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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/12/2026 has been entered.
Withdrawn Rejections
The rejections under 112b are withdrawn in response to the amendments. However, new grounds of rejection are set forth below.
The rejection of claim 10 and its dependents under 103 are withdrawn in response to the amendments. However, new grounds of rejection are set forth below.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2020/037603, filed 6/12/2020, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/861,003, filed 06/13/2019.
Status of the Claims
Claims 1, 3-10 and 12-22 are pending; claims 1, 10 and 18-19 are amended, claims 2 and 11 are canceled; claims 4, 13 and 19-22 are withdrawn. Claims 1, 3, 5-10, 12 and 14-18 are examined below.
New Objections
Claim Objections
Claims 6, 10 and 15 are objected to because of the following informalities:
In claims 6 and 15, “is a sera sample” appears to be a typographical error, namely it is suggested that “is a sera sample” read as “is a serum sample”.
In claim 10, last line, “detecting binding” appears to be a typographical error, namely it is suggested that “detecting binding” read as “and detecting binding” (emphasis added) as per claim 1.
Appropriate correction is required.
Maintained Rejections
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, 3, 5-10, 12 and 14-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims recite “one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TAR DNA-binding protein 43 (TDP-43) TDP-43 variants and/or tau variants, wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 and wherein the light chain complementary determining region (CDR) and heavy chain CDR of the one or more scFvs have 100% sequence identity to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114” (claim 1) or “wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of: SEQ ID NOS: 21, 24, 41, 61, 64, and 83; SEQ ID NOS: 21, 24, 41, 101, and 103; SEQ ID NOS: 21, 25, 42, 61, 65, and 84; SEQ ID NOS: 21, 26, 43, 62, 66, and 85; SEQ ID NOS: 21, 26, 43, 101, and 104; SEQ ID NOS: 21, 27, 44, 61, 67, and 86; SEQ ID NOS: 21, 27, 44, 101, and 105; SEQ ID NOS: 21, 28, 45, 61, 68, and 87; SEQ ID NOS: 21, 28, 45, 101, and 106; SEQ ID NOS: 22, 29, 46, 61, 69, and 88; SEQ ID NOS: 22, 29, 46, 101, and 107; SEQ ID NOS: 23, 30, 47, 63, 70, and 89; SEQ ID NOS: 23, 30, 47, 102, and 108; SEQ ID NOS: 21, 31, 48, 61, 71, and 90; SEQ ID NOS: 21, 31, 48, 101, and 109; SEQ ID NOS: 21, 32, and 49; SEQ ID NOS: 21, 27, 50, 61, 72, and 91; SEQ ID NOS: 21, 26, 51, 61, 73, and 92; SEQ ID NOS: 21, 26, 51, 101, and 110; SEQ ID NOS: 21, 33, 52, 61, and 74; SEQ ID NOS: 21, 33, 52, 101, and 111; SEQ ID NOS: 21, 34, 53, 61, 75, and 93; SEQ ID NOS: 21, 34, 53, 101, and 112; SEQ ID NOS: 21, 35, 54, 61, 76, and 94; SEQ ID NOS: 21, 35, 54, 101, and 113; SEQ ID NOS: 21, 36, 55, 61, 77, and 95; and SEQ ID NOS: 21, 36, 55, 101, and 114” (claim 10).
However, the specification does not describe which amino acid residues are present in the genus of scFvs encompasses by the claims. Furthermore, the specification fails to disclose the structures common to all members of the genus and fails to provide sufficient specific examples of agents to be used. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described. Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement.
Regarding the claimed scope that includes antibodies, the Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While the specification discloses in Table 3 (pages 18-20) examples of amino acid sequence modifications to specific CDR regions of 15 scFvs, i.e. the claimed SEQ ID NOS: 1-15, these are not sufficient to encompass the claimed scope of scFvs at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants, wherein the scFvs have at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15. The structure of the presently recited antibodies can vary substantially within the above given claimed recitations. Although claim 1 limits the CDR of the one or more scFvs to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114, the claimed scope still encompasses a wide range of possible antibodies which are not properly disclosed. Note that an antibody contains 6 CDRs, “Light chain CDRs are sometimes referred to as LCDRl, LCDR2, and LCDR3. Heavy chain CDRs are sometimes referred to as HCDRl, HCDR2, and HCDR3” (specification para. 53). Therefore, given that claim 1 does not clearly limit the one or more scFvs to the respective 6 CDR sequences (LCDRl, LCDR2, LCDR3, HCDRl, HCDR2, and HCDR3), a person having ordinary skill in the art would question the possession of the genus of scFvs at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants claimed. Similarly, claim 10 limits the CDR of the scFv to comprise at least one combination. However, the claim does not limit each scFv to its corresponding CDRs as disclosed in Table 3. Therefore, the claim encompasses combinations of scFvs that are not properly disclosed, which raises concerns under 112a written description. A person having ordinary skill in the art would question whether Applicant was in possession of the genus of antibodies encompassed by the claim. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of scFvs at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants, wherein the scFvs have at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 of the claims.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “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." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the full genus of antibodies encompassed by the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of encompassed antibodies.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
New Rejections
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 5-10, 12 and 14-18 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.
The claims recite “one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TAR DNA-binding protein 43 (TDP-43) variants and/or tau variants, wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15”. Claim 1 limits the CDR of the one or more scFvs to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114. Claim 10 limits the CDR of the scFv to comprise at least one combination (see claim 10).
However, Table 3 of the specification discloses specific antigen targets to SEQ ID NOS: 1-15, as well as specific set of CDRs corresponding to each scFv. Therefore it is not clear how the claimed scFvs would be reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants. For example, the specification paragraph 69 and Table 3 discloses that SEQ ID NOS: 1-2 and 5 target “a-syn”, which is not a beta amyloid variant, a TDP-43 variant and/or a tau variant. The rest of the scFvs disclosed appear to target a single antigen, i.e. beta amyloid, TDP-43 or tau; not beta amyloid, TDP-43 and/or tau. Indeed, the specification suggests that CDRs limit the scFv to a single target antigen, not a possible combination of three different antigens and variants thereof as claimed (“The CDRs are primarily responsible for binding to an epitope of an antigen” para. 53). The specification further discloses that “ [s]even scFvs that are reactive with variants ofTDP-43 including AD-TDPl, AD-TDP2, AD-TDP3, ALSTDPl0, ALS-TDP14, SFTD-TDPl and SFTD-TDP2, three scFvs that are reactive with oligomeric variants of beta-amyloid including A4, El and C6T, two scFvs that are reactive with oligomeric variants of tau including F9T and D11C and two scFvs that are reactive with oligomeric variants of alpha-synuclein including 10H and D5 were included in the panel” (para. 151), which further suggests that the scFvs claimed target a single antigen not the group of beta amyloid, TDP-43 and/or tau claimed. Because of this, a person having ordinary skill in the art would not recognize the metes and bounds of the claim.
Furthermore, the term “variant” is unclear throughout the claims. The specification discloses a broad definition of variants, i.e. “[v]ariants: sequences derived by deletion (so-called truncation) or addition of one or more amino acids to the N-terminal and/or C-terminal end, …; deletion or addition of one or more amino acids/nucleic acids at one or more sites in the sequence; or substitution of one or more amino acids/nucleic acids at one or more sites in the sequence” (para. 66). This extensive definition of variants encompasses such a broad scope that a person having ordinary skill in the art would not be able to recognize the metes and bounds of the claimed invention.
The claims further recite “diagnosing a subject…detecting binding between the one or more scFvs and the biological sample” (claim 1), “the detection of binding between the one or more scFvs to the biological sample is indicative that the subject has or is likely to develop FTD” (claim 2), “monitoring a subject…detecting binding between the one or more scFvs and the first biological sample” (claim 10), “detecting binding between the one or more scFvs and the second biological sample” (claim 18). However, it is not clear how detecting binding between the one or more scFvs and the biological sample would relate to FTD. Notably detecting binding between the one or more scFvs and the biological sample is not the same as detecting binding between the one or more scFvs and the one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants. Because of this, a person having ordinary skill in the art would question the metes and bounds of the claim.
Furthermore, claims 3 and 12 recite, “wherein the one or more scFvs is reactive with one or more oligomeric beta amyloid variants”. However, as explained above, the specification discloses specific target antigens to the claimed scFvs. For example, SEQ ID NOS: : 1-2 and 5 target “a-syn”. Therefore, it is not clear how the scFvs claimed are reactive with one or more oligomeric beta amyloid variants.
Claim 10 recites the limitation "the scFv" in line 9. There is insufficient antecedent basis for this limitation in the claim. Although the claim recites “one or more scFvs” in lines 3-5, the language “the scFv” used in line 9 raises doubt as to which of the one or more scFvs is being referred. Because of this, a person having ordinary skill in the art would question the metes and bounds of the claim. Furthermore, claim 10 recites “at least one combination” of CDRs, which is unclear because an scFv only has 6 CDRs. How can the scFv comprise more (or less) than one combination of 6? Also, in line 25, the combination “SEQ ID NOS: 21, 32, and 49” is unclear because the combination only recites 3 CDRs. Given that the claim is to both light chain and heavy chain CDRs, and the specification suggests that 6 CDRs are needed to detect the target (para. 53), it is not clear how 3 SEQ ID NOS make up both light chain and heavy chain CDRs.
For these reasons the claims are indefinite.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3, 5-10, 12 and 14-18 are rejected under 35 U.S.C. 101 because the claims are directed to a natural correlation without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Prong One asks does the claim recite an abstract idea, law of nature, or natural phenomenon? In Prong One examiners evaluate whether the claim recites a judicial exception, i.e. whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words "intermediated" or "settlement." See MPEP 2106.04 (II)(A)(1).
Claims 1 and 10 recite “a method of diagnosing a subject with frontotemporal dementia (FTD)” (claim 1) or “a method of monitoring a subject with frontotemporal dementia (FTD)” (claim 10), “contacting a biological sample from a subject at risk or suspected of having FTD” (claim 1) or “contacting a first biological sample from a subject diagnosed with FTD” (claim 10) “with one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants…and detecting binding between one or more scFvs and the…sample”.
The natural relationship to which the claims are directed (i.e., the relation between oligomeric beta amyloid variants, TDP-43 variants and/or tau variants and frontotemporal dementia as measured by detecting binding between the sample, and in extension said biomarkers, and scFvs) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring presence of one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants and FTD.
The correlation between oligomeric beta amyloid variants, TDP-43 variants and/or tau variants and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that levels of oligomeric beta amyloid variants, TDP-43 variants and/or tau variants are elevated to different extents in FTD vs. in disorders not affecting the nervous system.
Claims 3 and 12 further limit the biomarker to “one or more oligomeric beta amyloid variants” to which the natural correlation is directed to. Claim 3 further limits the natural correlation to be “indicative that the subject has or is likely to develop FTD”.
Claims 5-7 and 14-15 further limit the sample or individual to which the natural correlation is directed to.
Claim 18 recites “contacting the second biological sample with one or more scFvs at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants… and detecting binding between one or more scFvs and the second biological sample”. Claim 18 further limits the natural correlation to a “second biological sample from the subject”.
Step 2A, Prong 2
Regarding claims 1, 10 and 18, see the claim further recite the limitations of “wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15”, “and wherein the light chain complementary determining region (CDR) and heavy chain CDR of the one or more scFvs have 100% sequence identity to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114” (claims 1 and 18) or “wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of: SEQ ID NOS: 21, 24, 41, 61, 64, and 83; SEQ ID NOS: 21, 24, 41, 101, and 103; SEQ ID NOS: 21, 25, 42, 61, 65, and 84; SEQ ID NOS: 21, 26, 43, 62, 66, and 85; SEQ ID NOS: 21, 26, 43, 101, and 104; SEQ ID NOS: 21, 27, 44, 61, 67, and 86; SEQ ID NOS: 21, 27, 44, 101, and 105; SEQ ID NOS: 21, 28, 45, 61, 68, and 87; SEQ ID NOS: 21, 28, 45, 101, and 106; SEQ ID NOS: 22, 29, 46, 61, 69, and 88; SEQ ID NOS: 22, 29, 46, 101, and 107; SEQ ID NOS: 23, 30, 47, 63, 70, and 89; SEQ ID NOS: 23, 30, 47, 102, and 108; SEQ ID NOS: 21, 31, 48, 61, 71, and 90; SEQ ID NOS: 21, 31, 48, 101, and 109; SEQ ID NOS: 21, 32, and 49; SEQ ID NOS: 21, 27, 50, 61, 72, and 91; SEQ ID NOS: 21, 26, 51, 61, 73, and 92; SEQ ID NOS: 21, 26, 51, 101, and 110; SEQ ID NOS: 21, 33, 52, 61, and 74; SEQ ID NOS: 21, 33, 52, 101, and 111; SEQ ID NOS: 21, 34, 53, 61, 75, and 93; SEQ ID NOS: 21, 34, 53, 101, and 112; SEQ ID NOS: 21, 35, 54, 61, 76, and 94; SEQ ID NOS: 21, 35, 54, 101, and 113; SEQ ID NOS: 21, 36, 55, 61, 77, and 95; and SEQ ID NOS: 21, 36, 55, 101, and 114” (claim 10). However, this limitation fails to further amount to a practical application of the indicated judicial exception(s). Specifically, these steps does not particularly or directly apply, rely on or use the natural correlation such that it imposes a meaningful limit on the judicial exception. This limitation merely limits the scFvs used in the natural correlation.
Claims 8 and 17 further limit the detecting step, however, this limitation also fails to practically apply the judicial exception. Claims 8 and 17 recite “wherein the method is performed utilizing an enzyme linked immunosorbent assay (ELISA)”, however no particular active, wet method steps are recited/performed.
Similarly the limitations recited at claims 9 and 18, i.e., “administering a treatment to the subject diagnosed with FTD” (claims 9 and 18) “to treat one or more symptoms associated with FTD” (claim 9), fail to practically apply the indicated judicial exceptions. These steps are insufficient to integrate the judicial exception as they are not limited to a particular treatment.
The recited steps of “administering a treatment to the subject diagnosed with FTD” are recited at a high level of generality and are not limited to a particular treatment. Such highly generalized treatment limitations – which do not require any specific treatment for FTD/symptoms of FTD – do not amount to sufficient practical application to provide patentability. Although a claim limitation can integrate a judicial exception by applying or using the judicial exception(s) to effect a particular treatment or prophylaxis for a disease or medical condition, in this case no specific or particular treatment is set forth.
The level of generality in the instant claims stands in contrast to the treatment claims found patent-eligible in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018) and Natural Alternatives Int’l v. Creative Compounds LLC, 2017 WL 1216226 (Fed. Cir. Mar. 15, 2019). The claims at issue in Vanda recited administering a specific drug (iloperidone) at specific dosage ranges based on a patient’s genotype. Vanda, 887 F.3d at 1135. Accordingly, the court found that although the inventors recognized the relationships between iloperidone, a patient’s genotype, and QTc prolongation, what they claimed is “an application of that relationship,” i.e., “‘a new way of using an existing drug’ that is safer for patients because it reduces the risk of QTc prolongation.” Id. (quoting Mayo, 566 U.S. at 87). The Federal Circuit characterized the Vanda claims as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” Id. at 1136. Similarly, the Federal Circuit found that the claims in Natural Alternatives “contain specific elements that clearly establish they are doing more than simply reciting a natural law,” such as specifying a patient population, particular results to be obtained, specific compounds to be administered to achieve the claimed results, and dosages via an “effective” limitation. Natural Alternatives, 4-5.
In contrast to the claims in Vanda and Natural Alternatives, the present claims do not specify a compound to be administered to achieve a claimed result, or any specific dosage of a specific compound.
The recited treating steps do not limit the claims to a particular application; instead, the effect of the treatment limitations “is simply to tell doctors to apply the law somehow when treating their patients.” Mayo, 566 U.S. at 81-82. Thus, the treatment step does not integrate the judicial exception into a practical application.
Claims 7, 16 and 18 recite the additional limitation “obtaining the biological sample from the subject” (claim 7), or “obtaining the first biological sample from the subject diagnosed with FTD” (claim 16) or “obtaining a second biological sample from the subject” (claim 18). The “obtaining” does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015).
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exception; the additional recited claim elements are recited at a high level of generality, and are not, for example limited to any particular testing technique of or platform, or treatment as claimed.
Sierks et al. (WO 2015117088)-Cite No. 3 of IDS filed 1/12/2024 (“Williams”) disclose a “method of treating FTD…in the brain of a mammal comprising administering to the mammal a composition comprising an antibody fragment or a binding molecule described above” (page 5 lines 1-3). Furthermore, Williams discloses that “[t]he scFv compositions of the invention can be used in any diagnostic assay format to determine the presence of TDP-43 associated with ALS or FTD. A variety of immunodetection methods are contemplated for this embodiment. Such immunodetection methods include enzyme linked immunosorbent assay (ELISA)” (page 15 lines 23-26).
Furthermore, the specification paragraph 91 discloses that “[c]ertain preferred immunoassays are the various types of enzyme linked immunosorbent assays (ELISAs) and/or radioimmunoassays (RIA) known in the art”.
Also the specification paragraph 103 discloses that “[a]s noted above, there are various drugs that are presently in use or under development for the treatment of FTD”.
Furthermore, the limitation “wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15, wherein the light chain complementary determining region (CDR) and heavy chain CDR of the one or more scFvs have 100% sequence identity to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114” is well-understood routine and conventional.
For example, Sierks et al. (US 20190010504 A1) ("Sierks"). Sierks suggests a method of diagnosing a subject with frontotemporal dementia (FTD) (“increasing evidence also implicates oligomeric forms of tau as having a direct role in disease pathogenesis of AD and other tauopathies such as Frontotemporal Dementia (FTD)” paragraph 3, “these reagents can be used to detect the presence of biomarkers which can readily detect and distinguish many related neurodegenerative diseases including…FTD” paragraph 55) the method comprising: contacting a biological sample from a subject at risk or suspected of having FTD, wherein the subject is believed to be at risk or afflicted with FTD, with one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants, (“one exemplary ELISA, ligands (e.g., scFvs) are immobilized … Then, a test composition suspected of containing a target oligomer, such as a clinical sample (e.g., a biological sample obtained from the subject), is added to the wells” paragraph 123, “the reagents presently developed have well defined specificities and selectivities for selected tau forms and facilitate specific diagnoses of AD and other tauopathies. In combination with other protein and morphology specific reagents against Aβ and a-syn species” paragraph 55), wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 (“antibody fragments described herein…SEQ ID NO: 38” paragraph 15, see sequence in page 18). Note that SEQ ID NO: 38 is 93.4% matched to SEQ ID NO: 8 (Applicant’s elected species). Note that SEQ ID NO: 38 of Sierks comprises SEQ ID NOS: 21, 61 and 101 with 100% match.
Furthermore, Golde et al. (US 20100143365 A1) (“Golde”) teaches “methods and materials related to anti-amyloid antibodies” (Abstract). Golde teaches “amino acid (SEQ ID NO:6) sequences of an anti-amyloid scFv designated Pan SUP73” (paragraph 19). Note that SEQ ID NO: 6 of Golde is 91.7% matched to SEQ ID NO: 8. Note that SEQ ID NO: 6 of Golde comprises SEQ ID NOS: 21, 61 and 101 with 100% match. Note that Golde teaches that “this document features a substantially pure antibody having binding affinity for an Aβ epitope, wherein the Aβ epitope is the epitope of scFv Pan…SUP73” (paragraph 11), which reads on the claim. Therefore, Golde also shows further evidence that the limitation “wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15” is well-understood routine and conventional.
Also, it appears that the limitation “wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of:…” in claim 10 is well-understood, routine and conventional.
For example, the specification discloses that “In one particular example, a quantitative ELISA is constructed for detection of at least one of the FTD protein antigens disclosed herein, such as those listed in Table 3. These immunoassays utilize antibodies, such as mAbs commercially available” (para. 112), which suggests that the sequence combinations of Table 3 are well-understood, routine and conventional.
Furthermore, Sierks and Williams (US 20160320412 A1)-Cite No. 1 of IDS 1/12/2024 (“Williams”) teaches scFvs for distinguishing neurodegenerative diseases (Abstract and para. 88). Williams further teaches that “the capture agent is scFv-A4 (Zameer, A., et al…)… scFv-l0H (Emadi, S.,et al….)… or scFv-El (Kasturirangan, S., et al….)” (para. 88), wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of: SEQ ID NOS: 21, 24, 41, 61, 64, and 83; SEQ ID NOS: 21, 24, 41, 101, and 103; SEQ ID NOS: 21, 25, 42, 61, 65, and 84; SEQ ID NOS: 21, 26, 43, 62, 66, and 85; SEQ ID NOS: 21, 26, 43, 101, and 104; SEQ ID NOS: 21, 27, 44, 61, 67, and 86; and SEQ ID NOS: 21, 27, 44, 101, and 105 (“Protein 10H…SEQ ID NO: 5…6E…SEQ ID NO: 6…A4…SEQ ID NO: 2…E1…SEQ ID NO: 3” pages 9-10). See SEQ ID NOS: 2-3 and 5-6 of Williams comprising at least one combination of CDR sequences claimed with 100% identity match. Williams teaches the name and reference of scFv-A4 (SEQ ID NO: 3 with corresponding CDRs SEQ ID NOS: 21, 26, 43, 62, 66, 85, 101 and 104), scFv-l0H (SEQ ID NO: 2 with corresponding CDRs SEQ ID NOS: 21, 25, 42, 61, 65, 84) and scFv-El (SEQ ID NO: 4 with corresponding CDRs SEQ ID NOS: 21, 27, 44, 61, 67, 86, 101 and 105) (para. 88 of Williams).
It does not appear to be the case that the active steps recited, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. See also MPEP 2106.05(g).
Appending a generic, routine, and obvious post-solution treatment step does not provide a sufficient inventive concept to satisfy § 101. As was the case in Mayo and Ariosa, the method claims at issue here amount to "nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients" using "conventional steps, specified at a high level of generality." Mayo, 132 S. Ct. at 1298, 1300; Ariosa, 788 F.3d at 1377-78.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception into practical application thereof, or amount to significantly more than the judicial exception.
Maintained Rejections
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.
Claims 1, 3 and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Sierks et al. (US 20190010504 A1)-Cite No. A on PTO 892 5/9/2025 ("Sierks").
Regarding claims 1, 3 and 7, Sierks suggests a method of diagnosing a subject with frontotemporal dementia (FTD) (“increasing evidence also implicates oligomeric forms of tau as having a direct role in disease pathogenesis of AD and other tauopathies such as Frontotemporal Dementia (FTD)” paragraph 3, “these reagents can be used to detect the presence of biomarkers which can readily detect and distinguish many related neurodegenerative diseases including…FTD” paragraph 55) the method comprising: obtaining the biological sample from the subject and the subject is believed to be at risk or afflicted with FTD, contacting a biological sample from a subject at risk or suspected of having FTD, wherein the subject is believed to be at risk or afflicted with FTD, with one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TAR DNA-binding protein 43 (TDP-43) variants and/or tau variants, wherein the one or more scFvs is reactive with one or more oligomeric beta amyloid variants (“one exemplary ELISA, ligands (e.g., scFvs) are immobilized … Then, a test composition suspected of containing a target oligomer, such as a clinical sample (e.g., a biological sample obtained from the subject), is added to the wells” paragraph 123, “to this proposal, we show that we can not only detect the presence of toxic oligomeric morphologies of Aβ, tau and a-syn in ante-mortem human serum samples, but that there is a very distinct spike in oligomeric Aβ species in serum many years prior to diagnosis of AD, and even several years prior to diagnosis of mild-cognitive impairment (MCI) suggesting that we can presymptomatically diagnose AD by analysis of serum samples many years before symptoms of AD occur” paragraph 66), wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 and wherein the light chain complementary determining region (CDR) and heavy chain CDR of the one or more scFvs have 100% sequence identity to any one of SEO ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114: (“antibody fragments described herein…SEQ ID NO: 38” paragraph 15, see sequence in page 18). Note that SEQ ID NO: 38 is 93.4% matched to SEQ ID NO: 8 (Applicant’s elected species). Note that SEQ ID NO: 38 of Sierks comprises the CDRs of SEQ ID NOS: 21, 61 and 101 with 100% identity match. Sierks further teaches detecting binding between the one or more scFvs and the biological sample, and wherein the detection of binding between the one or more scFvs to the biological sample is indicative that the subject has or is likely to develop FTD (“the diagnostic methods of the invention, the compositions or ligand of the invention (e.g. binding molecule such as… antibody fragment) may be conjugated to a detecting reagent that facilitates detection of the ligand” paragraph 106, “the bound antigen may be detected. Detection is generally achieved by the addition of an antibody that is linked to a detectable label” paragraph 123). Sierks further teaches that “[n]umerous recent studies suggest that specific protein variants including selected oligomeric forms of these proteins are involved in neuronal toxicity and can interfere with important functions including long term potentiation” (paragraph 52).
Sierks teaches all the limitations of claim 1 but Sierks does not do so in a manner consistent with anticipation, i.e., there is some picking and choosing involved to arrive at the scFv (instant SEQ ID NO: 8) from the list of disclosed scFvs at paragraph 15 of Sierks.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to choose SEQ ID NO: 8 (Applicant’s elected species) from the list of single-chain variable fragments taught by Sierks because Sierks teaches a finite list of possible predictable solutions to the problem of diagnosing FTD, thereby motivating a person having ordinary skill in the art to try picking SEQ ID NO: 8 from said finite list. A person having ordinary skill in the art would have had a reasonable expectation of success because Sierks shows the amino acid sequence and teaches that there has been numerous studies suggesting that specific protein variants are involved in neuronal toxicity.
Regarding claims 5-6, Sierks teaches wherein the biological sample is a fluid sample, wherein the biological sample is a sera sample (“the samples…are blood product samples” paragraph 31, “the blood product is serum” paragraph 32).
Regarding claim 8, Sierks teaches wherein the method is performed utilizing an enzyme linked immunosorbent assay (ELISA) (“the protein levels are detected by means of ELISA” paragraph 36).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Sierks as applied to claim 1 above, and further in view of Veiga et al. (EP 3376230 A1) (“Veiga”).
Sierks addresses the method of claim 1 as discussed above.
Sierks fails to teach further comprising administering a treatment to the subject diagnosed with FTD to treat one or more symptoms associated with FTD.
Veiga teaches “diagnostic methods for differentiating Alzheimer's Disease (AD) patients
and Frontotemporal Dementia (FTD) patients versus Healthy Controls….and… a method for determining the efficacy of …FTD therapy” (Abstract). Veiga further teaches administering a treatment to the subject diagnosed with FTD to treat one or more symptoms associated with FTD (“Patients diagnosed with FTD might be treated with drugs aimed to reduce symptomatology… For patients with language variants of FTD, speech therapy is recommended” paragraph 52). Veiga further teaches that FTD “is the second most prevalent dementia of patients below age 65” (paragraph 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Sierks to include administering a treatment to the subject diagnosed with FTD to treat one or more symptoms associated with FTD taught by Veiga because Veiga suggests that a particular treatment is effective and teaches that FTD is the second most prevalent dementia of patients below age 65. A person having ordinary skill in the art would have had a reasonable expectation of success because both Sierks and Vega teach methods of diagnosing FTD.
New Rejections
Claims 10, 12 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Sierks et al. (US 20190010504 A1) ("Sierks") in view of Veiga and Sierks and Williams (US 20160320412 A1)-Cite No. 1 of IDS 1/12/2024 (“Williams”).
Regarding claims 10, 12, 14-16 Sierks suggests a method of diagnosing a subject with frontotemporal dementia (FTD) (paragraphs 3, 55) the method comprising: one or more single-chain variable fragments (scFvs) at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants, wherein the one or more scFvs is reactive with one or more oligomeric beta amyloid variants (paragraphs 66 and 123), wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 (paragraph 15, see sequence in page 18). Note that SEQ ID NO: 38 is 93.4% matched to SEQ ID NO: 8 (Applicant’s elected species). Note that SEQ ID NO: 38 of Sierks comprises the CDRs of SEQ ID NOS: 21, 61 and 101 with 100% identity match. Sierks further teaches and detecting binding between the one or more scFvs and the biological sample (paragraphs 106, 123). Sierks further teaches that “[n]umerous recent studies suggest that specific protein variants including selected oligomeric forms of these proteins are involved in neuronal toxicity and can interfere with important functions including long term potentiation” (paragraph 52).
Sierks fails to teach monitoring a subject with FTD and obtaining and contacting a first biological sample wherein the biological sample is a fluid sample, wherein the fluid sample is a sera sample, from a subject diagnosed with FTD with scFvs and wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of: SEQ ID NOS: 21, 24, 41, 61, 64, and 83; SEQ ID NOS: 21, 24, 41, 101, and 103; SEQ ID NOS: 21, 25, 42, 61, 65, and 84; SEQ ID NOS: 21, 26, 43, 62, 66, and 85; SEQ ID NOS: 21, 26, 43, 101, and 104; SEQ ID NOS: 21, 27, 44, 61, 67, and 86; SEQ ID NOS: 21, 27, 44, 101, and 105; SEQ ID NOS: 21, 28, 45, 61, 68, and 87; SEQ ID NOS: 21, 28, 45, 101, and 106; SEQ ID NOS: 22, 29, 46, 61, 69, and 88; SEQ ID NOS: 22, 29, 46, 101, and 107; SEQ ID NOS: 23, 30, 47, 63, 70, and 89; SEQ ID NOS: 23, 30, 47, 102, and 108; SEQ ID NOS: 21, 31, 48, 61, 71, and 90; SEQ ID NOS: 21, 31, 48, 101, and 109; SEQ ID NOS: 21, 32, and 49; SEQ ID NOS: 21, 27, 50, 61, 72, and 91; SEQ ID NOS: 21, 26, 51, 61, 73, and 92; SEQ ID NOS: 21, 26, 51, 101, and 110; SEQ ID NOS: 21, 33, 52, 61, and 74; SEQ ID NOS: 21, 33, 52, 101, and 111; SEQ ID NOS: 21, 34, 53, 61, 75, and 93; SEQ ID NOS: 21, 34, 53, 101, and 112; SEQ ID NOS: 21, 35, 54, 61, 76, and 94; SEQ ID NOS: 21, 35, 54, 101, and 113; SEQ ID NOS: 21, 36, 55, 61, 77, and 95; and SEQ ID NOS: 21, 36, 55, 101, and 114.
Veiga teaches teach monitoring a subject with FTD and obtaining and contacting a first biological sample wherein the biological sample is a fluid sample, wherein the fluid sample is a sera sample, from a subject diagnosed with FTD with scFvs (“the invention relates to a method for monitoring the progression of a subject suffering from AD or FTD comprising determining in a biological sample of a subject, over the course of a therapy or not, the levels of at least one metabolic marker or markers described in table 1 and table 2” paragraph 124, “Test compounds further include, for example, antibodies (e.g., … humanized, anti-idiotypic, chimeric, and single chain antibodies as well as Fab, F{ab') 2, Fab expression library fragments, and epitope-binding fragments of antibodies)” paragraph 102, “The sample can be isolated from any suitable biological tissue or fluid such as, for example, blood, blood plasma, serum, cerebral spinal fluid (CSF), urine, amniotic fluid, lymph fluids…” paragraph 58). Veiga further teaches that FTD “is the second most prevalent dementia of patients below age 65” (paragraph 4).
Williams teaches “diagnostic tests to distinguish between different pre-symptomatic neurodegenerative diseases” (Abstract). Williams further teaches that “[t]here are currently no reliable physical diagnostic tests to distinguish between different pre-symptomatic neurodegenerative diseases” (para. 5). Williams further teaches that “the capture agent is scFv-A4 (Zameer, A., et al…)… scFv-l0H (Emadi, S.,et al….)… or scFv-El (Kasturirangan, S., et al….)” (para. 88). Williams further teaches wherein the sequence of the light chain complementary determining region (CDR) and heavy chain CDR of the scFv comprises at least one combination selected from the group consisting of: SEQ ID NOS: 21, 24, 41, 61, 64, and 83; SEQ ID NOS: 21, 24, 41, 101, and 103; SEQ ID NOS: 21, 25, 42, 61, 65, and 84; SEQ ID NOS: 21, 26, 43, 62, 66, and 85; SEQ ID NOS: 21, 26, 43, 101, and 104; SEQ ID NOS: 21, 27, 44, 61, 67, and 86; and SEQ ID NOS: 21, 27, 44, 101, and 105 (“Protein 10H…SEQ ID NO: 5…6E…SEQ ID NO: 6…A4…SEQ ID NO: 2…E1…SEQ ID NO: 3” pages 9-10). See SEQ ID NOS: 2-3 and 5-6 of Williams comprising at least one combination of CDR sequences claimed with 100% identity match. Williams further teaches that their “system measures the oligomeric content of … abeta… Tau or TDP-43 (thought to play a role in …Frontotemporal dementia)” (para. 205). Williams further teaches that “[o]verall, our phage capture ELISA system was beneficial in the detection of the oligomeric content in different neurodegenerative diseases” (para. 244).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Sierks to rely on the monitoring a subject with FTD and obtaining and contacting a first biological sample, wherein the biological sample is a sera sample from a subject diagnosed with FTD taught by Veiga because Veiga teaches that FTD is the second most prevalent dementia of patients below 65, and suggests that the monitoring can also enable the monitoring of the course of therapy in these patients. A person having ordinary skill in the art would have had a reasonable expectation of success because both Sierks and Vega teach methods related to biomarkers of FTD.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Sierks in view of Veiga to rely on the scFv comprising at least one combination selected from the group in claim 10 taught by Williams because Williams teaches that these CDR combinations help distinguish between different neurological diseases, which is a current need in the field. A person having ordinary skill in the art would have had a reasonable expectation of success because Williams teaches the name and reference of the scFv. Furthermore, both Sierks and Williams teach scFvs comprising the CDRs of SEQ ID NOS: 21, 61 and 101 with 100% identity match, for detecting amyloid beta, TDP-43 and/or tau in in the context of neurodegenerative diseases and frontotemporal dementia.
Regarding claim 17, Sierks in view of Veiga and Williams teach the method of claim 10 as discussed above.
Sierks further teaches wherein the method is performed utilizing an enzyme linked immunosorbent assay (ELISA) (“the protein levels are detected by means of ELISA” paragraph 36).
Regarding claim 18, Sierks in view of Veiga and Williams teach the method of claim 10 as discussed above.
Sierks further teaches one or more scFvs at least reactive with one or more oligomeric beta amyloid variants, TDP-43 variants and/or tau variants, wherein the one or more scFvs has an amino acid sequence with at least 85% sequence identity to a sequence set forth in any one of SEQ ID NOS: 1-15 and wherein the light chain complementary determining region (CDR) and heavy chain CDR of the one or more scFvs have 100% sequence identity to any one of SEO ID NOS: 21-36, 41-55, 61-77, 83- 95, and 101-114: (see citations above).
Sierks in view of Veiga and Williams further suggest administering a treatment to the subject diagnosed with FTD; obtaining a second biological sample from the subject; contacting the second biological sample with scFvs and detecting the binding between one or more scFvs and the second biological sample (“the invention relates to a method for monitoring the progression of a subject suffering from AD or FTD comprising determining in a biological sample of a subject, over the course of a therapy or not, the levels of at least one metabolic marker or markers described in table 1 and table 2” paragraph 124 of Veiga). Note that although Veiga fails to use the language “administering a treatment” or “second biological sample”, the teachings of “over the course of a therapy” inherently addresses these limitations.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive.
Regarding the 112a rejections,
Applicant argues that “Table 3 and paragraph [0071], expressly discloses the CDR sequences for these scFvs and the particular combinations of CDRs now recited in claims 1 and 10. The skilled artisan would understand that the CDR combinations listed in claim 10 correspond to the actual scFv constructs described and exemplified in the application. By requiring that each CDR of the claimed scFvs be identical to the disclosed CDR sequences, the claims define a genus that is nothing more than the set of scFvs actually disclosed, rather than an open-ended class of theoretical antibodies” (page 6 last paragraph and page 7 para. 1).
However, claim 1 does not recite any combination of CDRs, therefore, the claim encompasses a genus of antibodies for which there is not sufficient written description in the specification. Claim 10, while reciting specific combinations of CDRs, these are not claimed in a way that assigns each CDR combination to their corresponding scFv as disclosed in Table 3. Therefore, claim 10 encompasses a genus of antibodies that have not been properly described such that a person having ordinary skill in the art would question whether Applicant was in possession of the claimed invention (see the complete analysis above).
Regarding the 112b rejections,
Applicant argues that “Because the CDR sequences are now expressly set forth in the claims by SEQ ID NO, the concern that "the claims do not recite the sequence of SEQ ID NOs of the CDR sequences" has been fully resolved” (page 7 para. 6).
However, the amendments necessitate new grounds of rejection (see 112b rejection above).
Regarding the 101 rejections,
Applicant argues that “These engineered scFvs do not exist in nature and are structurally defined in the claims by their CDR sequences. The claimed methods thus recite a concrete laboratory technique using man-made molecules, rather than simply "observing" a natural relationship…the claims require performing a specific laboratory assay, contacting a biological sample with structurally defined, non-naturally-occurring scFvs and detecting binding, so the focus of the claim is the practical application, not the correlation itself” (page 8 para. 2).
However, although the claim recites the one or more of scFvs, these do not particularly or directly apply, rely on or use the natural correlation such that it imposes a meaningful limit on the judicial exception (see 101 rejection above). These limitations merely limit the scFvs used in the natural correlation and therefore are insignificant presolution activity. Similarly, the contacting and detecting steps are drawn to data gathering and fail to integrate the judicial exception into a practical application.
Applicant further argues that “The Office Action does not identify any evidence that scFvs having CDR sequences with 100% identity to SEQ ID NOS: 21-36, 41-55, 61-77, 83-95, and 101-114 were routinely or conventionally used at the time of the invention to detect TDP-43 variants… Here, there is no factual support that the particular scFvs defined by the recited CDR sequences, or methods of diagnosing or monitoring FTD using those scFvs, were well-understood, routine, and conventional at the time the invention was made and the application was filed” (page 8 para. 4 and page 9 para. 1).
However, the amendments necessitate new grounds of rejection (see 101 rejection above). Sierks, Golde and Williams all teach the scFvs having CDR sequences with 100% identity to any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83-95, and 101-114 as claimed. Williams further teaches the name and reference of scFv-A4 (SEQ ID NO: 3 with corresponding CDRs SEQ ID NOS: 21, 26, 43, 62, 66, 85, 101 and 104), scFv-l0H (SEQ ID NO: 2 with corresponding CDRs SEQ ID NOS: 21, 25, 42, 61, 65, 84) and scFv-El (SEQ ID NO: 4 with corresponding CDRs SEQ ID NOS: 21, 27, 44, 61, 67, 86, 101 and 105) (para. 88 of Williams). It does not appear that the additional elements amount to nothing more than what was well-understood, routine and conventional at the time. Therefore, the additional elements fail to add significantly more. See the rejection above for the full 101 analysis.
Regarding the 103 rejections,
Applicant argues that “The Cited References Do Not Teach or Suggest All Claim Elements… As shown in this alignment, SEQ ID NO: 8 and Sierks' SEQ ID NO: 38 differ at multiple amino acid residues, and each of these substitutions occurs within one of the six CDRs (three heavy-chain CDRs and three light-chain CDRs). No substitutions occur in the framework regions… The prior art provides no teaching or suggestion that substituting Sierks' CDR residues with those of SEQ ID NO: 8, or with the other CDR sequences now recited in claims 1 and 10, would retain or improve binding to the particular oligomeric beta amyloid, TDP-43, and tau variants relevant to FTD, much less that such substitutions would have been predictable to the skilled artisan” (page 10 para. 1 and pages 11 paras. 1-2)
However, Sierks does teach the CDRs claimed “any one of SEQ ID NOS: 21-36, 41-55, 61-77, 83-95, and 101-114” (claim 1). Applicant admits that Sierks teaches SEQ ID NOS: 21 and 61 (see alignment in page 10 of the Remarks). Sierks also teaches SEQ ID NO: 101 (see “GFTFSSY” in the alignment shown in the Remarks). Regarding claim 10, new grounds of rejection are set forth in view of Williams-Cite No. 1 of IDS 1/12/2024 who does teach scFv-A4 (SEQ ID NO: 3 with corresponding CDRs SEQ ID NOS: 21, 26, 43, 62, 66, 85, 101 and 104), scFv-l0H (SEQ ID NO: 2 with corresponding CDRs SEQ ID NOS: 21, 25, 42, 61, 65, 84) and scFv-El (SEQ ID NO: 4 with corresponding CDRs SEQ ID NOS: 21, 27, 44, 61, 67, 86, 101 and 105) (para. 88 of Williams). A proper obviousness analysis is set forth above (see 103 rejection above) stating a motivation and reasonable expectation of success.
Applicant further argues that “Veiga does not remedy the disclosure deficiencies of Sierks” (page 12 para. 1).
However, there are no deficiencies in the new grounds of rejection set forth above.
Conclusion
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/Fernando Ivich/Examiner, Art Unit 1678
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677