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 .
Claims 8, 10, 12, 15 and 21 have been canceled.
Claims 1-7, 9, 11, 13-14, 16-20 and 22-25 are pending and under examination.
Claim Rejections - 35 USC § 101
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 1-7, 9, 11, 13-14, 16, 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a method of diagnosing or prognosis of pulmonary arterial hypertension (PAH), a method for optimizing therapy for a subject under treatment of PAH, or a method of treating PAH without significantly more. The claim(s) recite(s) judicial exception. This judicial exception is not integrated into a practical application because:
As to claim 1, it is the natural correlation of the natural protein biomarkers with the diagnosis or prognosis by a mental comparing step.
As to claim 2, similarly natural biomarkers measuring with a mental comparison analysis step followed by therapy. As to the preamble “[a] method for optimizing therapy for a subject undergoing treatment for PAH”, and step (c )(i) and (ii) “changing therapy… if increased level” and “maintaining the therapy if level is lower or the same”, the Office would give weight for the therapy in all these three places in view of both BRI and ordinary skilled person in the field. That means the subject is undergoing a therapy (not mere resting) and monitored by the recited biomarkers followed by either maintaining the SAME therapy or change to an alternative therapy should the biomarkers indicating to worse situation, i.e. increased levels. Under scenario (1), maintaining SAME treatment (if no change or less than reference on levels of biomarkers) provides a practical application amounting significantly more than judicial exception. Scenario (2), under normal condition, one clinician would NOT prescribe mere resting when encountering worse condition. A different therapy would be prescribed to ameliorate the condition of subject. This changing therapy would be an active (not mere resting) and constitute a practical application above threshold of judicial exception. However there is lack of particularity for the so-called “therapy”. MPEP § 2106.04(a) instructs:
“a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be “particular,” i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites “administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype.” This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and “administering a suitable medication to a patient.” MPEP § 2106.04(a). Conversely, applicants recite specific PAH treatment choices in claim 20 which is constituted as a practical application weighing significantly more than law of nature.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional of particular specified treatment or medical procedures are recited. Moreover, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because all the sample obtaining, processing and measuring specific natural molecules are common, routine, and well-known in the field, such as microarray, aptamer-based assay or ELISA (Table 1). These steps are recited at a high level of generality, and are necessary data gathering steps that feed into the determining step. One cannot do the determining step without getting the data. This weighs against it being significantly more.
Claims 17-18, the claimed inventions are directed to non-statutory subject matter. The claim(s) do not fall within at least one of the four categories of patent eligible subject matter because the data storage medium can be a compact disk or a carried wave covers a non-statutory embodiment. Similarly, a computer program which causes a processor to perform function in a computer is a software per se without any structure and can be considered transitory signal media (MEPE 2106.03 II). Therefore these two are not eligible for step 1 of 35 USC 101 subject matter eligibility analysis.
Claim Rejections - 35 USC § 112
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 4-7, 9, 11, 13, 20, 24-25 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.
As to claim 3, it is not clear what constitutes “Z-score”, particularly what is difference between “a single protein score” versus “Z-score”. Please clarify.
As to claim 5, MPEP 2173.05(s)“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)” .
As to claim 7, line 3, the wording “preferably” 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).
As to claim 9, line 4, the wording “preferably” 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).
As to claim 11, line 2, the wording “preferably” 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).
As to claim 13, line 4, the wording “preferably” 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).
As to claim 20, the phrase "particularly" 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).
As to claim 24, line 2, the wording “preferably” 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 § 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 22-25 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 issue is on the term “reagents” used for quantification.
Claim 22 requires "reagents for quantification of the two or more biomarkers" and optionally, "an internal control". These reagents are claimed purely by function with no structural information. The internal control has no recited structure as well. Dependent claim 23 requires that these reagents comprise: "(a) one or more aptamer specific for each of the two or more biomarkers; (b) one or more antibody specific for each of the two or more biomarkers; or (c) one or more antibody for at least one of the two or more biomarkers, and one or more aptamer specific for the two or more biomarkers for which an antibody is not provided". Claim 24 requires "reagents for quantification of two or more biomarkers selected from SVEP1, PXDN, renin, NRP1, TSP2 and PRDX4, wherein preferably the kit comprises reagents for the quantification of SVEP1, PXDN, renin, NRP1, TSP2 and PRDX4". Dependent claim 25 requires that the reagents in claim 24 "are for quantification of the two or more biomarkers by an aptamer- based assay or by ELISA; and/or (b) the kit further comprises standards for use in quantifying the two or more biomarkers by an aptamer-based assay or by ELISA". The reagents of claims 24 and 25 and the standards are also structurally undefined.
None of these reagents are defined by any structure within the claims. If one considers a subset of the claimed scope, the antibodies and aptamers to the biomarkers are only claimed by function. It appears that the specification has provided not even one example of either antibody or aptamer within the scope of the claims.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement.
With regard to the scope of the claims 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 generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. 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). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antigen-binding molecules presently claimed.
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 claimed genus of antibodies nor guidance as to which of the myriad of molecules encompassed by the claimed antibodies would meet the limitations of 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 antibodies encompassed by the claimed invention.
This rationale applies to aptamers as well because they are short, single-stranded DNA or RNA molecules (oligonucleotides) that fold into unique 3D structures to bind specific target molecules—such as proteins, peptides, and small molecules—with high affinity and specificity. They are often called "chemical antibodies." See 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).
The skilled artisan cannot envision the detailed chemical structure of the genus of claimed reagents for quantification of the claimed biomarkers, the internal control and the standards, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). 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.
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.
Claim(s) 17-18, 22-25 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Gill (US 20130085079).
The current claims direct to kit having reagents for analyzing two or more of the recited biomarkers, and together with computer storage and program for calculating the results from the detection of the biomarkers. Note, claim 17-18, 22-23, although depending on claim 2, nevertheless these claims direct to PRODUCT, and therefore are considered together with claim 24-25.
As to claim 22-23 and 24-25, Gill teaches using kits for detecting renin, neuropilin (NRP1) and thrombospondin 2 (TSP2) in biological samples from a subject (see Abstract and Table 1). Gill teaches using conventional immunological methods, e.g. antibodies of ELISA, for detection (section 0129, 0153, 0162, 0171).
As to claim 17-18 direct to computer storage and program for calculating test results, Gill also discloses using conventional computer program and storage for calculating/analyzing/storing data of immunological assays (section 0044-0046, 0209-0216).
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.
Claim(s) 17-18, 22, 24 are rejected under 35 U.S.C. 103 as being unpatentable over Hatanaka (Cancer Research 2006 Vol. 66, page 658, Abstract Only) in view of Gill.
Hatanaka teaches measuring TSP2 and NRP1 gene expression for diagnosing esophageal cancer.
However Hatanaka does not explicitly teach placing the reagents in a kit for analysis. Nevertheless using kit is considered common and routine in the field such as aforementioned Gill teaches using kits for the assays (Abstract; section 0016-0017).
Therefore, 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 place all the necessary reagents in a kit as taught by Gill for convenience and ensuring reproducibility of assay.
As to claim 17-18 direct to computer storage and program for calculating test results, Gill also discloses using conventional computer program and storage for calculating immunological assays (section 0044-0046, 0209-0216).
Conclusion
No claim is allowed.
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CHANGHWA J. CHEU
Primary Examiner
Art Unit 1678
/CHANGHWA J CHEU/Primary Examiner, Art Unit 1678