima facie obvious to one having ordinary skill in the art to have modified Harrington et al., to further contact the specific binding partner/tau complex with a second antibody (specific binding molecule) for tau, such as HT7, as an obvious matter of applying a known technique and reagent to a known method. In particular, see Vasan et al., it was known in the art to use two antibody binding assay (such as ELISA) for detection of Tau (this is an art recognized technique for detecting Tau bound first capture antibody. Additionally, HT7 is an art recognized, available antibody known in the art for binding recognizing Tau. One having ordinary skill in the art would have a reasonable expectation of success using known binding assay technique and reagents for the detection of Tau.
Regarding claim 35, Harrington teach specific binding molecule that is an immunoglobulin.
Correspondence
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/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677
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