DETAILED CORRESPONDENCE
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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 5, 2026 has been entered.
This action is in response to the papers filed February 5, 2026. Currently, claims 13-15, 18-20, 22-32 are pending. Claims 22-23, 25, 29, 32 have been withdrawn as directed to non-elected subject matter. All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election without traverse of HLA-B*3802 and Sulfasalazine, claims 13-21 in the paper filed May 5, 2025 is acknowledged.
Claims 22-23 have been withdrawn as directed to non-elected subject matter.
In view of the arguments with respect to phenotypes, the Examiner has rejoined SJS and TEN. Thus, SJS and TEN have been examined.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Improper Markush Rejection
Claims 13-15, 18-20, 25, 29 are rejected under the judicially approved “improper Markush grouping” doctrine. (See Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, page 7166). This rejection is appropriate when the claim contains an improper grouping of alternatively useable species. See In re Harnisch,631 F.2d 716, 719-20 (CCPA 1980). A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
Here each species is considered to each of the HLA alleles or combinations of HLA alleles.
The recited alternative species in the groups set forth here do not share a single structural similarity, as each different gene that could be detected is itself located in a separate region of the genome and has its own structure. The alleles, do not share a single structural similarity since each consists of a different nucleotide sequences with different drug responses. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with severe cutaneous adverse drug reactions. Accordingly, while the different alleles are asserted to have the property of being correlated with severe cutaneous adverse drug reactions, they do not share a single structural similarity.
MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited alleles do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the alleles will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited alleles would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being correlated with severe cutaneous adverse drug reactions.
MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they all have a sugar phosphate backbone. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to the asserted common use of being correlated with severe cutaneous adverse drug reactions.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
Response to Arguments
The response traverses the rejection. The response asserts each of the elements of the alternative claim language are HLA genes which belong to MHC Class I. The response argues the class of genes are HLA-B gene that are all located on the short arm of chromosome 6 and encode the alpha chain. This argument has been reviewed but is not persuasive. Not all members of the class, namely HLA-B genes will behave in the same way in the context of the claimed invention and each member can not be substituted one for the other with the expectation that the same intended result would be achieved. Applicant submitted “Updates in the pathogenies of SJS/TEN” by Justice to support their position, however the evidence provided in Table 1 demonstrates that not all HLA-B genes are similarly associated with the same toxicity. For example, HLA-B*15:02 is associated with carbamazepine, oxcarbazepine and phenytoin where, HLA-B*58:01 is associated with allopurinol and HLA-B*38 is associated with sulfamethoxazole.
The claim language also demonstrates not all of the alleles will not all behave in the same way as they are each associated with different SCAR reactions. Each of the HLA alleles are associated with subjects at risk of developing different reactions, namely SJS, TEN, DRESS. Not all members of the class will behave in the same way and thus, HLA-B alleles is not a proper art recognized class. Thus, there is no proper Markush. Thus, for the reasons above and those already of record, the rejection is maintained.
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 13-15, 25, 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 13 is directed to “a method for treating a SCAR induced by sulfasalazine” by “obtaining a sample”, “detecting” the allele, “identifying the subject as having SCAR” based upon the alleles and treating the SCAR induced by sulfasalazine.
Claim 18 is similarly directed to reducing the incidence of SCAR induced by sulfasalazine and administering a disease-modifying anti-rheumatic drug other than sulfasalazine. Newly added Claim 32 is also directed to treating SCAR induced by sulfasalazine by “obtaining a sample”, “detecting” the allele, “identifying the subject as having SCAR” based upon the alleles and treating the SCAR induced by sulfasalazine.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “detecting”, “identifying the subject as having SCAR based upon the alleles present”) and a law of nature/natural phenomenon (i.e. the natural correlation between the HLA-B*3802 allele and SCAR that is SJS or TEN).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 13 involves the patent-ineligible concept of an abstract process. Claim 13 requires performing the step of “detecting the HLA-B*3802 allele”. Neither the specification nor the claims set forth a limiting definition for " detecting the HLA-B*3802 allele " and the claims do not set forth how “detecting” is accomplished. As broadly recited the detecting step may be accomplished mentally by thinking about a subject’s allele and assessing risk of developing the severe cutaneous adverse reaction. Thus, the determining step constitutes an abstract process idea. The “identifying the subject” based on the alleles present is also a mental process.
A correlation that preexists in the human is an unpatentable phenomenon. The natural correlation between the HLA-B*3802 allele and SCAR that is SJS or TEN is a law of nature/natural phenomenon. The step (b) which tells users of the process to predict risk of developing severe cutaneous adverse drug reactions, amounts to no more than an "instruction to apply the natural law". This step is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The step does not require the process user to do anything in light of the correlation. The step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites administering a drug to treat the severe cutaneous adverse drug reaction, this is not an integration of the exception into a practical application. Instead, the claim requires a generic treatment for any drug to treat the severe cutaneous adverse drug reaction that is a liquid, steroid, immunoglobulin, or plasma replacement. There are no meaningful constrains on the administering step such that the particular treatment or prophylaxis consideration would apply because it is not limited to any particular manner or type of treatment. The limitation is at most an instruction to “apply” the judicial exception.
Furthermore, the claims are directed to administering the treatment to all of the patients. The claims do not require administering the treatment only to patients with the SCAR. The claim is conditional that the subject is identified only “if” HLA-B*38:02 allele is present, however the claim requires administer a drug regardless of “if” the allele is present. The claim does not specify which patients are treated or only treat a specific patient population based upon their genetic composition. The treatment is administered regardless of disease status; thus, this is not an integration of the judicial exception.
Accordingly, the claims are directed to judicial exceptions.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. If the detecting step is required to read on a genotyping step, the step is a mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the HLA allele of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining the HLA status of HLA-B*3802 was well known in the art at the time the invention was made. The claim merely instructs a scientist to use any analysis to determine the allele status. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claims are directed to patentable subject matter because they are directed to treating a SCAR induced by sulfasalazine by administering a drug that is a liquid, steroid, immunoglobulin, or plasma replacement. The response argues this is a particular treatment for a subject having sulfasalazine-induced SCAR. This argument has been considered but is not convincing because the mere recitation of “a drug” is not a particular treatment. As provided in MPEP 2106.04(d)(2), a particular treatment or prophylaxis is required. The MPEP states that the treatment must be “particular” i.e., specifically identified so that it does not encompass all applications of the judicial exception. Here, administration of “a liquid drug” or “a steroid drug”, for example, is not a particular treatment. Essentially, the claim is directed to “treat it” once a subject is identified as having SCAR. As illustrated in Example 49 of the 101 Guidelines, a general administration step is not sufficient. Thus, for the reasons above and those already of record, the rejection is maintained.
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.
Claims 13-15, 18-20, 25, 29, 32 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.
Claims 13-15, 25 are directed to identifying the subject as having SCAR or a risk of developing SCAR “if” HLA-B*3802 allele is step (b) is present. The claim does not require that the subject has the HLA-B*3802 allele. The claim requires administering a drug regardless. Thus, it is unclear whether patients without the HLA-B*3802 allele are also treated with the drug or whether the claim is intended to require HLA-B*3802 allele is present prior to administering a drug.
Claim 18 is directed to administering the disease modifying anti-rheumatic drug to the subject having SCAR. The claim lacks proper antecedent basis for “the subject having the SCAR” because the claim does not require a subject has SCAR. The claim requires identifying the subject only “if” HLA-B*3802 allele is present.
Claim 32 is idefinite because the claim lacks proper antecedent basis. The claim recites “the SCAR induced by sulfasalazine”. The claim does not require any subject has SCAR the claim only requires identifying the subject as having SCAR “if” HLA-B*3802 allele is present. The claim does not require the subject has SCAR.
Conclusion
No claims allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.A) Wang et al. (American Academy of Allergy, Asthma & Immunology, April 2021, Vol. 147, No. 4) teaches association of HLA-B alleles with phenotypes of co-trimoxazole-induced severe cutaneous adverse reactions including HLA-B*3802 (Table IV).
Chen et al. (NZ572259. March 30, 2012) teaches HLA alleles associated with adverse drug reactions. Chen teaches detecting HLA-B 3802 in subjects. Table 2 illustrates SJS patients with CBZ induced cutaneious ADRS. Chen teaches HLA-B*1502 is associated with an increased risk for an adverse drug reaction when the drug is carbamazepine.
Hallberg et al. (Lancet Diabetes Endrocrinol. Vol. 4, NO. 6, pages 507-516, June 2016) teaches two genome-wide association studies were published describing a strong association between agranulocytosis induced by antithyroid drugs and HLA-B*38:02. Agranulocytosis is a severe reduction in neutrophils causing profound immunosuppression. This is not considered a cutaneous adverse drug reaction since the skin is not involved.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
February 25, 2026