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 .
This action is in response to the papers filed November 26, 2025. Currently, claims 11-22 are pending. Claims 15-16, 20-21 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of HLA-B*51:02, Claims 11-14, 17-19, 22 in the paper filed November 26, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/CN2021/112752 filed August 16, 2021 and claims priority to Australia 2020902931, filed August 18, 2020.
The priority application does not disclose the HLA-B*51:02 allele. Therefore, the claims enjoy the priority of August 16, 2021.
Drawings
The drawings are acceptable.
Improper Markush Rejection
Claims 11-14, 17-19, 22 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
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-B alleles, namely 13:01 or 51:01 or 51:02.
The recited alternative species in the groups set forth here do not share a single structural similarity, as each different allele that could be detected is itself located in a separate region of the genome and has its own structure. The alleles recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequences. 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 drug hypersensitivity reaction. Accordingly, while the different alleles are asserted to have the property of being associated with drug hypersensitivity reaction, 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 genes 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 genes 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 associated with drug hypersensitivity reaction.
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 associated with drug hypersensitivity reaction.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 11-14, 17-19, 22 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 11 is directed to “a method for evaluating the risk developing a drug hypersensitivity reaction caused by an anti-epileptic drug with a sulfonaminde derivative and treating the hypersensitivity reaction”.
Claim 12 is directed to “a method for treating the hypersensitivity reaction caused by the anti-epileptic drug”.
Claim 11 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “identifying the subject as having the drug hypersensitivity at increased risk of developing drug hypersensitivity”) and a law of nature/natural phenomenon (i.e. the natural correlation between the HLA-B 51:02 allele and drug hypersensitivity reaction).
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, claims 11 and 12 involve the patent-ineligible concept of an abstract process. The claims require performing the step of “identifying the subject as having the drug hypersensitivity at increased risk of developing drug hypersensitivity”. Neither the specification nor the claims set forth a limiting definition for "identifying" and the claims do not set forth how “identifying” is accomplished. As broadly recited the identifying step may be accomplished mentally by thinking about a subject’s HLA-B state and assessing whether the subject has drug hypersensitivity at increased risk of developing drug hypersensitivity. Thus, the determining step constitutes an abstract process idea.
A correlation that preexists in the human is an unpatentable phenomenon. The association between the HLA-B 51:02 allele and drug hypersensitivity reaction is a law of nature/natural phenomenon. The "identifying" step and the preamble which tells users of the process to predict endometrial cancer in the sample, amounts to no more than an "instruction to apply the natural law". This identifying 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 "identifying" step does not require the process user to do anything in light of the correlation. The "identifying" 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 obtaining a sample, detecting the presence of HLA-B*51:02 and treating with a drug to treat the hypersensitivity reaction or an antiepileptic drug without a sulfonamide derivative, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. The administration step of any drug to treat hypersensitivity reaction is not particular to the judicial exception. The instruction to administer any drug that may treat the drug hypersensitivity reaction is general in nature. Thus, the claim is “directed to” the exception.
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. The obtaining a sample and detecting the presence of HLA-B*51:02 is 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 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 detecting the HLA-B*51:02 allele was well known in the art at the time the invention was made. The prior art teaches detecting HLA-B alleles. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any allele detection method to detect the allele. 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.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known.
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.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation 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.
Claims 11-14, 17-19, 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for evaluating the risk of developing a SCAR drug hypersensitivity reaction caused by zonisamide does not reasonably provide enablement for evaluating the risk of any drug hypersensitivity reaction caused by any anti-epileptic drug with sulfonamide derivative. 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.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims
The claims are drawn to a method for evaluating the risk of developing a drug hypersensitivity reaction caused by any anti-epileptic drug with a sulfonamide derivative by detecting the presence of HLA-B*51:02.
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The unpredictability of the art and the state of the prior art
The art teaches different drugs are influenced by different alleles in different drug hypersensitivity reactions. For example, Fan et al. (J. of Immunology Research, Vol. 2017, Article ID 3186328) teaches HLA association with drug-induced adverse reactions are associated with different alleles and different drugs. Fan illustrates in Table 1 drug induced ADRs and HLA allele associations. As illustrated in Table 1, the A*31:01 allele is associated with HSS and Lamotrigine where B*15:02 is associated with SJS/TEN for Lamotrigine. Further, different drugs are associated with different alleles. Each allele is associated with different drugs and different phenotypes.
Guidance in the Specification.
The specification provides no evidence that the broad scope of the claims is enabled. The specification, Table 2, provides 7 subjects have either the 51:01 or 51:02 allele. The specification does not provide how many of the subjects had the 51:02 allele and how many had the 51:01 allele. If only one of the 7 subjects had 51:02 allele, the percentage in the normal population and the diseased population would be the same. There would be no association between the allele and the drug hypersensitivity reaction. The specification is further only directed to zonisamide. The specification does not consider different anti-epileptic drugs.
The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to practice the claimed invention as a whole. The specification has not clearly provided a relationship between HLA-B*51:02 and risk of developing any drug hypersensitivity reaction to any anti-epileptic drug. The art demonstrates that different alleles are associated with different drug hypersensitivities and any anti-epileptic drugs. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of a working example and the negative teachings in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Claim Rejections - 35 USC § 112- Second 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.
Claims 12, 18-19, 22 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 pre-AIA the applicant regards as the invention.
A) Claims 12, 18-19, 22 are rejected over the recitation “the drug hypersensitivity reaction” in the preamble of Claim 12. Claim 12 does not refer to a drug hypersensitivity reaction. The claim was amended to remove the recitation. Thus, the claim lacks proper antecedent basis.
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.
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 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.
Claim(s) 11, 13, 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hu et al. (Seizure, Vol. 20, pages 431-432, 2011).
Hu teaches phenytoin-induced Stevens-Johnson syndrome with negative HLA-B*15:02 allele in mainland China patients. Hu teaches phenytoin (PHT) induced SJS was found in a patient with a HLA-B*5102 allele. Hu teaches carbamazepine (CX and phenytoin (PHT) are among the most common causes of antiepileptic drugs (AEDs)-induced cutaneous adverse reactions (page 431, col. 1). Hu teaches a woman was diagnosed as PHT-induced SJS and genetic testing was performed by PCR -SBT. HLA high resolution genotyping showed a heterozygous HLA-B*5102/HLA-B*4601 allele. The patient was administered steroids and antihistamine for 13 days and greatly improved.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12, 18, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (Seizure, Vol. 20, pages 431-432, 2011).
Hu teaches phenytoin-induced Stevens-Johnson syndrome with negative HLA-B*15:02 allele in mainland China patients. Hu teaches phenytoin (PHT) induced SJS was found in a patient with a HLA-B*5102 allele. Hu teaches carbamazepine (CX and phenytoin (PHT) are among the most common causes of antiepileptic drugs (AEDs)-induced cutaneous adverse reactions (page 431, col. 1). Hu teaches a woman was diagnosed as PHT-induced SJS and genetic testing was performed by PCR -SBT. HLA high resolution genotyping showed a heterozygous HLA-B*5102/HLA-B*4601 allele. The patient was administered steroids and antihistamine for 13 days and greatly improved.
Hu does not teach modifying or administering an antiepileptic drug that is not a sulfonamide derivative.
However, the ordinary artisan would have been motivated to have administered a different antiepileptic drug to the patient with adverse reactions to overcome the adverse reactions and to continue to treat the epilepsy. The ordinary artisan would have been motivated to have selected another well-known antiepileptic drug.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chung et al. (WO 2021/030925, February 25, 2021) teaches assessing risk of cutaneous adverse drug reactions cause by epidermal growth factor receptor inhibitor using HLA-B*51:02 allele. Chung does not teach hypersensitivity to drugs caused by sulfonamide derivative based antiepileptic drug.
Huyen et al. (J. Med Sci. Vol. 8(B) pages 395-400, Jun 10, 2020) teaches HAL-B*58:02 was found in patients administered traditional medicine who developed adverse drug reactions.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
January 22, 2026