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.
Election/Restrictions
Applicant's election with traverse of Group I, claims 26-35 and 39-40 in the reply filed on 7/24/2026 is acknowledged. The traversal is on the ground(s) that "search and examination of the entire application could be made without serious burden" (page 1 para. 2). This is not found persuasive because the two inventions do not share a technical feature. Thus, a search of one invention would not uncover art related to the other invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 36-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/24/2026.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/JP2022/006450, filed 02/17/2022. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. JP2021-023614, filed on 02/17/2021 in Japan.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements filed on 9/25/2023 and 4/7/2025 are being considered by the examiner.
Claim Objections
Claims 26-35 and 39 objected to because of the following informalities:
In claim 26 line 1, “A method the method comprising:” appears to be a typographical error, namely, it is suggested that “A method the method comprising:” read as “A method, the method comprising:” (adding a comma). Furthermore, it is suggested that the claim includes a preamble to conform with convention. For example, “A method for providing information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis, the method comprising:” (annotations added).
In claim 26 line 2, Applicant uses the abbreviations “GATA2” and “PTPN13”, it is recommended that abbreviations be accompanied by their full meaning at least at the first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claims 27-28 line 1, “the detecting” appears to be a typographical error, namely, it is suggested that “the detecting” read as “wherein the detecting” (annotations added).
In claims 29-31 and 33-35 line 1, “ further the detecting” appears to be a typographical error, namely, it is suggested that “further the detecting” read as “further wherein the detecting” (annotations added).
In claim 29 line 2, Applicant uses the abbreviation “DOC2B”, it is recommended that abbreviations be accompanied by their full meaning at least at the first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claim 30 line 2, Applicant uses the abbreviation “ZP1”, it is recommended that abbreviations be accompanied by their full meaning at least at the first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claim 31 line 2, Applicant uses the abbreviations “FRAT1”, “SLC1A5” and “INADL”, it is recommended that abbreviations be accompanied by their full meaning at least at the first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claim 32 line 1, it is suggested that the claim includes a preamble to conform with convention. For example, “A method, comprising:” should read as “A method for providing information on discrimination of possibilities of morbidities for isolated adrenocorticotropic hormone (ACTH) and lymphocytic adenohypophysitis, the method comprising:” (annotations added).
In claim 33 line 2, Applicant uses the abbreviation “KCNMA1”, it is recommended that abbreviations be accompanied by their full meaning at least at the first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claims 39-40 line 1, “the autoimmune hypothalamic” appears to be a typographical error, namely it is suggested that “the autoimmune hypothalamic” read as “wherein the autoimmune hypothalamic” (annotations added).
In claims 39-40 line 2, “Isolated ACTH deficiency” appears to be a typographical error, namely it is suggested that “Isolated ACTH deficiency” read as “isolated ACTH deficiency” (decapitalizing “I”) as per claim 32.
In claim 40 line 2, “the autoimmune hypothalamic hypophysitis” appears to be a typographical error, namely it is suggested that “the autoimmune hypothalamic hypophysitis” read as “the lymphocytic hypophysitis” as per claim 32.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26-35 and 39-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This is an enablement rejection.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The specification does not reasonably provide enablement for providing information regarding possibility of morbidity for autoimmune hypothalamic hypophysitis (claim 26), let alone providing information on discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis (claim 32).
The specification does not provide sufficient evidence that the claimed method of using the detecting, as an index, of anti-GATA2 antibody and/or anti-PTPN13 antibody is effective for providing information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis or regarding discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis. The evidence provided are immunoblots showing that the serum of one out of three patients with isolated ACTH deficiency weakly reacted with GATA2 antigen, and the sera of two out of the three patients with isolated ACTH deficiency reacted with PTPN13 antigen (one of which reacted very weakly), while the sera of the two healthy controls did not react with the GATA2 and PTPN13 antigens (although the serum of control C-1 appears to be weakly reactive with PTPN13) (see Fig. 2G and 2I). However, these weak reactivities of the sera of patients with isolated ACTH deficiency provide no information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis or on the discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis. Therefore, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement
requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S.261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied.
In re Wands, 858F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation.
In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
In regard to Wands factors (A) and (B), the breadth of the claims needed to enable the invention is determined by whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought in the claims. AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). The propriety of a rejection based upon the scope of a claim relative to the scope of the enablement concerns (1) how broad the claim is with respect to the disclosure and (2) whether one skilled in the art could make and use the entire scope of the claimed invention without undue experimentation.
The nature of the invention is a biological/chemical case, where there is natural unpredictability in performance of certain species other than those specifically enumerated; see MPEP § 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the claimed method(s), with a reasonable expectation of success, because it would not have been predictable from the disclosure that the claimed detection index of anti-GATA2 antibody and/or anti-PTPN13 antibody (along with the rest of the claimed autoantibodies) would function as claimed with respect to providing information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis or regarding discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis (see MPEP § 2164.03).
In regard to Wands factors (C), (D) and (E), the state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains and provides evidence for the degree of predictability in the art; see MPEP § 2164.05(a).
Accordingly, see De Bellis et al. Best Practice & Research Clinical Endocrinology & Metabolism Vol. 19, No. 1, pp. 67–84, 2005 doi:10.1016/j.beem.2004.11.007 (“De Bellis”).
De Bellis teaches that autoimmune hypothalamic hypophysitis is “is frequently associated with other endocrine and non-endocrine autoimmune diseases… The most common association is with Hashimoto’s thyroiditis or Graves’ diseases. Moreover, an association with central diabetes insipidus, type 1 diabetes mellitus, Addison’s disease, hypoparathyroidism, chronic atrophic gastritis, and pernicious anaemia has been described. Less frequently…with systemic lupus erythematosus, autoimmune hepatitis and primary biliary cirrhosis” (page 70 para. 3). Furthermore, De Bellis teaches that autoantibodies associated with autoimmune hypothalamic hypophysitis “can disappear over time; for this reason the time of detection could influence their identification” (page 71 para. 2). De Bellis also teaches that the immunoblot method for detecting the antibodies “is very difficult to standardize” (page 73 para. 2). De Bellis also teaches that “[t]he natural history of LYH [lymphocytic hypophysitis] is very variable, often showing during its course an endless series of reversible changes in its morphological, clinical and immunological characteristics… in some other cases the natural course of LYH is characterized by cycles of remissions and relapses” (page 75 para. 2 and 76 paras. 1-2). De Bellis finally teaches that “APAs [anti-pituitary antibodies] are still not considered good markers of LYH because of various difficulties in methodology and clinical interpretation” (page 80 para. 2).
See also Kacem et al. Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1 DOI:10.4103/2230-8210.119521 (“Kacem”). Kacem teaches that isolated ACTH deficiency may have a genetic origin in neonates and children, whereas “[i]n adults, IAD may appear after a traumatic injury or a lymphocytic hypophysitis (LYH), the latter possibly due to autoimmune etiology” (page S107 col. 1 para. 1). Kacem further teaches that “[a]mong the ‘isolated’ pituitary hormone deficiencies, ACTH deficiency is the earliest and most frequent alteration in patients with LYH. This is present in about 65% of cases”(page S109 col. 2 para. 3).
Given the cited teachings of the prior art that autoimmune hypothalamic hypophysitis is a highly variable disease associated with numerous other autoimmune diseases, and that isolated ACTH deficiency is also associated with other multiple possible origins, the cited references demonstrate that the use of anti-GATA2 antibody and/or anti-PTPN13 antibody for providing information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis or regarding discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis is unpredictable.
While the level of skill in the art is high, the amount of guidance provided regarding how to use the claimed detection index is scant. Accordingly, the amount of experimentation required to determine how to use the recited detection index is quite extensive.
Due to the large quantity of experimentation necessary to determine how to use the recited detecting, as an index, of anti-GATA2 antibody and/or anti-PTPN13 antibody for providing information regarding the possibility of morbidity for autoimmune hypothalamic hypophysitis or regarding discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis, the lack of direction/guidance presented in the specification regarding the same, the absence of working examples directed to the same, the complex nature of the invention, the limited state of the prior art, the unpredictability of the effects of complex biological molecules on diseased physiological systems, and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. §112 first paragraph.
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 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 39 recites “the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency”.
However, “the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency” is not clear. Note that isolated ACTH deficiency, while related to autoimmune hypothalamic hypophysitis, is considered a separate disease (“isolated adrenocorticotropic (ACTH) deficiency (isolated ACTH deficiency, IAD), which is a disease related to LAH” spec. para. 4, “Test method for differentiating lymphocytic adenohypophysitis (LAH) and isolated ACTH deficiency (IAD) para. 44). Therefore, it is not clear how the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency.
Claim 40 recites “The kit according to claim 32…”.
However, claim 32 recites “A method”, not a “kit”. Because of this, a person having ordinary skill in the art would be confused as to what are the metes and bounds of the claim.
Claim 40 further recites “the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency”.
Similar to claim 39, “the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency” is not clear. Note that isolated ACTH deficiency, while related to autoimmune hypothalamic hypophysitis, is considered a separate disease (spec. paras. 4 and 44). Therefore, it is not clear how the autoimmune hypothalamic hypophysitis is Isolated ACTH deficiency.
For these reasons the claims are rejected under 112b.
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 26-35 and 39-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to at least one judicial exception 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).
The claims recite “detecting, as an index, anti- GATA2 antibody and/or anti-PTPN13 antibody in a sample obtained from an individual,” “wherein the index provides information regarding possibility of morbidity for autoimmune hypothalamic hypophysitis” (claim 26) or “wherein the index provides information on discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis” (claim 32).
The natural relationship to which the claims are directed (i.e., the relation between anti- GATA2 antibody and/or anti-PTPN13 antibody and autoimmune hypothalamic hypophysitis or isolated ACTH deficiency and lymphocytic adenohypophysitis) 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 index of anti-GATA2 antibody and/or anti-PTPN13 antibody and the possibility of morbidity of autoimmune hypothalamic hypophysitis or isolated ACTH deficiency and lymphocytic adenohypophysitis.
The correlation between autoantibody 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.
Dependent claims 27-31 and 33-35 further limit the claims to detecting, as the index, other antibodies in the sample. Therefore, claims 27-31 are also directed to the natural correlation between the recited antibodies present in the sample and the disease.
Dependent claims 39-40 further limit the disease to which the natural correlation is directed to. Therefore, claims 39-40 are also directed to the judicial exception.
Step 2A, Prong 2
There are no additional elements. The claims solely describe the judicial exception, i.e. a natural correlation. Therefore, given that there are no additional elements, the claims are not integrated into a practical application.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
As mentioned in step 2A, Prong two above, there are no additional elements. The claims solely recite the judicial exception, i.e. a natural correlation. Therefore, given that there are no additional elements, the claims are not significantly more than the judicial exception.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Smith et al. European Journal of Endocrinology (2012) 166 391–398 DOI: 10.1530/EJE-11-1015 (“Smith”).
Smith teaches that “A number of potential autoantigens have been proposed in lymphocytic hypophysitis including α-enolase (18, 19, 20), neuron-specific enolase (NSE)
(20), GH (21, 22), pituitary gland-specific factors 1a and 2 (PGSF1a and PGSF2) (17), secretogranin II (23) and most recently chromosome 14 open reading frame 166 and chorionic somatomammotropin (24)” (page 392 col. 1 para. 3). Smith further teaches that “[t]his study identified TPIT as a minor target autoantigen in lymphocytic hypophysitis when tested in an
immunoprecipitation assay. A number of other potential autoantigens were found, including CHD8 (a DNA binding protein), Piccolo (a presynaptic cytomatrix protein associated with the active zone) and a CADPS” (page 395 col. 1 para. 4).
However, Smith fails to teach detecting, as an index, anti-GATA2 antibody and/or anti-PTPN13 antibody.
There was no prior art references found that teach detecting, as an index, anti-GATA2 antibody and/or anti-PTPN13 antibody for providing information regarding possibility of morbidity for autoimmune hypothalamic hypophysitis or for providing information on discrimination of possibilities of morbidities for isolated ACTH deficiency and lymphocytic adenohypophysitis.
In fact, Smith seems to teach away from such an index, “[e]ven then, it may not be possible to differentiate the different types of hypophysitis on the basis of autoantibodies alone” (page 395 col. 2 para. 3). Therefore, the claims seem free of the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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