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 .
Claim Status
Claims 16-20 are pending; claims 16-20 were amended in the Reply filed 9/30/2025. Claims 1-15 and 21-31 were identified as canceled in the Reply. Claim 18 remains withdrawn, claims 16-17 and 19-20 are not original claims, and are presently considered.
Election/Restrictions
Applicant’s election of the species of method represented by pending claims 16-20 in the reply filed on 9/08/2023 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The elected species is understood to be a narrow subgenus of patentably indistinct species wherein patients “with excess neutrophils” are tested for alpha-1 antitrypsin deficiency (hereafter “A1ATD”) via the analysis of a blood sample for “circulating alpha-1 antitrypsin and/or neutrophil elastase” (see, e.g., Reply filed 9/08/2023 at 8).
Following extensive search and examination, the originally elected species (or narrow subgenus) has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 16-17 and 19-20 are understood to read upon the originally elected species/subgenus.
In addition, claim 18 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/08/2023.
Claims 16-17 and 19-20 are presently considered.
Information Disclosure Statement
No IDS was filed in the RCE filed 11/08/2024.
Examiner Notes and Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 16 is representative of the pending claim scope and presently recites:
16. (Currently Amended) A method of preventing destruction, damage, or demyelination of cells by excess neutrophils in a body of a patient , the method comprising the steps of:
determining a level of neutrophil elastase in the body of the patient to determine if there is a neutrophil imbalance;
determining if the patient is alpha-1 antitrypsin deficient by:
obtaining a blood sample from the patient, and
performing an analysis of the blood sample, wherein
performing an analysis of the blood sample comprises measuring and/or testing a level of circulating alpha-1 antitrypsin in the blood sample;
determining if the patient is alpha-1 antitrypsin deficient if the level of circulating alpha-1 antitrypsin is below at least 100 mg/dl;
calculating a dosage of alpha-1 antitrypsin to administer to a patient based upon the level of circulating alpha-1 antitrypsin,
and
administering an amount of alpha-1 antitrypsin to the patient such that the patient’s circulating alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL if the patient is alpha-1 antitrypsin deficient to correct the neutrophil imbalance;
wherein the patient’s circulating alpha-1 antitrypsin level comprises the level of circulating alpha-1 antitrypsin in the blood sample and the amount of alpha-1 antitrypsin administered.
The applicable claim interpretations are set forth below.
Regarding the preamble of claim 16, which recites
…..of preventing destruction, damage, or demyelination of cells by excess neutrophils in a body of a patient …[,]
per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the preamble is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”). At most, the preamble of claim 16 may be considered to limit the patient population to patients that actually have “excess neutrophils” treatable with A1AT; however, this is incorrect in view of the “screening” steps set forth in the body of claim 16. Rather, the preamble recites the intended result that would occur upon treating a patient “with excess neutrophils”, but screening steps are understood to define what patients do or do not have “excess neutrophils” (i.e., “excess neutrophils” are reasonably inferred by the measured levels of neutrophil elastase and alpha-1 antitrypsin as set forth in the body of amended claim 16, and if alpha-1 antitrypsin levels are not “below at least 100 mg/dL” then no “preventing destruction, damage, or demyelination of cells” actually occurs in “a body of a patient with excess neutrophils”).
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
At claim 16, the “obtaining” step is understood to be satisfied by any means of obtaining a blood sample, and is understood to necessarily or inherently occur in view of prior art identifying that a plasma or serum sample of a patient has been tested.
At claim 16, the “analysis” step is understood to be satisfied by any means of analysis that is indicative of A1ATD, including genotyping or determining circulating A1AT levels. This interpretation is reasonable in view of dependent claims 17-19.
Amended claim 16 recites the limitation
administering an amount of alpha-1 antitrypsin to the patient such that the patient’s circulating alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL if the patient is alpha-1 antitrypsin deficient to correct the neutrophil imbalance.
This is understood to be a contingent limitation, wherein the recited steps are only performed “if” the stated condition occurs. Per MPEP § 2111.04(II), “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met.” Accordingly, the contingent limitation at claim 16 need not be performed in the prior art for prior art to anticipate the claim.
Claim 16 recites the step of “administering” A1AT. This is understood to encompass all methods of administration (e.g., intravenous, intraperitoneal, etc.), except for topical forms of administration.
The contingent limitation of claim 16 recites:
…..if the patient is alpha-1 antitrypsin deficient .
The phrase is deemed satisfied by any prior art assessment that deems a patient to be A1AT deficient by having circulating A1AT levels at “below at least 100 mg/dL”.
The reply filed 9/30/2025 added explanatory phrases directed to the intention for explicitly recited active method steps (e.g., “to determine if there is a neutrophil imbalance”, to correct the neutrophil imbalance”). These recitations of intended or expected results are understood to be fully satisfied by the performance of the positively recited method steps (see, e.g., MPEP § 2111.04).
Amount of A1AT administered: Claim 16 recites the limitation
if the patient is alpha-1 antitrypsin deficient, then internally administering alpha-1 antitrypsin to the patient such that the patient’s total alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL.
The recitation that A1AT is administered “such that” the patients A1AT level is “maintained in the range of 100-300 mg/dL” is a recitation of a hoped for and desired result that Applicant wants the treatment to achieve, but does not actually identify how such hoped-for result can be achieved in actual practice (e.g., if a patient is assayed as having 50 mg/dL, how much should be added to achieve 100-300 mg/dL?). For purposes of applying prior art, any prior art teaching administration of A1AT at levels expected to treat A1ATD or achieve normal A1AT circulating levels is understood to satisfy the limitation set forth at the contingent limitation of instant claim 16. Additional interpretation notes are provided below in the rejections under 35 USC 112(b).
Alpha-1 antitrypsin is also known in the prior art as SERPINA1, A1A, A1AT, AAT, PI, PI1, PRO2275, Alpha1AT, Serpin family A member 1, nNIF, Alpha-1proteinase inhibitor (A1PI), Alpha-1-antiproteinase (A1AP), and in older literature “Serum trypsin inhibitor” (STI), among other names.
Amended claim 16 as filed 9/30/2025 now recites the “wherein” clause
wherein the patient’s circulating alpha-1 antitrypsin level comprises the level of circulating alpha-1 antitrypsin in the blood sample and the amount of alpha-1 antitrypsin administered.
The meaning of this limitation and how it interacts and limits prior recitations at claim 16 is unclear because the claim refers to (i) “circulating alpha-1 antitrypsin”, (ii) a “level of circulating alpha-1 antitrypsin in the blood sample”, (iii) a “circulating alpha-1 antitrypsin level”, and (iv) “level of circulating alpha-1 antitrypsin, (v) “amount of alpha-1 antitrypsin”, (vi) alpha-1-antitrypsin deficient” and (vii) “dosage of alpha-1 antitrypsin” (Examiner has attempted to mark these terms in Claim 16 as shown below):
16. (Currently Amended) A method of preventing destruction, damage, or demyelination of cells by excess neutrophils in a body of a patient, the method comprising the steps of:
determining a level of neutrophil elastase in the body of the patient to determine if there is a neutrophil imbalance;
determining if the patient is alpha-1 antitrypsin deficient by:
obtaining a blood sample from the patient, and
performing an analysis of the blood sample, wherein
performing an analysis of the blood sample comprises measuring and/or testing a level of circulating alpha-1 antitrypsin in the blood sample;
determining if the patient is alpha-1 antitrypsin deficient if the level of circulating alpha-1 antitrypsin is below at least 100 mg/dl;
calculating a dosage of alpha-1 antitrypsin to administer to a patient based upon the level of circulating alpha-1 antitrypsin,
and
administering an amount of alpha-1 antitrypsin to the patient such that the patient’s circulating alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL if the patient is alpha-1 antitrypsin deficient to correct the neutrophil imbalance;
wherein the patient’s circulating alpha-1 antitrypsin level comprises the level of circulating alpha-1 antitrypsin in the blood sample and the amount of alpha-1 antitrypsin administered.
The phrases (e.g., “level of circulating alpha-1-antitrypsin” and “circulating alpha-1-antitrypsin level”) are similar, but different, and therefore each phrase is reasonably presumed to refer to different things; this assumption is reasonable and consistent with court guidance because "When different words or phrases are used in separate claims, a difference in meaning is presumed" (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005)). The step reciting
determining if the patient is alpha-1 antitrypsin deficient if the level of circulating alpha-1 antitrypsin is below at least 100 mg/dl…
requires knowing the “level of circulating alpha-1-antitrypsin”. Critically, the step of
calculating a dosage of alpha-1 antitrypsin to administer to a patient based upon the level of circulating alpha-1 antitrypsin, …
also depends upon knowing the “level of circulating alpha-1-antitrypsin”. Accordingly, the “dosage of alpha-1-antitrypsin” and the determination that a patient is “alpha-1-antitrypsin deficient” depends upon knowing or assaying the “level of circulating alpha-1-antitrypsin”. However, it is unclear how the parameters represented by the three different phrases of “level of circulating alpha-1-antitrypsin”, “circulating alpha-1-antitrypsin level”, and the “level of circulating alpha-1-antitrypsin in the blood sample” are interrelated, as required to practice the claimed invention.
The terms “circulating alpha-1-antitrypsin level” and the “level of circulating alpha-1-antitrypsin in the blood sample” are presumably related in the manner set forth in the final three lines of the amended, independent claim, but the definition is circular in nature:
administering an amount of alpha-1 antitrypsin to the patient such that the patient’s circulating alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL if the patient is alpha-1 antitrypsin deficient to correct the neutrophil imbalance;
Accordingly, to determine the “amount of alpha-1-antitrypsin” to administer to a patient, an artisan must first know the patient’s circulating alpha-1 antitrypsin level. But then the amended claim confusingly states
wherein the patient’s circulating alpha-1 antitrypsin level comprises the level of circulating alpha-1 antitrypsin in the blood sample and the amount of alpha-1 antitrypsin administered.
This means that to know the patient’s circulating alpha-1 antitrypsin level, an artisan must first know the amount of alpha-1 antitrypsin administered, but to know the amount of alpha-1 antitrypsin administered, an artisan must first know the patient’s circulating alpha-1 antitrypsin level -this is a circular definition. Accordingly, as drafted, an artisan cannot know either the patient’s circulating alpha-1 antitrypsin level or the amount of alpha-1 antitrypsin administered, without first knowing the other; accordingly, these definitions are flawed.
Patient population: Claim 16 is understood to be a screening method, wherein any patient having “below at least 100 mg/dL” of A1AT is reasonably considered to have a “neutrophil imbalance”. Accordingly, the patient population at claim 16 encompasses all humans that may benefit by screening for “excess neutrophils in [their] body” (see claim 16) by measuring neutrophil elastase and A1AT. This patient population is understood to broadly include all humans, and to especially include any prior art patient population at risk of AATD.
It is the Examiner’s understanding that the Specification admits that detection assays for determining if a patient is A1AT deficient were prior art elements (see, e.g., Spec. filed 11/16/2021 at 16-17, describing art-recognized means of testing for A1ATD). Applicant apparently disagrees with this assessment, but this is not persuasive because the assertion fails to specifically identify any other reasonable, alternative interpretation of the cited portion of the originally filed disclosure (see, e.g., Reply filed 9/30/2025 at 5 at § Claim Interpretation).
It is the Examiner’s understanding that the Specification admits that protein replacement therapy wherein A1ATD is treated by administering A1AT was a prior art methodology (see, e.g., Spec. filed 11/16/2021 at 23, describing FDA approval of Glassia). Applicant apparently disagrees with this assessment, but this is not persuasive because the assertion fails to specifically identify any other reasonable, alternative interpretation of the cited portion of the originally filed disclosure (see, e.g., Reply filed 9/30/2025 at 5 at § Claim Interpretation).
It is the Examiner’s understanding that Applicant acknowledges the admissions of record identified in the two preceding paragraphs (see, e.g., Reply filed 4/10/2024 at 5-6 at bridging ¶; see also Reply filed 11/08/2024 at 5 at § Claim Interpretation; see, e.g., Reply filed 9/30/2025 at 5 at § Claim Interpretation).), but states that “the claimed invention is novel” without addressing any errors in the originally filed disclosure or the Examiner’s interpretation. Such conclusory statements are not persuasive because such statements fail to reconcile the admissions in the original disclosure with any point of novelty in the amended claims.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejections of claims 16-17 and 19-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite have been successfully overcome in part by the amendments filed 9/30/2025 to claims 16-17 and 19-20, including the amendment deleting “excess neutrophils” from claim 16. Remaining or new issues are addressed in a revised rejection below.
The rejection of claim 19 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form, is withdrawn in view of the amendments filed 9/30/2025 to claims 16 and 19.
New or Revised Claim Rejections as Necessitated by Applicant Amendments
Claim Rejections - 35 USC § 112(b)
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 16-17 and 19-20 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 16 and 20 recite the phrase “…total alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL”, which contains the indefinite reference to a range of 100-300 mg/dL of alpha-1 antitrypsin. The range is indefinite because in the A1AT deficiency arts, it is well-understood that the measured level of AAT varies depending upon the exact quantitative test utilized1. Specifically, the “Normal Range” and “Protective Thresholds” differ depending upon whether or not a blood sample is processed using Radial immunodiffusion or Nephelometry (see, e.g., Standards2003 at 826 at col I at 1st ¶, Table 4 on 826, reproduced in part below):
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150
998
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Accordingly, the recited range at claims 16 and 20 differ substantially in meaning if the range refers to a measurement performed by radial immunodiffusion rather than nephelometry, or vice versa. Specifically, 100 mg/dL is above the low end of the “normal range” for nephelometry, but is below the low end of the “normal range” for radial immunodiffusion (see id), but is within the “protective threshold” of each (see id). Therefore, it is uncertain whether or not the claimed invention is intended to “maintain” a “total apha-1 antitrypsin level” that is below or above the “normal range” as measured by radial immunodiffusion or nephelometry. Per MPEP § 2173, the primary purpose of 35 USC §112(b) is “to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”; here, in the absence of unambiguous guidance regarding how the range of 100-300 mg/dL should be determined (e.g., by radial immunodiffusion or nephelometry), an artisan would not be reasonably apprised of whether or not the claimed invention was attempting to achieve a “protective threshold” of A1AT within or below the normal ranges taught in the prior art. Accordingly, claims 16 and 20 are rejected as indefinite.
Claim 16 is indefinite because the term “alpha-1 antitrypsin deficient” ostensibly appears to be used in a manner different from the prior art. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). Here, the term “alpha-1 antitrypsin deficient” at claim 16 is used by the claim to mean “below at least 100 mg/dL”, while the accepted meaning of alpha-1 antitrypsin deficiency is not defined utilizing “total alpha-1 antitrypsin”, but instead depends upon genetic analysis because
Although measurement of serum or plasma AAT levels for the diagnosis of AATD may detect individuals who are severely deficient . . . . [a] caveat of using AAT levels for diagnosis is that heterozygous carriers may be missed as their AAT levels may overlap with those of nondeficient individuals…2
Furthermore, the prior art teaches that multiple patients with AATD may exhibit A1AT serum levels within the range of “100-300 mg/dL” (see, e.g., Hurley3 at Table on 2035, reproduced below):
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1078
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Accordingly, the term “alpha-1 antitrypsin deficient” at instant claim 16 appears to differ from the art-recognized meaning and usage of the term “alpha-1 antitrypsin deficiency”, which is used to indicate that patients are “alpha-1 antitrypsin deficient”, because the prior art definition does not depend upon A1AT levels being “at least below 100 mg/dL” as a diagnostic threshold. Accordingly, claim 16 is rejected as indefinite because Applicant appears to be utilizing a different definition and standard for the term “alpha-1 antitrypsin deficient” relative to the art-recognized usage, but the instant Specification fails to clearly redefine the metes and bounds of the term as currently utilized, and therefore it is unclear if Applicant is wholly attempting to replace the prior art definition, or if the Applicant is adding an additional requirement of A1AT levels to the existing prior art definition. This distinction changes the pending claim scope, and it is unclear which definition is correct.
For purposes of applying prior art, any prior art-recognized patient-population positively identified as deficient in alpha-1 antitrypsin or as having a phenotype or genotype of alpha-1 antitrypsin deficiency, using any blood test (e.g., plasma, serum, spots), wherein the reported range of associated serum AAT concentration includes values under 100 mg/dL is deemed to be “alpha-1 antitrypsin deficient” within the scope of the pending claims (i.e., PiZZ, PiSZ, PiSS, PiMZ, PiMS, etc.).
Claims 16 and 20 are rejected as indefinite; claim 16 is representative of the issue and recites the limitation
…administering an amount of alpha-1 antitrypsin to the patient such that the patient’s total alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL.
This limitation recites a hoped-for and desired outcome (i.e., that A1AT levels are “maintained in the range of 100-300 mg/dL”), which requires knowledge of a functional relationship between “administered” A1AT concentrations and resulting A1AT levels that are “maintained in the range of 100-300 mg/dL”. However, no functional relationship between administered dosages and resulting levels of “total alpha-1 antitrypsin” have been disclosed on record. Therefore, there exists a substantial and material concern, namely, how much A1AT must be “administered” to a given patient to “maintain” A1AT levels in the range of 100-300 mg/dL? This question is material to the claim scope, but multiple issues convolute the answer because (i) the range of “100-300 mg/dL” varies substantially in meaning depending upon how the measurement of the range is performed (see preceding rejection of claim 16 addressing the differences in measuring A1AT using either radial immunodiffusion or nephelometry, set forth above, and incorporated herein); and (ii) the typical range of A1AT levels vary substantially in patients depending upon various circumstances4. Therefore, it is unclear what amount of A1AT should be “administered” to a given patient in order to specifically “maintain” A1AT levels within the range of 100-300 mg/dL, and no guidance on the functional relationship between administration route, A1AT measurement types, patient variability, and the desired outcome has been provided on record.
For purposes of applying prior art, the requirement to “administer” A1AT “such that” the patient’s “total alpha-1 antitrypsin level is in the range of 100-300 mg/dL” is deemed fully satisfied by prior art that teaches the “[t]ypical augmentation therapy dosage for AATD patients”, namely “60mg/kg of weight”, which is reasonable because the original disclosure states that “…This range is described as being between 100-300 mg/dL. Previous AATD patients have only been brought up to the lower end of this range….” (see, e.g., Spec. filed 11/16/2021 at 63 at 1st partial ¶; see also id. at 23 at 1st full ¶). Accordingly, it is reasonably inferred that the previous dosage of “60 mg/kg of weight” treatment is sufficient to bring AATD patients “up to the lower end of” the range of 100-300 mg/kg as presently claimed (see, e.g., Spec. filed 11/16/2021 at 23 at 1st full ¶, 63 at 1st partial ¶).
Amended claim 16 now recites the step of “determining a level of neutrophil elastase in the body of the patient to determine if there is a neutrophil imbalance”, which renders the claim scope indefinite as explained herein. Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for failing to interrelate essential elements of the claimed invention, such omission amounting to a gap between the necessary structural connections (see, e.g., MPEP § 2172.01, § 2173.05(k)). The omitted structural cooperative relationships are: how the step of “determining a level of neutrophil elastase in the body of the patient” is related to the performance of any other step or parameter set forth at claim 16. Notably, the step of “determining a level of neutrophil elastase in the body of the patient” is unrelated and not interrelated to (1) the identification of a patient population, (2) the determination of if a patient is A1AT deficient, (3) the administration of A1AT, (4) the “calculating” step, and (5) unrelated to any parameter recited in the preamble. Accordingly, this step, which was newly added in the Reply filed 11/08/2024, appears to be wholly unrelated to the any other step, compound, parameter, or aspect of the claim. Furthermore, the performance of the step does not further achieve any stated purpose or treatment, and appears to merely be recited to distinguish the claimed invention relative to the prior art, without further use. See MPEP § 2172.01.
Amended claim 16, as filed 9/30/2025 is indefinite because it relies upon circular definitions wherein two terms or phrases cannot be evaluated without first knowing the other term, which renders the claim scope indefinite because it is unclear how an artisan could avoid infringement of ill-defined parameters dependent upon circular definitions. "When different words or phrases are used in separate claims, a difference in meaning is presumed" (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005)). At amended claim 16, the terms “circulating alpha-1-antitrypsin level”, “level of circulating alpha-1-antitrypsin in the blood sample”, and “amount of alpha-1 antitrypsin” are presumably related in the manner set forth in the final three lines of the amended, independent claim, but the definition is circular in nature:
administering an amount of alpha-1 antitrypsin to the patient such that the patient’s circulating alpha-1 antitrypsin level is maintained in the range of 100-300 mg/dL if the patient is alpha-1 antitrypsin deficient to correct the neutrophil imbalance;
Accordingly, to determine the “amount of alpha-1-antitrypsin” to administer to a patient, an artisan must first know the patient’s “circulating alpha-1 antitrypsin level”. But then the amended claim confusingly states
wherein the patient’s circulating alpha-1 antitrypsin level comprises the level of circulating alpha-1 antitrypsin in the blood sample and the amount of alpha-1 antitrypsin administered.
This means that to know the patient’s circulating alpha-1 antitrypsin level, an artisan must first know the amount of alpha-1 antitrypsin administered, but to know the amount of alpha-1 antitrypsin administered, an artisan must first know the patient’s circulating alpha-1 antitrypsin level; accordingly, the amended claim creates a circular definition. Accordingly, as drafted, an artisan cannot know either the patient’s circulating alpha-1 antitrypsin level or the amount of alpha-1 antitrypsin administered, without first knowing the other. Accordingly, the pending claim scope is prima facie indefinite, because close prior art exists (see rejection under 35 USC 103, below), and it is prima facie unclear how to interpret such circular definitions in a manner sufficient to avoid infringement.
Claim 20 refers to “the step of internally administering….” At lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, it is reasonably inferred that claim 20 is directed to the amended step at claim 16 reciting “administering”.
Claims 17 and 19-20 depend directly or indirectly from an indefinite base claim, and do not resolve the indefiniteness of the base claim. Accordingly, claims 17 and 19-20 are rejected as indefinite.
Claims 16-17 and 19-20 are rejected.
Response to Arguments Regarding 35 USC 112(b)
Applicant's arguments filed 09/30/2025 regarding the Rejections under 35 USC 112(b), have been fully considered but they are not persuasive. It is the Examiner’s understanding that Applicant traverses the rejection at pages 6-7 (see, e.g., Reply filed 9/30/2025 at 6 at 4th full ¶ to page 7 at 1st full ¶). These arguments are addressed below.
It is the Examiner’s understanding that Applicant provides a conclusory statement identifying that they “traverse” the rejections, but “to facilitate prosecution” have amended claim 16 (see, e.g., Reply filed 9/30/2025 at 6 at 4th full ¶ to page 7 at 1st full ¶). However, zero explanation of how such amendments resolve the pending rejections or otherwise address the merits of the rejections was provided. Accordingly, the Examiner is uncertain how the response filed 9/30/2025 specifically addresses the rejections of record, because Applicant fails to address the merits of the rejections completely. Applicant is again advised that a response that addresses each issue independently and individually, coupled with specific identification of a portion of the disclosure that addresses the ambiguity identified by the Examiner, would substantially further facilitate prosecution.
Examiner notes that Applicant refers to unclaimed limitations in the Specification (see, e.g., Reply filed 9/30/2025 at 6 at 4th full ¶, referring to p. 25, and MM allele individuals). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Accordingly, the rejections are maintained as revised above. All revisions were necessitated by Applicant’s amendments.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 16-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Campos5 in view of Ho6, and as evidenced by Standards20037.
Claim interpretation: The applicable claim interpretation is set forth above in a separate section, which is incorporated herein. Claim 16 has been rejected as indefinite above. For purposes of the instant rejection, claim 16 is understood to be a screening method with a contingent treatment limitation used only if a patient has AAT levels of less than 100 mg/dl, wherein the applicable patient population is understood to include patients having α1 Antitrypsin deficiency (hereafter “AATD”). Additional claim interpretations are set forth below.
Regarding instant claims 16-17, 19-20, and the applicable patient population, the patient population is reasonably understood to encompass patients having circulating alpha-1 antitrypsin (AAT) levels “below at least 100 mg/dL” (see, e.g., instant claim 16). Campos discloses that α1 Antitrypsin deficiency (hereafter “AATD”) is a prior art condition, having known diagnostic standards, and known treatment options (see, e.g., Campos at title, abs, 150 at § Introduction), wherein circulating AAT levels are identified as “below normal” (see, e.g., Campos at 152 at col II at 1st ¶). Regarding instant claims 16 and the testing of circulating α1 Antitrypsin as “below at least 100 mg/dL”, Campos identifies that patients in need of treatment for AATD have “AAT levels” that are “below normal” (see, e.g., Campos at 152 at col II at 1st ¶, Table 1 on 153, 155 at col I at 1st partial ¶). Campos does not explicitly address “what is normal and ‘below normal’ for AAT levels”, but such knowledge was well-known in the art as evidenced by Standards2003. Standards2003 evidences that “normal” depends upon the test administered (see, e.g., Standards2003 at 826 at col I at 1st ¶, Table 4 on 826), but reports that the normal Phenotype (i.e., PI*MM) is associated with approximately 150-350 mg/dL, whereas AATD phenotypes of PI*MZ, PI*SZ, and PI*ZZ are associated with values below 100 mg/dL (see, e.g., Standards2003 at Table 3 on 825, reproduced in part below; see also id. at 824, discussing phenotypes):
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Accordingly, one of ordinary skill in the art reading Campos would readily appreciate that “below normal” would refer to any value “below” 150-350 mg/dL (see, e.g., id.; see also MPEP § 2144.05 (I), noting “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”, and here the range of “below 150 mg/dL” and “below 100 mg/dL” substantially overlap). Accordingly, Campos identifies that it is routine in the prior art to measure circulating levels of AAT, and to determine if they are “below normal” (see, e.g., Campos at 152 at col II at 1st ¶, Table 1 on 153, 155 at col I at 1st partial ¶), which would necessarily be understood to include values below “below 150 mg/dL”, including values associated with AATD phenotypes of PI*MZ, PI*SZ, and PI*ZZ. Regarding instant claims 16, 20, and the treatment of patients who have confirmed AATD and low AAT by administering AAT to the patient, Campos discloses that the general “Treatment of AATD” is known (see, e.g., Campos at 154 at col II at § Treatment of AATD to page 158 at 1st partial ¶). Specifically, Campos identifies that the current treatment for AATD for “individuals with abnormal AAT genotypes who have AAT levels below . . . [normal]”8, and explicitly identifies that routine treatment includes weekly infusions of AAT at 60 mg/kg to 120 mg/kg, or higher (doubling of the weekly dosage) (see, e.g., Campos at 157-158 at bridging ¶), and that such treatments have “been proved to restore plasma AAT concentrations to protective levels” (see, e.g., Campos at 157 at col I at final ¶), and even to “elevate[] AAT trough levels to the normal range” (see, e.g., Campos at 157-158 at bridging ¶, emphasis added). As noted above, the “normal range” would be readily understood to be approximately 150-350 mg/dL (see, e.g., Standards2003 at Table 3 on 825). Critically, “150-350 mg/dL” overlaps with the claimed range of “100-300 mg/dL” (see, e.g., MPEP § 2144.05 (I), noting “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”). Accordingly, an artisan would at once envisage treating AATD patients with 60-120 mg/kg (or higher) weekly doses of α1 Antitrypsin, which would be predicted and expected to return AAT levels to normal, thereby treating the symptoms of AATD. In sum, the prior art of Campos teaches that methods of testing for AATD by serum, phenotyping, and genotyping, and then treating AATD by AAT augmentation therapy by administering 60 or 120 mg/kg weekly, is simply the “current best practice in testing and augmentation therapy” for AATD (see, e.g., Campos at title, abs). Regarding instant claims 16-17, 19, and genotyping, Campos teaches that “[t]esting strategies usually imply a combination of measures of α1 Antitrypsin (AAT) levels, phenotyping and genotyping. . . .” (see, e.g., Campos at abs). Campos identifies that analysis of a patient at risk includes “measurement of serum or plasma AAT levels for the diagnosis of AAT” (see, e.g., Campos at 152 at col I-II at § Laboratory diagnosis of AATD), which is combined with phenotyping and genotyping (see id), because serum measurements alone, while capable of detecting individuals who are severely AAT deficient, cannot discern underlying ATTD types (see id). Accordingly, Campos identifies that serum measurements of AAT, phenotyping, and genotyping assays are routine and standard in the AATD arts for patients at risk of AATD. Therefore, an artisan would at once envisage performing serum measurements, phenotyping, and genotyping such patients to achieve a diagnostic detection of AATD and the specific type of AATD in a patient as explicitly stated by Campos (see, e.g., Campos at title, abs, 152 at col I-II at § Laboratory diagnosis of AATD).
Campos as evidenced by Standards2003 differs from the amended claim scope as follows: Campos does not teach a step of “determining a level of neutrophil elastase in the body of a patient” as required by amended claim 16.
However, the step of “determining a level of neutrophil elastase in the body of a patient” appears wholly unrelated to the diagnosis and treatment of AATD by administering AAT in amounts to maintain AAT at normal levels in a patient. Accordingly, the step of measuring neutrophil elastase appears to be unrelated to the other steps recited at instant claim 16.
Ho9 identifies that Neutrophil elastase is an art-recognized diagnostic marker (see, e.g., Ho at title, abs), and was recognized circa 2014 as associated with tumorigenesis, tumor proliferation, metastasis, and colorectal cancer (see, e.g., Ho at title, abs, 474 at col I-II at bridging ¶, 474 at col II at 1st full ¶). Ho identifies that methods for determining levels of neutrophil elastase in the body of patients was known circa 2014 (see, e.g., Ho at title, abs, 475 at col II, 476 at Fig. 3, 477-478 at bridging ¶). Accordingly, the newly added step at claim 16 was already known in the prior art, practiced in the prior art, and neutrophil elastase was an art-recognized biomarker for associated with tumorigenesis, tumor proliferation, metastasis, and colorectal cancer.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
The claimed invention is the combination of the known techniques of (i) screening for and treating ATTD by administering ATT as taught by Campos, and (ii) screening of Neutrophil elastase as a biomarker for associated with tumorigenesis, tumor proliferation, metastasis, and colorectal cancer as taught by Ho), wherein such combination would yield predictable results, namely a combined screening method for ATT levels and Neutrophil elastase, wherein, depending on the levels of each, a subject would either be treated for ATTD by administering ATT, and/or otherwise be treated for colorectal cancer and monitored for tumor proliferation and metastasis as taught by Ho. Critically, each prior art method merely performs its art-recognized function in combination as it does separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to follow the express teachings of the prior art to test for and treat known diseases using known diagnostics and known treatment regimes at known dosages. Combining such steps amounts to screening a patient for known illnesses and markers of illness, which is well-within the ordinary skill in the art.
No unexpected results commensurate in scope with the requirements of MPEP § 716.01 or §716.02 have been placed on record to date.
Accordingly, claims 16-17 and 19-20 are rejected.
Response to Arguments Regarding 35 USC 103
Applicant's arguments filed 09/30/2025 regarding the Rejections under 35 USC 103, have been fully considered but they are not persuasive. It is the Examiner’s understanding that Applicant traverses the rejection at pages 7-8 (see, e.g., Reply filed 9/30/2025 at 7 at 3rd full ¶ to page 8 at 1st partial ¶). These arguments are addressed below.
It is the Examiner’s understanding that Applicant recites case law and generalities regarding 35 USC 103 (see, e.g., Reply filed 9/30/2025 at 7 at 3rd full ¶). These statements are neither disputed nor dispositive of obviousness, and fail to address or traverse the merits of the rejection.
It is the Examiner’s understanding that Applicant is alleging that the prior art reference of Ho and Campos are non-analogous art (see, e.g., Reply filed 9/30/2025 at 7 at final ¶ to page 8 at 1st partial ¶).
It is the Examiner’s understanding that Applicant alleges multiple conclusory statements, presumably supported by the following:
Campos teaches "weekly infusions of AAT at 60 mg/kg" and Ho teaches "under normal physiological condition, the activity of secreted NE from neutrophils is regulated by protease inhibitor such as alpha-I anti-trypsin (AIA T). However, in tumor circumstances, AIA T is down-regulated in tumor tissues. The imbalance between NE and anti-protease also enhances the NE-induced tumor development." Therefore, the rejections are improper, and Applicant respectfully requests withdrawal of the rejections. (see, e.g., Reply filed 9/30/2025 at 7 at final ¶ to page 8 at 1st partial ¶).
No coherent argument unambiguously articulating any support for the conclusory statements (i.e., “the rejections are improper”, or statements alleging a missing teaching) has been found in this statement because the statement fails to (i) identify any missing teaching, (ii) fails to address the merits of the rejection, and (iii) fails to articulate any specific argument supported by evidence relevant to the claimed invention and rejection at issue. First, the relevance of “tumor circumstances” or “NE-induced tumor development” is not identified and such limitations are not recited in the claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Second, if Applicant means to allege that the references at issue are non-analogous art, this is not persuasive because it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Campos is clearly related to A1AT and Ho is clearly related to analysis of neutrophil elastase, which are both claimed subject matter, and therefore directly pertinent to the claimed invention. Accordingly, such arguments are not persuasive. Third, if Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date. Fourth, if Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. Fifth, if Applicant means to allege that prima facie obviousness was not established on the merits because one or more limitations was not addressed, this is not persuasive because Applicant fails to identify any limitations that were not fully addressed and considered in the rejection (see, e.g., Reply filed 9/30/2025 at 7 at final ¶ to page 8 at 1st partial ¶). In sum, Applicant’s statements (see, e.g., Reply filed 9/30/2025 at 7 at final ¶ to page 8 at 1st partial ¶) do not support their conclusion, at least because the statements fail to address the merits of the rejection by identifying a single limitation that was not fully addressed, and such statements do not rebut the determinations, citations, and statements supporting a determination of obviousness as set forth in the rejection. The Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007)