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 .
Information Disclosure Statement
The information disclosure statements (IDS) filed 11/12/2025, 03/27/2025, 01/30/2025, 01/22/2025, and 09/24/2024 have been considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is claims benefit of foreign application EUROPEAN PATENT OFFICE (EPO) 23176874.8 filed 06/01/2023. Based on the filing receipt, the effective filing date of this application is June 1, 2023 which is the filing date of EPO 23176874.8 from which the benefit of priority is claimed.
Status of Claims
Claims 1-20 are pending and examined herein.
Claim Objections
Claims 1, 3-8, 10-11, 13, 16-20 are objected to because of the following informalities:
Claim 1’s preamble recites, “A method, comprising:”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claims 10 and 13 depend on claim 1.
Claim 3’s preamble recites, “A method, comprising:”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claim 16 depends on claim 3.
Claim 4’s preamble recites, “A mammalian antibody binding specifically to ZSCAN5”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claim 17 depends on claim 4.
Claim 5’s preamble recites, “A carrier, comprising:”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claims 6, 9, and 18 depend on claim 5.
Claim 7’s preamble recites, “A kit, comprising:”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claims 19-20 depend on claim 7.
Claim 7 recites, “and the kit further comprises a means for detecting a mammalian antibody.”. The claim should recite, “and the kit further comprises a means for detecting a mammalian antibody.”.
Claim 8 recites, “a carrier a solid phase comprising”. The claims should recite, “a carrier comprising a solid phase comprising”.
Claim 11’s preamble recites, “An ex vivo method, comprising:”. A claim preamble conventionally sets the intended use or purpose of the claimed invention, which should match the body of the claim.
Claim 13 recites, “consisting ofwhole blood, plasma, serum, cerebrospinal fluid and saliva”. The claim should recite, “consisting of whole blood, plasma, serum, cerebrospinal fluid and saliva”.
Claim 16 recites, “The method according to claim 3, wherein the binding of the antibody is detected in a quantitative manner,”. The claim recites, “The method according to claim 3, wherein the binding of the antibody is detected in a quantitative manner[[,]].”.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
The limitation “a means for capturing an antibody” in claim 7” is interpreted as meaning functionally equivalent to “a molecule binding specifically to the antibody to be immobilized and capable of immobilizing it, either because it is immobilized itself or configured for immobilization, preferably via an affinity tag”. See p. 24 of the applicant’s specification.
The limitation “a means for detecting a mammalian antibody” in claims 7 and 8 is interpreted as meaning functionally equivalent to “a molecule binding specifically to the antibody and allowing detection, typically comprising a detectable label”. See p. 24 of the applicant’s specification.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitations are:
The limitation “the at least one polypeptide and the carrier are configured for immobilizing the at least one polypeptide on a surface of the carrier” in claims 7 and 20.
The limitation “the carrier and a means for capturing an antibody are configured for immobilizing the means for capturing an antibody on the surface of the carrier” in claims 7 and 8.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The limitation “the at least one polypeptide and the carrier are configured for immobilizing the at least one polypeptide on a surface of the carrier” in claims 7 and 20 is interpreted as meaning functionally equivalent to “a molecule bound to a solid carrier insoluble in an aqueous solution, more preferably via a covalent or non-covalent bond, electrostatic interactions, encapsulation, unspecific absorption, printing or entrapment, for example by denaturing a globular polypeptide in a gel, or via hydrophobic interactions, most preferably via one or more covalent bonds”. See p. 11-12 of the applicant’s specification.
The limitation “the carrier and a means for capturing an antibody are configured for immobilizing the means for capturing an antibody on the surface of the carrier” in claims 7 and 8 is interpreted as meaning functionally equivalent to “a molecule bound to a solid carrier insoluble in an aqueous solution, more preferably via a covalent or non-covalent bond, electrostatic interactions, encapsulation, unspecific absorption, printing or entrapment, for example by denaturing a globular polypeptide in a gel, or via hydrophobic interactions, most preferably via one or more covalent bonds”. See p. 11-12 of the applicant’s specification.
If applicant does not intend to have these limitations interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitations to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed function so as to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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, 5-16, and 18-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
Claims 1-3, 5-16, and 18-20 are directed to methods and products comprising “one polypeptide comprising at least one epitope of ZSCAN5 or a variant thereof” and “a mammalian antibody binding specifically to ZSCAN5 or a variant thereof”. The claims are directed at polypeptides comprising at least one epitope of ZSCAN5, including their variants, without any limitation on size or origin.
The scope of the claims therefore covers methods and products for using a large genus of polypeptides and variants thereof characterized by substantial variability.
Regarding the predictability or unpredictability in the art, Nishimura (“Genetic Variants in C5 and Poor Response to Eculizumab”, published 2014) teaches that an antigen variant with one amino acid residue change disrupts antibody binding (see, e.g., p. 632, under “ABSTRACT”, under “CONCLUSIONS”). The broad genus of polypeptides and variants thereof includes changes to the epitope, affecting antibody binding.
The specification does not disclose actual reduction to practice of sufficient polypeptides and variants thereof having the necessary functional characteristics. The specification only discloses three variants of ZSCAN5 (see. p. 87, under “Identification of ZSCAN5B, ZSCAN5C, and ZSCANA as the target of neuronal autoantibodies”). The specification merely suggests art-recognized methods of making polypeptides and variants thereof and provides prophetic examples; there is insufficient disclosure of specific species of polypeptides and variants thereof falling within the claimed genus.
The disclosure general methods that might be used to make polypeptides and variants thereof is insufficient to describe the claimed genus of polypeptides and variants thereof. The Federal Circuit addressed an analogous situation in University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004), finding that disclosure of “assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product,” did not satisfy the written description requirement for claims requiring administration of a “compound that selectively inhibits PGHS-2.” Rochester, 119 F.3d at 918, 927; see also Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344 (Fed. Cir. 2010) (recognizing distinction between requirements for written description and enablement).
Furthermore, there is also no disclosure of any partial structure common to the members of the genus of polypeptides and variants thereof that would correlate with function (in this case, the claimed function of selectively binding to the mammalian antibody specific for ZSCAN5).
The importance of structure/function correlations was recently highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centocor Biologics, App. No. 2013-1338, -1346 (Fed. Cir., July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either 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. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " 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. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). 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).
If it was indeed unpredictable at the time of the invention to develop polypeptides and variants thereof as applicant has argued, then one skilled in the art would not envision possession of the entire genus of polypeptides and variants thereof as claimed since the specification merely suggests art-recognized methods of making polypeptides and variants thereof and provides minimal examples.
There is no partial structure or other identifying characteristics disclosed, common to the members of the genus of polypeptides and variants thereof having sufficiently high binding affinity, that would allow one skilled in the art to envision that the applicant has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.
For all of these reasons, the specification does not demonstrate possession of the entire genus of polypeptides and variants thereof having the claimed functional characteristics of selectively binding to mammalian antibodies specific to ZSCAN.
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 2, 5, 8, 10, and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites the limitation "separating the complex formed in step a) from the sample" in “step c)” of the claim. There is insufficient antecedent basis for this limitation in the claim. “step a)” does not contain “a complex”. Therefore, the metes and bounds of the claim cannot be ascertained. For the purpose of applying prior art, the step will be interpreted to mean "separating the complex formed in step b) from the sample" because “step b)” contains “a complex”.
Regarding claims 5 and 8, the claims recite, “at least one additional diagnostically useful antigen”. However, it is unclear what antigens are “diagnostically useful”. The specification fails to ameliorate the lack of clarity. Therefore, the metes and bounds of the claims cannot be ascertained.
Regarding claim 10, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 4, 8, and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Under the MPEP, 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.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Natural Laws:
Claim 8 recites, “having an increased risk of suffering from or developing a disease associated with the presence of the mammalian antibody according to claim 4”.
The claim is directed to the natural relationship/correlation between a mammalian antibody binding specifically to ZSCAN5 and the increased risk of suffering from or developing a disease.
The natural correlation set forth above is considered a judicial exception/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 biomarkers 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 presence of the mammalian antibody binding specifically to ZSCAN5 and the increased risk of suffering from or developing a disease. The presence of the mammalian antibody binding specifically to ZSCAN5 correlates with the increased risk of suffering from or developing a disease without any human action.
The presence of the mammalian antibody binding specifically to ZSCAN5 and the increased risk of suffering from or developing a disease is a judicial exception as it exists in principle apart from any human action; the relationship itself therefore cannot form the basis for eligibility.
Natural Products:
Claim 4 and 17 are directed to a natural product, “a mammalian antibody”. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception – i.e., as drafted, the claims read upon a product of nature for the following reasons:
Claims 4 and 17 are drawn to a composition formed entirely from natural components (as disclosed on p. 3, lines 4-6 of the instant specification). The claimed composition is not markedly different from its naturally-occurring counterpart because there is no indication that the composition has any characteristics or properties that are different from the naturally-occurring counterpart.
Abstract Ideas:
Claim 8 is directed towards “identifying a patient”.
The claim limitations of identifying patients may be categorized as an abstract idea, namely mental processes/concepts performed in the human mind. The claims, under its broadest reasonable interpretation, covers performance of identifying patients solely within the human mind, or by a human using pen and paper. Therefore, identifying patients represents an abstract idea.
Step 2A, Prong 2
The above-discussed element of identifying patients is insufficient to integrate the judicial exception into a practical application because steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application. In this case, identifying patients represents a judicial exception and not a practical application thereof.
Claim 8 also recites “providing” a mammalian antibody or a polypeptide or a carrier or a kit. Such limitations on the method are insufficient to integrate the judicial exceptions because the purpose is merely to obtain data, specifically data on the presence of the mammalian antibody specific for ZSCAN5. This 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).
Claims 4 and 17 also do not integrate the composition into a distinguishing practical application (for example, do not broadly or specifically recite dosage forms and the therapeutically-effective amounts of the material), but merely recite the natural materials themselves. Claim 17 merely adds that the mammalian antibody is in a liquid without any practical use of the antibody in the liquid. The liquid does not expressly have any effect on the antibody. Therefore, the liquid does not transform the judicial exception into a practical application.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
The additional elements of claim 8, including the limitations of providing reagents, such as antibodies, polypeptides, carriers, and kits, for the method, do not add significantly more to the judicial exception. The steps are routine and conventional data gathering, which is not contributing an inventive concept. Therefore, the additional elements of claim 8 do not add an inventive concept.
Claims 4 and 17 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any additional elements, besides the antibody being placed in a liquid.
Therefore, the claimed composition is not deemed to be markedly different from what exists in nature in terms of structural and/or functional differences. In other words, the claims do not set forth a marked difference in terms of structural and/or functional differences (properties and/or characteristics) as compared to the naturally-occurring counterparts (see, e.g., Diamond v. Chakrabarty, 447 U.S. 303(1980)).
Thus, when the relevant factors are analyzed, they weigh against a significant difference between the claimed invention and a judicial exception. Therefore, the claimed invention is not considered to be patent eligible subject matter.
For all of these reasons, claims 4, 8, and 17 fail to include additional elements that are sufficient to amount to significantly more than the judicial exceptions.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 7-17, and 19-20 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Nagele (US 20200309795 A1, published 2020-10-01, cited in IDS filed 2020-10-01).
With respect to claim 1, Nagele teaches a method of detecting in a sample a mammalian antibody binding specifically to ZSCAN5 (see, e.g., para. [0012]-[0013]: “described herein is the use of these diagnostic biomarkers to accurately detect and diagnose AD based on their detection, identification and quantification revealed through interactions with their respective antigen targets on protein microarrays […] Protein antigens that have been identified as capable of being specifically bound by the AD diagnostic biomarkers are set forth in the following Table 1”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”).
With respect to claim 2, Nagele teaches a method for isolating a mammalian antibody binding specifically to ZSCAN5, comprising:
a) immobilizing on a carrier at least one polypeptide comprising at least
one epitope of ZSCAN5 or a variant thereof,
b) contacting a sample comprising antibodies with the at least one
polypeptide under conditions compatible with formation of a complex,
wherein said antibody binds to said polypeptide,
c) separating the complex formed in step b) from the sample (see, e.g., step a) – para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and para. [0019]: “The individually addressable autoantigens are preferably immobilized on the surface to form an array. The substrates may be used in suitable shapes, such as films, sheets, or plates, or may be coated onto or bonded or laminated to appropriate inert carriers, such as paper, glass, plastic films, or fabrics”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”; step b) – para. [0017]: “Assays to determine the presence or absence of one or more AD diagnostic biomarkers in the biological sample are performed by contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form, and detecting the presence of the immunocomplex”, and para. [0097]: “identify autoantibodies in human sera”; step c) - para. [0019]: “The individually addressable autoantigens are preferably immobilized on the surface to form an array”, and para. [0017]: “contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form”). It is understood that contacting the antibodies in the sample with the immobilized autoantigen, ZSCAN5, will separate the antibodies from the sample by forming a complex.
With respect to claim 3, Nagele teaches A method, comprising:
contacting a polypeptide comprising at least one epitope of ZSCAN5 or a variant thereof with a liquid comprising a mammalian antibody binding specifically to ZSCAN5, wherein a candidate drug is present, and detecting binding of the antibody (see, e.g., para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”, and para. [0017]: “Assays to determine the presence or absence of one or more AD diagnostic biomarkers in the biological sample are performed by contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form, and detecting the presence of the immunocomplex”, and para. [0034]: “The results of the assay provide an AD diagnostic biomarker profile for the patient that is useful to diagnose AD and optimize a treatment regimen for AD”).
With respect to claim 4, Nagele teaches a mammalian antibody binding specifically to ZSCAN5 (see, e.g., para. [0013]: “AD diagnostic biomarkers are defined herein as antibodies that specifically bind to protein antigens and are diagnostic indicators that can be used to differentiate Alzheimer's Disease from control subjects without AD. The term “protein antigens” as used herein includes protein and peptide antigens. Protein antigens that have been identified as capable of being specifically bound by the AD diagnostic biomarkers are set forth in the following Table 1”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”).
With respect to claim 5, Nagele teaches A carrier, comprising:
a solid phase comprising at least one immobilized polypeptide comprising at least
one epitope of ZSCAN5 or a variant thereof and a) a negative and/or positive control (see, e.g., solid phase comprising immobilized epitope of ZSCAN5 - para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and para. [0019]: “The individually addressable autoantigens are preferably immobilized on the surface to form an array. The substrates may be used in suitable shapes, such as films, sheets, or plates, or may be coated onto or bonded or laminated to appropriate inert carriers, such as paper, glass, plastic films, or fabrics”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”; positive or negative control – para. [0031]: “Data may be normalized by comparing median values of multiple identical control spots in different regions of the same array”).
With respect to claim 7, Nagele teaches (see, e.g., para. [0010]: “the present invention provides a kit for detecting AD-specific antibodies”, and para. [0042], and para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and para. [0019]: “The individually addressable autoantigens are preferably immobilized on the surface to form an array. The substrates may be used in suitable shapes, such as films, sheets, or plates, or may be coated onto or bonded or laminated to appropriate inert carriers, such as paper, glass, plastic films, or fabrics”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”).
With respect to claim 8, Nagele teaches a method of identifying a patient having an increased risk of suffering from or developing a disease associated with the presence of the mammalian antibody according to claim 4, the method comprising: the combination of at least one polypeptide comprising at least one epitope of ZSCAN5 or a variant thereof and a means for detecting a mammalian antibody (see, e.g., para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”, and para. [0016]: “In a preferred embodiment, the subject is a human subject”, and para. [0017]: “Assays to determine the presence or absence of one or more AD diagnostic biomarkers in the biological sample are performed by contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form, and detecting the presence of the immunocomplex”).
With respect to claim 9, Nagele teaches a method of manufacturing the carrier according to claim 5, the method comprising: providing at least one polypeptide comprising at least one epitope of ZSCAN5 or a variant thereof (see, e.g., para. [0023]: “Suitable methods for external production and purification of autoantigens to be spotted on arrays include expression in bacteria”, para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”).
With respect to claim 10, Nagele teaches the method of claim 1, the method comprising: a mammalian antibody binding specifically to ZSCAN5 or a variant thereof (see, e.g., para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”, and para. [0016]: “In a preferred embodiment, the subject is a human subject”, and para. [0017]: “Assays to determine the presence or absence of one or more AD diagnostic biomarkers in the biological sample are performed by contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form, and detecting the presence of the immunocomplex”).
With respect to claim 11, Nagele teaches an ex vivo method, comprising:
removing a mammalian antibody binding specifically to ZSCAN5 or a variant thereof from the blood of a mammalian patient, wherein the mammalian antibody is the mammalian antibody according to claim 4 (see, e.g., para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”, and para. [0016]: “In a preferred embodiment, the subject is a human subject”, and para. [0017]: “Assays to determine the presence or absence of one or more AD diagnostic biomarkers in the biological sample are performed by contacting the sample with one or more autoantigens that are specific for an AD diagnostic biomarker under conditions that allow an immunocomplex of the autoantigen and the antibody to form, and detecting the presence of the immunocomplex”, and para. [0097]: “identify autoantibodies in human sera”).
With respect to claim 12, Nagele teaches wherein the polypeptide is a recombinant, isolated and/or purified polypeptide. (see, e.g., para. [0018]: “The autoantigens may be purified from natural sources, or produced recombinantly”).
With respect to claim 13, Nagele teaches wherein the sample is serum (see, e.g., para. [0097]: “identify autoantibodies in human sera”).
With respect to claim 14, Nagele teaches detecting the antibody or complex by labeled immunoassay (see, e.g., para. [0019], and para. [0030]: “label-based detection methods include addition of a secondary antibody that is coupled to an indicator reagent comprising a signal generating compound. The secondary antibody may be an anti-human IgG antibody. Indicator reagents include chromogenic agents, catalysts such as enzyme conjugates, fluorescent compounds such as fluorescein and rhodamine, chemiluminescent compounds such as dioxetanes, acridiniums, phenanthridiniums, ruthenium, and luminol, radioactive elements, direct visual labels, as well as cofactors, inhibitors and magnetic particles. Examples of enzyme conjugates include alkaline phosphatase, horseradish peroxidase and beta-galactosidase”).
With respect to claim 15, Nagele teaches wherein the carrier is selected from the group
consisting of a glass slide, a biochip, a microtiter plate, a lateral flow device, a test
strip, a membrane, a chromatography column and a bead (see, e.g., para. [0019]: “ The individually addressable autoantigens are preferably immobilized on the surface to form an array. The substrates may be used in suitable shapes, such as films, sheets, or plates, or may be coated onto or bonded or laminated to appropriate inert carriers, such as paper, glass, plastic films, or fabrics. In a preferred embodiment, the substrate is a slide or a bead”).
With respect to claim 16, Nagele teaches the binding of the antibody is detected in a quantitative manner (see, e.g., para. [0019]).
With respect to claim 17, Nagele teaches the mammalian antibody is in an artificial buffer (see, e.g., para. [0097]: “serum samples, diluted 1:500 in washing buffer”).
With respect to claim 19, Nagele teaches the kit according to claim 7, wherein the carrier is the carrier according to claim 5 (see, e.g., para. [0010]: “the present invention provides a kit for detecting AD-specific antibodies”, and para. [0042], and para. [0018]: “An autoantigen may comprise a protein antigen of Table 1, or a polypeptide or peptide fragment thereof containing one or more epitopes recognized by the AD diagnostic biomarker, or an epitope peptidomimetic that is recognized by the AD diagnostic biomarker”, and para. [0019]: “The individually addressable autoantigens are preferably immobilized on the surface to form an array. The substrates may be used in suitable shapes, such as films, sheets, or plates, or may be coated onto or bonded or laminated to appropriate inert carriers, such as paper, glass, plastic films, or fabrics”, and p. 6, under “Table 1”, “zinc finger and SCAN domain containing 5 (ZSCAN5)”).
With respect to claim 20, Nagele teaches wherein in the at least one polypeptide and the carrier are configured for immobilizing the at least one polypeptide on a surface of the
carrier via an affinity tag and a ligand binding to the affinity tag, and the at least
one polypeptide comprises a detectable label (see, e.g., para. [0020]: “Biological capture methods utilising a tag (e.g., hexahistidine/Ni-NTA or biotin/avidin) on the protein and a partner reagent immobilized on the surface of the substrate provide a stable linkage and bind the protein specifically and in reproducible orientation”, and para. [0030]: “label-based detection methods include addition of a secondary antibody that is coupled to an indicator reagent comprising a signal generating compound. The secondary antibody may be an anti-human IgG antibody. Indicator reagents include chromogenic agents, catalysts such as enzyme conjugates, fluorescent compounds such as fluorescein and rhodamine, chemiluminescent compounds such as dioxetanes, acridiniums, phenanthridiniums, ruthenium, and luminol, radioactive elements, direct visual labels, as well as cofactors, inhibitors and magnetic particles. Examples of enzyme conjugates include alkaline phosphatase, horseradish peroxidase and beta-galactosidase”).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 6 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Nagele (cited above), as applied to claims 1-5, 7-17, and 19-20 above, and further in view of Stoecker (US 10725035 B2, published 2020-07-28).
Nagele teaches as set forth above, but fails to teach the carrier comprises at least one additional antigen is at least one antigen selected from the group consisting of NMDAR, Lgl1, AMPA1, AMPA2, CASPR2, GABA B, GABA A, DPPX, IGLON5, Hu, Yo, CV2/CRMP5, Ri, Ma2, Amphiphysin, Recoverin, RGS8, DAGLA, STX1B, AK5, AP3B2, Flotillin1+2, GRM1, GRM2, GRM5, GLURD2, ITPR1, KCNA2, NCDN, Septin 3+5+6+7+11, and Sez6L2, as in claims 6 and 18.
However, Stoecker teaches a carrier comprising the additional antigen STX1B, as in claims 6 and 18 (see, e.g., col. 3, lines 13-17: “the problem is solved by a polypeptide comprising a polypeptide selected from the group comprising NSF, STX1B, DNM1 and VAMP2 or a variant thereof, which is preferably immobilized, more preferably on a solid carrier”).
Nagele and Stoecker are analogous to the field of the claimed invention because they are both in the field of autoantibody detection. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to add the additional antigen of Stoecker to the carrier of Nagele. An artisan would have been motivated to do so because Stoecker discloses, “The present invention is based on the inventors' surprising finding that an autoantibody to NSF, an autoantibody to STX1B, an autoantibody to DNM1 and an autoantibody to VAMP2 exist and may be detected in samples from a number of patients suffering from neurological symptoms, but not in samples obtained from healthy subjects” (see, e.g., col. 5, lines 19-24). An artisan would have had a reasonable expectation of success based on the given disclosures.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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