DETAILED ACTION
This application is being examined under AIA first-to-file provisions.
Status of claims
Canceled:
2, 5-7, 10, 13-15, 17, 21, 23, 25-27, 29, 31, 41
Pending:
1, 3-4, 8-9, 11-12, 16, 18-20, 22, 24, 28, 30, 32-40 and 42-47
Withdrawn:
18, 28, 35-40, 42-43 and 45
Examined:
1, 3-4, 8-9, 11-12, 16, 19-20, 22, 24, 30, 32-34, 44 and 46-47
Independent:
1 and 46
Allowable:
none
Rejections applied
Abbreviations
x
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
x
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
102, 103
JE
Judicial Exception
101 JE(s)
112/a
35 USC 112(a) and similarly for 112/b, etc.
101 Other
N:N
page:line
x
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed on the 12/14/2021 filing receipt, this application claims priority to as early as 2/19/2019. At this point in examination, all claims have been interpreted as being accorded this priority date.
Withdrawal / revision of objections and/or rejections
In view of the amendment and remarks:
The objections to the drawings are withdrawn.
The objections to the claims are withdrawn, however new objections are applied.
The 112/b rejections are withdrawn, except as noted below, however new rejections are applied.
The 102 rejection is withdrawn. Close art, for example as cited in the now withdrawn rejection as well as art cited on the IDSs and in the search histories, does not teach at least the recited "none of the one or more SNP(s) has a reference allele and alternate allele combination selected from the group consisting of A_G, G_A, C_T, and T_C." Applicant's 3/18/2026 remarks at p. 20 further support withdrawal of the rejection.
The previous 101 rejections are withdrawn. Referring to 101 analysis as organized in MPEP 2106, the 101 rejections are withdrawn at least in view of the analysis Step 2B relating to a non-conventional additional element causing the claim to read on significantly more than any recited JE (MPEP 2106.05(d)), the non-conventional additional element in this instance comprising at least the recited measuring an amount of a SNP-identified, recipient- or donor-specific nucleic acid in which no SNP has a reference allele and alternate allele combination selected from the group consisting of A_G, G_A, C_T, and T_C. In this regard, Applicant's 3/18/2026 remarks at p. 23 support withdrawal of the rejection.
Rejections and/or objections not maintained from previous office actions are withdrawn. The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
Claim objections
Claims 1, 3-4, 8-9, 11-12, 16, 19-20, 22, 24, 30, 32-34, 44 and 46-47 are objected to because of the following informalities. Appropriate correction is required. In each objection the claims are definite with respect to the issues cited here because interpretation would have been sufficiently clear to PHOSITA, but nonetheless the claims are objected to for consistency among the claims or as otherwise indicated. With regard to any suggested amendment below to overcome an objection, in the subsequent examination it is assumed that each amendment is made. However, equivalent amendments also would be acceptable. Any amendments in response to the following objections should be applied throughout the claims, as appropriate. For compact prosecution and examination, and planning for eventual allowance, the withdrawn claims also may be amended in order to keep them current with the rest of the claims.
The following issues are objected to:
Claim
Recitation
Comment
1,
44-46
A method...
in a hematopoietic stem cell transplant (HSCT) recipient...
(a)... the hematopoietic stem cell transplant (HSCT) recipient...
Once an abbreviation has been recited the first time anywhere in the claims, then just the abbreviation should be used consistently in every subsequent instance, without repeating the defining terms, throughout the claims. Here, the definition of "HSCT" is repeated inappropriately, in some instances twice in the same claim. This issue recurs, sometimes more than once, in each of the claims listed here. All of the claims should be reviewed throughout for this issue.
1, 8-9, 11, 18, 22, 24, 28, 34, 46
(b)...
wherein...
single nucleotide polymorphism(s) (SNP(s)
First, in claim 1, the parentheses are mismatched, apparently due to a previous error in designating the amendment.
Second, when writing, for example, "one or more widgets," it is not ordinary patent drafting practice and not ordinary English to write "one or more widget(s)." Instead, ordinary English is to write "one or more widgets." That is, the number of the noun agrees with the last preceding article or adjective, e.g. "more" agrees with "widgets" plural with no need to write "widget(s)." Similarly, any subsequent verb simply agrees with the last preceding subject, e.g. "one or more widgets are." Thus, the claim recitation quoted to the left here should recite "polymorphisms" and not "polymorphism(s)." Similarly, "SNP(s)" should instead read "SNPs." The claims should be reviewed in their entirety, and this issue should be corrected throughout.
Third, the claims presently are inconsistent with respect to the second issue above. Contrast claims 1 vs. 3. Claim 3 conforms with ordinary English grammar regarding "SNPs."
Fourth, as noted above, any subsequent verb should agree in number with the last preceding noun in a compound subject, e.g. in claim 22, "...SNPs comprise," not "...SNPs comprises..." The claims are inconsistent in this respect and should be reviewed in their entirety, and this issue should be corrected throughout and with respect to all subject-verb combinations as needed. Claim 24 is objected to similarly.
Fifth, the same issues regarding improper use of "(s)" and incorrect subject-verb agreement occur in the following instances and require correction, claim 8 ("population(s)"), claim 9 ("population(s) is") and claim 11 ("population(s)"). All claims should be reviewed for similar instances.
19
...acids or... acids is
Improper subject-verb agreement; should read "are"
20
...comprises
determining..., and
determining...
A colon should follow "comprises".
20, 32
...one or more ...specific nucleic acid by...
Should read "...specific nucleic acids"
32
...one or more polymorphic nucleic acid target.
Should read "...targets."
46
one or more processors
Should be indented
Claim rejections - 112/b
The following is a quotation of 35 USC 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 1, 3-4, 8-9, 11-12, 16, 19-20, 22, 24, 30, 32-34, 44 and 46-47 are rejected under 112/b, as indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate. For compact prosecution and examination, and planning for eventual allowance, the withdrawn claims also may be amended in order to keep them current with the rest of the claims. With regard to any suggested amendment below, for claim interpretation during the present examination it is assumed that each amendment suggested here is made. However equivalent amendments also would be acceptable.
The following issues cause the respective claims to be rejected under 112/b as indefinite:
Claim
Recitation
Comment (suggestions in bold)
1, 46
A method...
transplant status
In claim 1, the recited "transplant status" requires a preceding grammatical article, e.g. "a transplant status." Contrast claim 46.
Also, in claim 46 but not rendering that claim indefinite, "transplantation status" differs from "transplant status" in claim 1.
However, in claim 46, the later recited "the transplant status" in steps (c) and (d) requires but lacks antecedent.
1, 19, 46
(b)...
wherein...
the donor-specific nucleic acids
Requires but lacks clear antecedent at least because the recitation of "donor-specific nucleic acids" previously was instantiated as "one or more..." In claim 19, this issue occurs at both of "donor-specific" and "recipient-specific" (contrast claim 20).
1
(b)...
wherein...
wherein...
expected allele frequency
A grammatical article should precede "expected allele frequency," e.g. "an."
1, 46
(c) ...
(ii) ... a time interval post-translation...
(d) ...
ii) ... a time interval post-translation...
iii) ... a threshold post-translation
iv) ... a time interval post-translation.
In claim 1, the relationships are unclear between each instantiation listed here and similar instantiations in preceding steps. Possibly all such instantiations should be amended to include "first," "second," etc. Or, if intended to be the same, then the subsequent instantiations may be amended to "[[a]]the..."
Similar issues render claim 46 indefinite.
3, 19
the amount
In one instance in claim 3 and two instances in claim 19, "the amount..." requires but lacks antecedent and probably should read "an amount..."
3
the donor
Requires but lacks antecedent, noting that "donor" previously is only recited as an adjective. Only the noun form can provide antecedent.
19, 46
wherein...,
wherein...
wherein...
wherein...
The relationship is unclear between the "wherein" clauses at least for lack of a grammatical article, e.g. "or," "and," etc. before the last "wherein" clause. This rejection was not addressed and is maintained.
Similarly in claim 46, following step (b), the list of three "wherein" clauses requires a conjunction.
20
the total copy number
Requires but lacks antecedent
20, 44
...by multiplying the one or more recipient-specific or one or more donor-specific nucleic acid fraction and...
In claim 20, the recited "one or more" is inconsistent with the singular grammatical number of "fraction." Considering just this recitation, possibly "fractions" should be recited.
However, the recited "the one or more..." requires but lacks antecedent, there being no preceding instance of "fraction," singular or plural, in any of claims 20, 19 or 1.
The same issues occur in claim 44.
Also, in claim 44, "faction" should read "fraction."
Also, in claim 44, the verb "ranges" appears grammatically inconsistent with the recited "one or more..." regarding subject-verb agreement as to grammatical number.
32
the genotypes for at least one of the donor and the recipient is not known
First, requires but lacks clear antecedent.
Second, improper subject-verb agreement: "...genotypes... is..."
32
the transplantation determination
Requires but lacks antecedent
32
the one or more
nucleic acids from said HSCT recipient
Requires but lacks clear antecedent
32
...based on measurements of one or more
polymorphic nucleic acid target.
First, the recited "one or more... target" should read "one or more... targets" since the noun should agree with the last part of the "or" clause, i.e. the "more." This rejection is maintained.
34
the measured frequency of a reference allele of the one or more SNP(s) in the nucleic acids in the biological sample
Requires but lacks clear antecedent; possibly should read "a measured..."
34
the expected allele frequency of the reference allele in a reference population
Requires but lacks clear antecedent -- two instances.
Possibly should read "an expected..."
And, possibly should read "a reference allele..."
If the intended antecedents are in claim 1, step (b), 2nd "wherein" clause, then this is not clear.
34
the fixed cutoff
The recitation requires but lacks proper antecedent. Before the previous amendment, the previously recited "a fixed cutoff" would have provided antecedent, but that recitation is now amended to "a fixed cutoff algorithm," in which "fixed cutoff" now is an adjective, which does not provide proper antecedent.
44, 46
the post-transplantation sample from a recipient...
a recipient fraction in the post-transplantation sample...
In claim 44, the recited "the post-transplantation sample" requires but lacks clear antecedent (two instances).
Also, the relationship is unclear between this "sample" and the "sample" recited in claim 1, step (a).
Also, the relationship is unclear between this instantiation of "recipient" versus the claim 1, preamble "recipient." A similar issue occurs in claim 46 between the preamble and step (a) instantiations of "...recipient."
46
(b)...
wherein...
the donor-specific nucleic acids are...
Requires but lacks clear antecedent at least because "donor-specific nucleic acids" previously was instantiated as "one or more..."
46
(a)... after transplantation
First, a grammatical article is needed before the noun "transplantation," noting that the previous instance of "transplantation" in the preamble was an adjective. The same issue recurs in step (b).
Second, a semi-colon is needed at the end of step (a), before step (b).
Claim interpretations
The following claim interpretations apply to all instances of the following terms throughout all claims:
Claim
Recitation
Comment
33
a fixed cutoff algorithm
Definite under 112/b after properly invoking 112/f. Recites means (or an equivalent, nonce term, here "algorithm") and function and/or result (here "fix cutoff") without reciting steps or structure to prevent invoking. However, clearly linked portion of the specification do disclose sufficient structure, material, or acts and not just desired results, as exemplified at 4:31 through 5:2. MPEP 2181.III-IV pertain.
33
a dynamic clustering algorithm
Definite under 112/b after properly invoking 112/f. Recites means (or an equivalent, nonce term, here "algorithm") and function and/or result (here "dynamic clustering") without reciting steps or structure to prevent invoking. However, clearly linked portion of the specification do disclose sufficient structure, material, or acts and not just desired results, as exemplified at 5:13-19. MPEP 2181.III-IV pertain.
33
an individual polymorphic nucleic acid target threshold algorithm
Definite under 112/b after properly invoking 112/f. Recites means (or an equivalent, nonce term, here "algorithm") and function and/or result (here "individual polymorphic nucleic acid target threshold") without reciting steps or structure to prevent invoking. However, clearly linked portion of the specification do disclose sufficient structure, material, or acts and not just desired results, as exemplified at 5:20-26. MPEP 2181.III-IV pertain.
Claim rejections - 112/a
The following is a quotation of 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.
Regarding issues of written description support stemming even from the original claims and original disclosure, MPEP 2161.01.I (e.g. 6th para.), 2163.I and 2163.I.A pertain: "[O]riginal claims may lack written description when the claims define the invention in functional language specifying a desired result but the specification does not sufficiently describe how the function is performed or the result is achieved. For software, this can occur when the algorithm or steps/procedure for performing the computer function are not explained at all or are not explained in sufficient detail (simply restating the function recited in the claim is not necessarily sufficient). In other words, the algorithm or steps/procedure taken to perform the function must be described with sufficient detail so that one of ordinary skill in the art would understand how the inventor intended the function to be performed" (MPEP 2161.01.I,6th para.).
Response to arguments regarding Claim Rejections - 35 USC 112/a -- written description
Applicant states (original emphasis removed, bold emphasis added, applicant remarks: p. 19):
Applicant submits that the application provides sufficient written description of the amended claim 46. For example, the specification describes systems that can be used by a person of ordinary skill in the art to carry out any of the methods of the present application. See the application as published, paragraphs [00018], [0077]-[0087], [0121]-[0145], [0222]-[0228], [0338]-[0346], [0349]-[0378], and FIGs. 2-5, and 11. Furthermore, Applicant submits that a person of ordinary skill in the art would know how, based on the teachings of the specification, to carry out the method of claim 1 in a computer-implemented system with data handling steps carried out in software modules-which directly aligns with amended claim 46.
In a claim to a 101 machine or manufacture, in claim 46 a "system," the BRI reads not on the person of ordinary skill carrying out methods as stated by Applicant ("...systems that can be used by a person of ordinary skill in the art to carry out any of the methods of the present application") but instead reads on the person of ordinary skill making the "system," in this instance a "system" and "instructions" configured to themselves perform the recited steps of "obtaining" and "determining," implying automated, robotic performance of these physical steps. The claim is not clearly limited to a system configured to assist a person in performing the physical steps, and instead, as discussed in the rejection, the claim reads on embodiments in which the "system" itself is required to perform the physical steps. As discussed in the rejection, it remains unclear that there is support for PHOSITA to make such a "system" including the necessary hardware and software.
If there is not written description support for the "system" to itself perform the recited physical steps, then it may help to overcome the rejection to amend so that the "system" and "instructions" are clearly not required to perform those steps, and, for example, the recited "instructions" are limited to performing the data processing steps, e.g. after receiving data generated by "obtaining" and "determining" steps which are not themselves claimed.
Written description
Claim 46 is rejected under 112/a as failing to comply with the written description requirement. The claims read on subject matter which is not described in the specification in such a way as to reasonably convey to PHOSITA that the inventors, at the time the application was filed, had possession of the claimed invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted. With regard to any suggested amendment(s) below to overcome a rejection, equivalent amendments also would be acceptable.
Claim 46 recites "A system...:" "(a) obtaining..." and "(b) determining..."
In a BRI, each of the recited "obtaining..." and "determining..." read on embodiments in which the "obtaining..." and "determining..." require physical steps, e.g. wet laboratory assays, and therefore embodiments in which the claim requires the recited "instructions" to comprise structure for performing these physical steps, e.g. robotic performance, presumably with the "system" also comprising any necessary physical structure.
The specification discloses "(a) obtaining..." (p. 5) and "(b) determining..." (p. 5), but the specification does not detail how to perform said obtaining or determining regarding such robotic embodiments interpreted as within the scope of the claim as above.
For computationally-implemented, automated obtaining and determining, it is not clear that PHOSITA would have had knowledge to implement the required software and hardware.
Claim 46 reads on computationally-implemented, automated obtaining and determining embodiments and so is rejected here.
MPEP 2161.01.I "Determining Whether There Is Adequate Written Description For A Computer-Implemented Functional Claim Limitation" also pertains.
As appropriate, these rejections may be overcome, for example, (i) by narrowing to clearly supported embodiments and/or (ii) by clarifying on the record where support can be found and how that support relates to the recitations.
In general, it is requested that any claim amendment in this regard be accompanied by citations to support in the original disclosure.
MPEP 2163 generally pertains.
Nonstatutory double patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine to prevent the improper timewise extension of the "right to exclude" granted by a patent and to prevent multiple suits against an accused infringer by different assignees of the same invention (MPEP 804.II.B, 1st para.). A nonstatutory double patenting rejection is appropriate where the conflicting claims (instant v. reference) are not identical, but an examined-application claim (instant claim) is not patentably distinct from a reference claim because the instant claim is either anticipated by, or would have been obvious over, the reference claim (MPEP 804.II.B, 2nd para.).
In cases of double patenting rejections versus reference claims of pending applications, as opposed to claims of an issued patent, the rejections are provisional because the reference claims have not been patented. Presently, no rejections are provisional.
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 application or patent of the reference claim either is shown to be commonly owned with the instant application or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must comply fully with 37 CFR 3.73(b).
Applicant may wish to consider electronically filing a terminal disclaimer (MPEP 1490.V pertains, along with https://www.uspto.gov/patents-application-process/applying-online/eterminal-disclaimer). Electronic filing may lead to faster approval of the disclaimer. Also, if filing electronically, Applicant is encouraged to notify the examiner by telephone so that examination may resume more quickly.
Double patenting rejections of instant claims
Instant claims 1, 3-4, 8-9, 11-12, 16, 19-20, 22, 24, 30, 32-34, 44 and 46-47 are rejected on the grounds of nonstatutory double patenting as unpatentable over one or more claims in reference patent 12,637,714 (application 17/268,732) in view of Woodward (as cited on the 4/28/2025 IDS), Ma (as cited on the 11/18/2025 form 892), Rava (as cited on the attached form 892) and Umbarger (as cited on the 11/18/2025 form 892).
The reference patent as well as the instant application recite claims which involve determining transplant status using similarly specified SNPs.
Although the reference claims are not identical to the instant claims, in a BRI they also are not patentably distinct from the instant claims: either (i) because the instant claims recite obviously equivalent or broader limitations in comparison to the reference claims or (ii) because the instant claims recite limitations which are obvious over the cited art. It is not clear that the instant claims recite limitations which are narrower than limitations in the reference claims.
It would have been obvious in view of the cited art to modify reference claims to arrive at the rejected instant claims. Either the instant limitations are interpreted as reading on a reference limitation, or the instant limitations would have been obvious in view of the cited art. That is, to the extent that any instant claims are narrower than reference claims, then any such narrowing would have been obvious over the cited art.
Conclusion
No claim is allowed.
Applicant's amendments necessitated the new grounds for rejection in this action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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The examiner for this Office action, G. Steven Vanni, may be contacted at:
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs, II, may be reached at (571) 270-3062.
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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