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 1-27 are pending and have been considered on the merits herein.
Specification
The disclosure is objected to because of the following informalities: at multiple instances, the specification refers to the AABC3 gene (0036, 0039, 0059, 0062, 0104) which is not a known gene or appear to be the correct gene regarding applicants’ invention. Applicants’ specification (0108) refers to the ABCC3 gene transporter efflux, which appears to be the correct gene. Appropriate correction is required.
Claim Objections
Claims 2, 4, 22, 25 are objected to because of the following informalities: as stated above, the gene AABC3 is not a known gene or appear to be the correct gene regarding applicants’ invention. Applicants’ specification (0108) refers to the ABCC3 gene transporter efflux, which appears to be the correct gene. Appropriate correction is required.
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 2, 5-7, 16, 24, 26, 27 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.
While claim 2 includes the language “and/or” regarding the “measuring of gene, genetic or enzymatic activity” and thus the claim as currently written does not require measuring of blood flow, it is not clear how the measuring of gene, genetic or enzymatic activity is achieved by measuring blood flow.
Claims 5 and 24 recite the limitation "wherein measuring blood flow of the patient…" in claims 1 and 21, respectively. There is insufficient antecedent basis for this limitation in the claim. (The measuring of blood flow is found in claims 2 and 22).
Claims 6 and 27 recite the limitation "wherein measuring SLC22A9 transport activity from the hair" in claims 1 and 21, respectively. There is insufficient antecedent basis for this limitation in the claim. (The measuring of SCL22A9 activity (in a hair cell) is found in claims 2 and 22).
Claims 7 and 26 recite the limitation "wherein when the gene…related to SULT1A1" in claims 1 and 21. There is insufficient antecedent basis for this limitation in the claim. (The recitation of SULT1A1 is found in claims 2 and 22).
Claim 16 recites the limitation "wherein measuring sulfotransferase activity in the sample…" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) predicting a response to minoxidil comprising measuring gene, genetic and/or enzymatic activity in a sample of a patient to generate a value indicative of a biochemical activation response to minoxidil, comparing the activity value to a standardized value and predicting a response to minoxidil treatment based on said comparison. The claimed invention is directed to a naturally occurring correlation between the gene, genetic and/or enzymatic activity and a predicted response to minoxidil, i.e. a law of nature or natural phenomenon with an abstract idea which are themselves the judicial exception. The correlation is based upon gene, genetic and/or enzymatic activity occurring in the sample and therefore includes a natural principle which exists in principle apart from any human action and thus simply describes a relation set forth by a natural law and a response. In addition, the step of comparing, predicting, estimating and prescribing are also mental steps, which can be performed by a human using mental steps or critical thinking, which are themselves abstract ideas and are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception (Step 2A: YES), which may be termed a law of nature, an abstract idea, or both.
This judicial exception is not integrated into a practical application because the claims do nothing more than inform the audience of the law of nature and does not require any particular application other than to “apply it”. The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it." The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because steps of comparing, predicting and estimating a response does not require any particular application other than “apply it” to the judicial exception. Mere instruction to apply an exception cannot provide an inventive concept. Measuring gene, genetic and/or enzymatic activity in a sample from a patient is routine and conventional in art. As claimed, one merely compares measured values to a standardized value and measuring gene, genetic and/or enzymatic activity in the sample merely instructs scientists to use a well-known technique at a high level of generality and therefore there is no meaningful limitation which is unconventional to measuring gene, genetic and/or enzymatic activity. The steps of comparing values, predicting and estimating activity in a sample and predicting based upon said value does nothing more than instruct to “apply the natural law”. In order to integrate the exception into a practical application, one must add additional elements in which the judicial exception
Next, one must evaluate whether the claims as a whole integrate the judicial exception into a practical application, thereby imposing a meaningful limit on the judicial exception. Thus, one must identify whether there are any additional elements recited in the claim beyond the judicial exception. The Supreme Court’s decisions make it clear that judicial exceptions need not be old or long-prevalent, and that even newly discovered or novel judicial exceptions are still exceptions. For example, the mathematical formula in Flook, the laws of nature in Mayo, and the isolated DNA in Myriad were all novel or newly discovered, but nonetheless were considered by the Supreme Court to be judicial exceptions because they were "‘basic tools of scientific and technological work’ that lie beyond the domain of patent protection." Myriad, 569 U.S. 576, 589, 106 USPQ2d at 1976, 1978 (noting that Myriad discovered the BRCA1 and BRCA1 genes and quoting Mayo, 566 U.S. 71, 101 USPQ2d at 1965); Flook, 437 U.S. at 591-92, 198 USPQ2d at 198 ("the novelty of the mathematical algorithm is not a determining factor at all"); Mayo, 566 U.S. 73-74, 78, 101 USPQ2d 1966, 1968 (noting that the claims embody the researcher's discoveries of laws of nature). The Supreme Court’s cited rationale for considering even "just discovered" judicial exceptions as exceptions stems from the concern that "without this exception, there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’" Myriad, 569 U.S. at 589, 106 USPQ2d at 1978-79 (quoting Mayo, 566 U.S. at 86, 101 USPQ2d at 1971). See also Myriad, 569 U.S. at 591, 106 USPQ2d at 1979 ("Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the 101 inquiry.").
Measuring gene, genetic and/or enzymatic activity in a sample is routine and conventional in art. Further, the correlation, i.e. law of nature because it is the consequence of a natural process of the body, and the predicting a response is a mere mental step. In order to integrate the exception into a practical application. In this case, the claims to do not integrate the exception because it does not rely on, use or act on the judicial exception, i.e. the claim does not do anything after arriving at the relevant information, for example a treatment step. It is noted that claim 21 includes a “prescribing” step; however, this is a mental step and thus there is not practical application beyond the judicial exception.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 1-27 is/are determined to be directed to a judicial exception.
For these reasons the claims are rejected under section 101 as being directed tonon-statutory subject matter.
Claim Rejections - 35 USC § 102
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.
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) 1, 2, 8, 10-15, 17-22 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by each of EP2761017B1 (IDS) and US8691518B2 (the teachings of US’518 are the same as EP017) to Tam et al.
Regarding claims 1, 2, 21, 22, EP017 teaches a method for predicting minoxidil response for the treatment of androgenetic alopecia comprising obtaining a sample from a subject of one or more hair follicles or a scalp biopsy, performing an assay to measure minoxidil sulfotransferase (SULT1A1 enzymatic) activity in the sample, and generating an activity value and comparing the value to a standardized value representing high or low expected minoxidil response in the subject (0009, 0018, 0029).
Regarding claim 8, the minoxidil treatment is for androgenetic alopecia (0007, 0009).
Regarding claim 10, the response to treatment is increased or improved hair growth or retention (0009).
Regarding claims 11 and 12, the standardized activity value pertains to a biochemical response based on minoxidil dosage and is associated with hair growth or retention for a class of individuals (0009) and regarding claim 13 is compared to a database to generate the likelihood that the patient will respond to minoxidil. The database is continuously updated to provide statistical adaptation based on past treatments and response thereto (0028, 0029).
Regarding claim 14, the method involves obtaining a sample of one or more hair follicles or a scalp biopsy and measuring sulfotransferase activity (0009, 0020).
Regarding claim 15, the measuring of activity in the sample occurs before being administered a minoxidil treatment and is compared to measured activities in a database from patients’ past treatments and response thereto (0029).
Regarding claims 17, 18, 20, the measuring of activity is performed via a colorimetric assay device and the method comprises placing and mixing a hair follicle in a reaction mixture containing potassium phosphate buffer, magnesium chloride, PAP or PAPS, p-nitrophenyl sulfate and minoxidil for a length of time and then stopping the reaction (0010, 0021-0025).
Regarding claim 19, the predicting of a minoxidil response uses a neural network (0030).
Regarding claim 21, the method and results from the colorimetric assay allows one to determine the optimal treatment including minoxidil dosage and frequency (0027, 0028, 0030).
Thus, the reference anticipates the claimed subject matter.
Claim(s) 1, 2, 8, 10-15, 17-22 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Goren et al. (US20140220609A1).
Regarding claims 1, 2, 21, 22, Goren teaches a method for predicting minoxidil response for the treatment of androgenetic alopecia comprising obtaining a sample from a subject of one or more hair follicles or a scalp biopsy, performing an assay to measure minoxidil sulfotransferase (SULT1A1 enzymatic) activity in the sample, and generating an activity value and comparing the value to a standardized value representing high or low expected minoxidil response in the subject (abstract, 0009-0011, 0021-0023).
Regarding claim 8, the minoxidil treatment is for androgenetic alopecia (0009, for example).
Regarding claim 10, the response to treatment is increased or improved hair growth or retention (0010, 0030).
Regarding claims 11 and 12, the standardized activity value pertains to a biochemical response based on minoxidil dosage and is associated with hair growth or retention for a class of individuals (0010) and regarding claim 13 is compared to a database to generate the likelihood that the patient will respond to minoxidil. The database is continuously updated to provide statistical adaptation based on past treatments and response thereto (0033).
Regarding claim 14, the method involves obtaining a sample of one or more hair follicles and measuring sulfotransferase activity (0010, 0024, 0038, 0040).
Regarding claim 15, the measuring of activity in the sample occurs before being administered a minoxidil treatment and is compared to measured activities in a database from patients’ past treatments and response thereto (0033).
Regarding claims 17, 18, 20, the measuring of activity is performed via a colorimetric assay device and the method comprises placing and mixing a hair follicle in a reaction mixture containing potassium phosphate buffer, magnesium chloride, PAP or PAPS, p-nitrophenyl sulfate and minoxidil for a length of time and then stopping the reaction (0025, 0028, 0029).
Regarding claim 19, the predicting of a minoxidil response uses a neural network (0034).
Regarding claim 21, the method and results from the colorimetric assay allows one to determine the optimal treatment including minoxidil dosage and frequency (0031).
Thus, the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 3, 9, 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over each of EP2761017B1 (IDS) and US8691518B2 (the teachings of US’518 are the same as EP017) to Tam et al., and Goren et al. (US20140220609A1) as applied to claims 1, 2, 8, 10-15, 17-22 above, and further in view of Ramos (JEADV, 2021, IDS) and Ramos (JEADV, 2020, IDS).
The teachings of each of EP2761017B1 (IDS) and US8691518B2 to Tam et al., and Goren et al. (US20140220609A1) are found above.
Regarding claim 9, while the references do not teach generating plural activity values and comparing to plural standardized activity values, it would be will within the purview of one of ordinary skill in the art to test multiple samples from an individual. The references teach comparing to a dynamic database which is continuously updated for statistical adaptation based on treatments and responses thereto so the database can adapt to a patient pool. Therefore, it would be obvious to generate plural activities to compare to the changing treatments and responses in the database/standardized activities therein.
The references do not teach oral minoxidil.
Ramos (JEADV, 2021) teaches a method of predicting response to oral minoxidil comprising measuring minoxidil sulfotransferase (SULT1A1) activity in sample from female pattern hair loss subjects. Ramos teaches that a lower follicular SULT1A1 activity threshold is required for bioactivation of oral minoxidil compared to topical minoxidil, due to extensive metabolization of oral minoxidil by liver SULT1A1. 3rd and 4th para.).
Ramos (JEADV, 2020) teaches a method of predicting response to oral minoxidil comprising measuring minoxidil sulfotransferase (SULT1A1) activity in hair follicle outer roof sheath cells (ORS). Ramos teaches that ORS express SULT1A1 and has been used to predict topical minoxidil response. Oral minoxidil is metabolized by the liver and thus Ramos seeks to determine if the liver or ORS sulfotransferases are responsible for oral minoxidil bio-activation and efficacy in treating female pattern hair loss. Hairs are assayed in a reaction mixture containing phosphate buffer, magnesium chloride, PAP, p-nitrophenyl sulfate and minoxidil (4th parag.). Values of less than 0.4 AU are validated markers of low follicular sulfotransferase activity. Ramos find that ORS bioactivation predicts clinical response in subjects (4th-6th parag.).
Thus, before the effective filing date of the claimed invention, it would have been obvious to a posita to measure gene, genetic and/or enzymatic activity, specifically SULT1A1 activity to predict a response to oral minoxidil in light of the teaching of the Ramos references which teach predicting a response to oral minoxidil comprising measuring minoxidil sulfotransferase (SULT1A1) activity. Thus, one would have had a reasonable expectation of successfully predicting a response to oral minoxidil when measuring gene, genetic and/or enzymatic activity when combining the methods of the prior art references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 8, 10, 11, 12, 13, 14, 15, 17, 18, 20, 21, 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 10, 12, 14, 22 of U.S. Patent No. 8691518 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to methods of predicting a response to minoxidil for the treatment of androgenetic alopecia comprising obtaining a sample from a subject of one or more hair follicles performing a colorimetric assay to measure minoxidil sulfotransferase (SULT1A1 enzymatic) activity in the sample, and generating an activity value and comparing the value to a standardized value representing high or low expected minoxidil response in the subject. The response to treatment is increased or improved hair growth or retention and the standardized activity value pertains to a biochemical response based on minoxidil dosage and is associated with hair growth or retention for a class of individuals. The values are compared to generate the likelihood that the patient will respond to minoxidil. The methods involve obtaining a sample of one or more hair follicles and measuring sulfotransferase activity before being administered a minoxidil treatment and is compared to measured activities from patients’ receiving a particular dose.
The measuring of activity is performed via a colorimetric assay device and the method comprises placing and mixing a hair follicle in a reaction mixture containing potassium phosphate buffer, magnesium chloride, PAP or PAPS, p-nitrophenyl sulfate and minoxidil for a length of time and then stopping the reaction.
The instant claims generically claim a sample, while the reference claims are drawn to hair sample; however, the examined claims would be anticipated by the reference patent claims.
Claims 1, 2, 8, 10, 11, 12, 13, 14, 15, 17, 18, 20, 21, 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 9, 13 of U.S. Patent No. 10633688. Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to methods of predicting a response to minoxidil for the treatment of androgenetic alopecia comprising obtaining a sample from a subject of one or more hair follicles performing a colorimetric assay to measure minoxidil sulfotransferase (SULT1A1 enzymatic) activity in the sample, and generating an activity value and comparing the value to a standardized value representing high or low expected minoxidil response in the subject. The response to treatment is increased or improved hair growth or retention and the standardized activity value pertains to a biochemical response based on minoxidil dosage and is associated with hair growth or retention for a class of individuals. The values are compared to generate the likelihood that the patient will respond to minoxidil. The methods involve obtaining a sample of one or more hair follicles and measuring sulfotransferase activity before being administered a minoxidil treatment and is compared to measured activities from patients’ receiving a particular dose.
The measuring of activity is performed via a colorimetric assay device and the method comprises placing and mixing a hair follicle in a reaction mixture containing potassium phosphate buffer, magnesium chloride, PAP or PAPS, p-nitrophenyl sulfate and minoxidil for a length of time and then stopping the reaction.
The instant claims generically claim a sample, while the reference claims are drawn to hair sample; however, the examined claims would be anticipated by the reference patent claims.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2017007921 for teaching a method for predicting if a subject (having androgenetic alopecia) will respond to minoxidil treatment comprising measuring blood flow of the subject both before and after minoxidil administration using Doppler velocimetry (0006-0008, 0019) and testing for SULT1A1 activity (0068, Ex. 2, 0076-0080).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651