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 .
Priority
This application filed 11/09/2021 is a Continuation of PCT/CN2021/085090, filed 04/01/2021, and claims foreign priority to 202011404354.4, filed 12/04/2020. The claims are therefore examined as filed on 12/04/2020, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 1-8 are pending.
Claims 1-2 and 5-6 are objected to.
Claims 1-8 are examined.
Claims 1-8 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pg 8-11 of the Specification). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1-2, and 5-6 are objected to because of the following grammatical informalities:
Step (1) of claims 1 and 5 should read “splitting and filtering [[a]] sample data”
Step (2) of claim 1 should read “acquiring a sequencing data file of each HLA gene”
Step (1) of claims 2 and 6 should read “splitting and filtering [[a]] sample downlink data”
Step (8) of claims 2 and 6 should read “outputting the percentage and average percentage of each HLA gene, and the negative or positive judgement result to a report file”
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: the modules of claims 5-6, including the “splitting and filtering module”, “gene sequencing data file acquisition module”, “reference gene generation module”, “calculation module for a percentage in each HLA gene”, “calculation module for a percentage of a HLA gene chromosome region”, “calculation module for a total percentage of each chromosome of HLA gene”, “negative or positive judgment module”, and “report file generation module.”
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 5-8 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.
Claims 5 and 6 recite several modules, including a “splitting and filtering module”, “gene sequencing data file acquisition module”, “reference gene generation module”, “calculation module for a percentage in each HLA gene”, “calculation module for a percentage of a HLA gene chromosome region”, “calculation module for a total percentage of each chromosome of HLA gene”, “negative or positive judgment module”, and “report file generation module” for performing various functions. However there is no written disclosure of structure, material or acts for performing the recited functions. Therefore, the claims fail to comply with the written description requirement.
Claims 7-8 depend from claim 5 and do not resolve the above issue, therefore these claims also fail to comply with the written description requirement.
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, 4, and 5-8 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 2 and 6 are unclear with respect to the phrase “when 0.5%< HLA% < 3%, the failure of judgment is prompted, and the cell HLA chromosome may be in a deficiency phase after the recipient transplantation.” It is unclear what “failure of judgement is prompted” means in this case – the Examiner assumes that this means that HLA Loss cannot be determined because it does not fall within the positive or negative judgment criteria set earlier in the claim, but it is unclear based on the wording. Similarly, the phrase “the cell HLA chromosome may be in a deficiency phase after the recipient transplantation” is unclear because the concept of a "deficiency phase" for a chromosome after transplantation is not a standard term – the Examiner assumes this relates to the failure of a chromosome to correctly transplant to a recipient, but it is unclear how this would be a phase.
It is also unclear from the claims what should be done in the event that the judgement fails (when 0.5%< HLA% < 3%), as the following step (8) involves reporting a negative or positive judgement based on the HLA percentage. It is unclear if a positive or negative judgement is still assigned in this case, or if no judgement would be provided.
For clarity, the phrasing may be changed to “when 0.5%< HLA% < 3%, HLA loss is unable to be determined” and additional steps as to what happens when this occurs may be added.
Claims 4 and 7-8 depend from claims 2 and 6 respectively, and do not resolve the above issue, therefore these claims are also indefinite.
In claims 5-6, the limitations of the “splitting and filtering module”, “gene sequencing data file acquisition module”, “reference gene generation module”, “calculation module for a percentage in each HLA gene”, “calculation module for a percentage of a HLA gene chromosome region”, “calculation module for a total percentage of each chromosome of HLA gene”, “negative or positive judgment module”, and “report file generation module” invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. There is no disclosure of structure, material or acts for performing the recited function, and it is unclear if the modules in question relate to software, hardware, or other implementation. Therefore, the claim is also indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claims 7-8 depend from claim 5 and do not resolve the above issue, therefore these claims are also indefinite.
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 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental processes and mathematical concepts, without significantly more.
The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of matter?
(2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea?
(2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application?
(2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?
With regard to step (1) (Are the claims directed to a process, machine, manufacture or composition of matter?): Yes. The claims are directed to one of the statutory classes. Claims 1-4 are directed to a process (analysis method), and claims 5-8 are directed to a machine product (analysis processing apparatus).
With regard to step (2A)(1) (Do the claims recite a judicially recognized exception?): Yes. Claims 1-8 recite the abstract ideas of processing data using mental steps and mathematical concepts. Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see MPEP 2106.04).
Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to:
Splitting and filtering sample data to obtain a filtered sample sequence (mental process; the human mind is capable of splitting and filtering data; claims 1-2, 5)
Judging a negative or positive result of HLA Loss (mental process; the human mind is capable of judging a result based on data; claims 1-2, 5)
Aligning the filtered sample sequence to a reference gene sequence of each HLA gene, aligning the sequencing data file to the reference gene (mental process; the human mind is capable of aligning two sequences; claims 2, 6)
Performing statistics on respective sequencing depths of the recipient and the donor in a position SNP of each gene, and averaging a depth frequency of the recipient in all the SNP positions of each HLA gene to obtain the percentage occupied in each HLA gene (mental process/mathematical concept; the human mind is capable of performing statistics and calculating an average to obtain a percentage; performing statistics and calculating an average is a mathematical concept equivalent to performing a calculation; claims 2, 6)
Averaging the percentage of the recipient in each HLA gene (mental process/mathematical concept; the human mind is capable of calculating an average; calculating an average is a mathematical concept equivalent to performing a calculation; claims 2, 6)
Obtaining a total percentage (mental process/mathematical concept; the human mind is capable of calculating total percentage based on obtained percentage data, and calculating total percentage is equivalent to performing a calculation; claims 1-2, 5-6)
Dependent claims 3-4 and 7-8 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas.
Therefore, the claims recite elements that constitute one or more judicial exceptions.
With regard to step (2A)(2) (Do the claims recite additional elements that integrate the judicial exception into a practical application?): No. The claims recite the additional element of acquiring a sequencing data file of each HLA gene, acquiring the type of each HLA allele from a recipient and a donor before and after transplantation (to generate a reference gene), and outputting the percentage and average percentage of each HLA gene and negative or positive judgement result to a report file. Claims 5-8 also recite the additional element of “an analysis processing apparatus” with “modules” for performing each of the method steps.
While the claims recite the additional elements of acquiring and outputting data, such data gathering and outputting steps, without any technical details of how the data is obtained output in a way that integrates the judicial exception, is an insignificant extrasolution activity that does not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. Similarly, while claims 5-8 recite the additional element of an analysis apparatus (assumed to be a typical computer), they do not provide any specific details by which the apparatus performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of the computer are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited apparatus/computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a computer (see MPEP 2106.05(f)). Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea.
With regard to step (2B) (Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?): No. The claims recite an abstract idea with additional elements; however, these additional elements are general computer elements added to abstract ideas, and non-particular instructions to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). General computer elements used to perform an abstract idea do not provide an inventive concept, and similarly, non-particular instructions to gather output data do not provide an inventive concept. Non-particular instructions to gather or output data are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Receiving or transmitting data over a network” from Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362, “Storing and retrieving information in memory” from Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 are recognized as conventional activities). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept.
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 Rejection
Claims 1, 3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over JAN 2019 “Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation” in view of TYLER 2019 “Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient’s Chimerism Status” and WITTIG 2015 “Development of a high-resolution NGS-based HLA-typing and analysis pipeline.”
Claim Interpretation and Scope and Contents of Prior Art
Claims 1 and 5 recite an analysis method and analysis processing apparatus for HLA loss, wherein the analysis steps comprise splitting and filtering a sample data to obtain a filtered sample sequence, acquiring sequencing data file of each HLA gene, wherein the sequencing data file comprises the sample data of each HLA gene, generating a first allele sequence as a reference gene before recipient transplantation, acquiring a percentage occupied in each HLA gene after the recipient transplantation, acquiring a percentage of the HLA gene chromosome region after the recipient transplantation. denoted by HLA%, acquiring a total percentage of each chromosome in a cell after the recipient transplantation denoted by STR%, and judging a negative or positive result of HLA Loss after the recipient transplantation. With respect to these limitations, JAN teaches generating targeted sequencing data from patients before and after transplantation and comparing them (pg 2201), and determining variant allele frequency after transplantation at time of relapse (Fig 1-2) and also teaches determining loss of heterozygosity across chromosome 6 at time of relapse after transplantation (Fig 2). JAN also teaches chimerism analysis, which can provide percentage of the donor chromosome in a cell after transplantation, but does not specifically teach acquiring a total percentage of each chromosome in a cell after the recipient transplantation denoted by STR%. However, TYLER teaches performing an STR chimerism assay and calculating post-transplantation percent donor or percent recipient as the mean of five informative markers (Abstract, pg 484 col 2). JAN also does not specifically teach splitting and filtering the sample sequencing data before analysis; however WITTIG 2015 teaches splitting and filtering sequencing data for HLA typing by reducing the number of mappings to single start point mappings (pg 3 col 1 par 2) and filtering to reduce the number of possible alleles and so the alleles have full coverage and a specific central read coverage (pg 3 col 2).
Claims 3 recites the limitation of claim 1 wherein each HLA gene is respectively HLA-A, HLA-B, HLA-C, HLA-DRB I, HLA-DQB 1, and HLA-DPB 1. With respect to this limitation, JAN teaches that the analyzed HLA genes include HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, and -DRB3 (pg 2022 col 1 par 3).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in HLA loss analysis would have been motivated to combine the teachings of JAN with the methods of TYLER and WITTIG, in order to achieve the claimed invention, because performing an STR chimerism assay to determine chromosome amount after transplantation can be used to predict a risk of relapse, and because the STR method is a known method of determining this with good accuracy and reproducibility (TYLER pg 483 col 1), and because splitting and filtering sequencing data reduces the number of possible alleles and results in a greater likelihood of determining the correct genotype by reducing possible errors (WITTEG pg 3 col 2). A person of ordinary skill would reasonably expect success from combining these teachings, as JAN,TYLER, and WITTIG all teach methods of HYLA loss analysis using sequencing data. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claims Without an Art Rejection
No art rejection is applied to claims 2, 4, and 6-8. JAN in view of TYLER and WITTIG, cited above, while teaching the broader steps of claims 1 and 5, do not teach the specific steps of the analysis in claims 2 and 6, such as averaging a depth frequency of the recipient in all the SNP positions of each HLA gene, and judging a negative or positive result of HLA loss wherein HLA%<0.5% and STR%>3%HLA Loss is judged positive and HLA %>3%, HLA Loss is judged negative. No additional combinable art before the effective filing date could be found to render these claims as obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R. Skowronek can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.C.L./
Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687