DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1 and 3-11 are pending in this application.
Applicant’s amendment to the claims filed 05/20/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 05/20/2026 is acknowledged.
Applicant’s remarks filed on 05/20/2026 in response to the non-final rejection mailed on 11/21/2025 are acknowledged and have been fully considered.
The objections to and rejections of claim 2 are withdrawn in view of the cancelation of the claim.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 02/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Objections to Specification
The objections to the specification are withdrawn in view of the amendments to address the use of trademarks.
Claim Objections
The objections to claim 1 are withdrawn in view of the amendments to recite
“a first composition containing polyoxyethylene monostyrenated phenyl ether” and “wherein the first reagent composition has one, two, or three activities”.
The objection to claim 8 is withdrawn in view of the amendment to recite “wherein (a) the first reagent composition contains a hydrogen donor and not a coupler, and the second reagent contains a coupler and not a hydrogen donor, or (b) the first reagent composition contains a coupler and not a hydrogen donor, and the second reagent composition contains a hydrogen donor and not a coupler”.
Claims 1 and 9 are objected to for the typo “to quantify the sdLDL-C to quantify cholesterol in a remaining lipoprotein”. In the interest of improving claim form, Applicant should consider an amendment to recite either “to quantify the sdLDL-C in a remaining lipoprotein” or “to quantify cholesterol in a remaining lipoprotein”.
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 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 first reagent configured to act on the sample” recited in claims 1 and 9-11 each, and
“a second reagent composition configured to quantify the sdLDL-C to quantify cholesterol in a remaining lipoprotein” recited in claims 1 and 9-11 each.
Because these claim limitation(s) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they 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(b)
The rejection of claims 1 and 6-8 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention is withdrawn in view of the amendment to claim 1 to recite “wherein the first reagent composition has one, two, or three activities”.
Claims 1 and 3-11 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is newly stated and necessitated by claim amendment.
Regarding claims 1 and 9-11, the claim limitations:
“the first reagent configured to act on the sample”, and
“a second reagent composition configured to quantify the sdLDL-C to quantify cholesterol in a remaining lipoprotein”
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, as the disclosure is devoid of any structure that performs the function as recited in the claim. Therefore, the claims are indefinite and are rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claims so that the claim limitations 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 claims, 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 1 (claims 3-8 dependent therefrom) and 9-11 recite “the first reagent” in line 5 of claim 1 and line 4 of claims 9-11 each. There is insufficient antecedent basis for this limitation in the claims.
Claims 3-5 are indefinite for the phrase “the reagent composition” in claims 3-5. As written, it is unclear as to whether the recited “reagent composition” is in reference to the “first reagent composition” or the “second reagent composition”.
Claim 6 is indefinite for the recitation of “the reagent composition according to claim 1”, as it is unclear whether the recited “reagent composition” is in reference to the “first reagent composition” or the “second reagent composition” recited in claim 1.
Response to Remarks: beginning on page 9 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends the instant claim amendments obviate the rejection of record.
Applicant’s remarks are considered and found not convincing, as the instant amendments have necessitated new grounds of rejection set forth above.
Claim Rejections - 35 USC § 112(a)
Claim Interpretation: The claims are drawn to a reagent composition kit for quantifying small dense LDL cholesterol (sdLDL-C) in sample comprising a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and a degree of polymerization in the first reagent is 5 or more or 80 or less.
The phrase “for quantifying sdLDL-C in a sample” is considered an intended use of the claimed reagent composition kit, and therefore is not structurally limiting (see MPEP 2111.02). In view of the claim interpretation under 35 USC 112(f) and the indefiniteness of the claims stated above, the phrases “configured to act on the sample” and “configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein” are functional limitations drawn to the intended use of the reagent composition kit and do not impart any structural limitations on the reagent composition or its components (see MPEP 2111.02). As such, the second reagent composition recited in the claims is considered structurally unlimited, and corresponds to a genus of reagent compositions that are considered widely variant with respect to structure.
A. Claims 1 and 3-11 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
The instant rejection is maintained from a previous office action, and any newly recited portion is necessitated by claim amendment.
MPEP § 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163.II.A.3.(a).ii) states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
According to § MPEP 2163.II.A.3.(a).ii), “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. According to MPEP § 2163, “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient."
The claims are drawn to or recite a genus of reagent compositions. As stated above, the genus of reagent compositions is structurally unlimited. In this case, the genus of recited reagent compositions encompasses species that are considered to be widely variant with respect to structure.
The specification discloses the following representative species of the genus of recited reagent compositions:
a composition comprising PIPES buffer, cholesterol esterase, cholesterol oxidase, sphingomyelinase, peroxidase, bovine serum albumin, TOOS, 4AA, and a surfactant that is either (1) POE-MS-PE with degree of polymerization of 11-33, (2) POE-MS-PE with degree of polymerization of 13-37, or (3) POE-MS-PE with degree of polymerization of 50-80, and
a composition comprising PIPES buffer, cholesterol esterase, cholesterol oxidase, sphingomyelinase, catalase, ascorbate oxidase, bovine serum albumin, TOOS, and a surfactant that is either (1) POE-MS-PE with degree of polymerization of 11-33, (2) POE-MS-PE with degree of polymerization of 13-37, or (3) POE-MS-PE with degree of polymerization of 50-80.
Regarding the level of skill and knowledge in the art of cholesterol quantification, Li et al. (J Food Drug Anal, 2019, 27:375; cited on the attached Form PTO-892; herein Li) reviews various methods of quantifying cholesterol including classical chemical methods, fluorometric and colorimetric enzymatic assays, and analytical instrumental approaches each with distinctive advantages [p 378, col 1, para 1], and that each utilize reagent compositions comprising structurally variable components, for example, chemicals such as hydroxide, hexane, acetic anhydride-sulfuric acid, acetyl chloride, betaine aldehyde, or enzymes such as cholesterol esterase, cholesterol oxidase [Table 1]. While the methods reviewed by Li include examples of well-known reagent compositions comprising distinct chemicals or enzymes, Li acknowledges that for enzymatic assays, for example, the assays may not be strictly selective for cholesterol determination as they can act with other sterols, and additionally that chemicals present in the sample might interact with hydrogen peroxide that is intended to generate the required fluorescence to be measured in the method, which can result in bias for cholesterol determination [p 379, col 1, para 1]. As a result, Li discloses methods using gas and liquid chromatography that are more commonly used for cholesterol quantification as they are widely accepted to be more reliable, sensitive and accurate than other methods [p 379, beginning col 1, para 2], therefore indicating the high level of unpredictability in the field of cholesterol quantification with different reagent compositions.
In view of the high level of unpredictability in the art of cholesterol quantification, because the genus of reagent compositions is widely variant with respect to structure, and the specification discloses the actual reduction to practice of only six representative species among a widely variant genus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of reagent compositions. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
B. Claims 1 and 3-11 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a reagent composition as described in Examples 1 and 3, does not reasonably provide enablement for all reagent compositions as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The instant rejection is maintained from a previous office action, and any newly recited portion is necessitated by claim amendment.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The nature of the invention: According to the specification “LDL cholesterol can be simply and inexpensively quantified without requiring a lipoprotein aggregating agent that increases the turbidity of the reaction solution, without limitation on the enzymes to be used, and without the need to add another new enzyme in the step of reacting LDL cholesterol” at para 0002, and “The present invention provides a technique for measuring sdLDL-C with excellent accuracy” at para 0005.
The object of the invention is therefore to provide a simple and inexpensive quantification method for accurate measurement of sdLDL-C.
The breadth of the claims: The claims recite (in relevant part) a reagent composition comprising a second reagent composition. As stated above, the reagent composition is considered to be structurally unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
As noted above, the reagent composition is considered to be structurally unlimited. The reference of Li reviews various methods of quantifying cholesterol including classical chemical methods, fluorometric and colorimetric enzymatic assays, and analytical instrumental approaches each with distinctive advantages [p 378, col 1, para 1], and utilize reagent compositions comprising structurally variable components, for example, chemicals such as hydroxide, hexane, acetic anhydride-sulfuric acid, acetyl chloride, betaine aldehyde, or enzymes such as cholesterol esterase, cholesterol oxidase [Table 1]. While the methods reviewed by Li include examples of well-known reagent compositions comprising distinct chemicals or enzymes, Li acknowledges that for enzymatic assays, for example, the assays may not be strictly selective for cholesterol determination as they can act with other sterols, and additionally that chemicals present in the sample might interact with hydrogen peroxide that is intended to generate the required fluorescence to be measured in the method, which can result in bias for cholesterol determination [p 379, col 1, para 1]. As a result, Li discloses methods using gas and liquid chromatography that are more commonly used for cholesterol quantification as they are widely accepted to be more reliable, sensitive and accurate than other methods [p 379, beginning col 1, para 2], therefore indicating the high level of unpredictability in the field of cholesterol quantification with different reagent compositions.
As such, one of skill in the art would recognize a high level of unpredictability that all reagent compositions as encompassed by the claims would maintain the desired activity/utility.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of the recited reagent compositions:
a composition comprising PIPES buffer, cholesterol esterase, cholesterol oxidase, sphingomyelinase, peroxidase, bovine serum albumin, TOOS, 4AA, and a surfactant that is either (1) POE-MS-PE with degree of polymerization of 11-33, (2) POE-MS-PE with degree of polymerization of 13-37, or (3) POE-MS-PE with degree of polymerization of 50-80, and
a composition comprising PIPES buffer, cholesterol esterase, cholesterol oxidase, sphingomyelinase, catalase, ascorbate oxidase, bovine serum albumin, TOOS, and a surfactant that is either (1) POE-MS-PE with degree of polymerization of 11-33, (2) POE-MS-PE with degree of polymerization of 13-37, or (3) POE-MS-PE with degree of polymerization of 50-80.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of making reagent compositions for the determination of cholesterol were known at the time of the invention, it was not routine in the art to make all reagent compositions as broadly encompassed by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Response to Remarks: beginning on page 9 of Applicant’s response to rejections under 35 USC 112(a); Applicant in summary contends the instant rejections limit the claims such that one of skill in the art would extend the value of the six disclosed species in the specification to the remaining species in the genus of reagent compositions.
Applicant has not responded to the scope of enablement rejection under 35 USC 112(a), however Applicant’s remarks are considered a bona fide attempt to respond to the rejections of record set forth in the non-final office action mailed 11/21/2025.
Applicant’s remarks are considered and found not convincing. As stated above, the instant amendments to the claims do not provide any structural limitations to the second reagent composition, and as such the second reagent composition is structurally unlimited and drawn to a genus that is considered widely variant with respect to structure. Therefore undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention, and one of skill in the art would recognize the applicant was not in possession of the recited genus of reagent compositions.
Claim Rejections - 35 USC § 102
The rejection of claims 1 and 3-5 under 35 U.S.C. 102(a)(1) as being anticipated by US 2010/035288 (cited on the IDS filed 09/09/2024; herein Denka) is withdrawn in view of the amendment to claim 1 to recite “a degree of polymerization is 5 or more and 80 or less”, as Denka does not disclose a reagent with a degree of polymerization is 5 or more and 80 or less.
Claim Rejections - 35 USC § 103
The rejection of claims 6-8 under 35 U.S.C. 103 as being unpatentable over Denka is withdrawn in view of the amendment to claim 1 to recite “a degree of polymerization is 5 or more and 80 or less”, as Denka does not teach or suggest a reagent with a degree of polymerization is 5 or more and 80 or less.
Claims 1 and 3-11 are rejected under 35 U.S.C. 103 as being unpatentable over Denka in view of US 2020/0318155 (cited on the IDS filed 01/12/2024; herein Denka2) and Capek et al. (Adv Colloid Interface Sci, 2000, 88:295; cited on the attached Form PTO-892; herein Capek).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 1 (claims 3-8 dependent therefrom) is drawn to a reagent composition kit for quantifying small dense LDL cholesterol (sdLDL-C) in sample comprising
a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and
a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein,
wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and
a degree of polymerization in the first reagent is 5 or more or 80 or less.
Claim 9 is drawn to a reagent kit composition for quantifying sdLDL-C in a sample comprising
a first reagent composition containing POE-MS-PE, the first reagent configured to act on the sample; and
a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein,
wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and
a degree of polymerization in the first reagent is 11 or more or 33 or less.
Claim 10 is drawn to a reagent kit composition for quantifying sdLDL-C in a sample comprising
a first reagent composition containing POE-MS-PE, the first reagent configured to act on the sample; and
a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein,
wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and
a degree of polymerization in the first reagent is 13 or more or 37 or less.
Claim 11 is drawn to a reagent kit composition for quantifying sdLDL-C in a sample comprising
a first reagent composition containing POE-MS-PE, the first reagent configured to act on the sample; and
a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein,
wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and
a degree of polymerization in the first reagent is 50 or more or 80 or less.
In view of the indefiniteness of the claims stated above, and for the sake of compact prosecution, the limitations regarding degree of polymerization recited in the claims are being interpreted as corresponding to the polyoxyethylene of the POE-MS-PE component of the first reaction composition.
Regarding the limitations of “configured to act on the sample” and “configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein” recited in claims 1 and 9-11, in view of the claim interpretation under 112(f) and the indefiniteness described above, these limitations are considered to be functional limitations drawn to the intended use of the kit components and do not structurally limit the reaction composition kit, the first reaction composition or the second reaction composition (see MPEP 2111.02).
Denka relates to reagents for quantitative determination of sdLDLs [title], and discusses methods for quantitatively determining sdLDL-C in samples [abstract].
Regarding claims 1 and 9-11, Denka teaches a reagent for the quantitative determination of small dense LDLs [title] used in a method for determining cholesterol comprising a step of eliminating lipoproteins other than sdLDLs in a sample in the presence of cholesterol esterase and a surfactant that acts on lipoproteins other than sdLDLs, and a step of quantitatively determining cholesterol in sdLDLs that remain after the removal step [abstract], which corresponds to a first reagent composition comprising a surfactant and cholesterol esterase, and a second reagent composition comprising components to quantify the remaining sdLDL-C.
Denka does not teach the first reagent composition contains POE-MS-PE, and has a degree of polymerization of 5 or more and 80 or less.
Denka2 relates to methods and reagents for quantifying cholesterol in lipoprotein [title], and discusses method steps to eliminate specific cholesterols in a sample by interacting the sample with cholesterol esterase and a surfactant [abstract].
Regarding claims 1 and 9-11, Denka2 teaches the surfactant comprises polyoxyethylene styrenated phenyl ether [para 0017], which is considered to correspond to POE-MS-PE recited in the claims.
Capek relates to surface active properties of polyoxyethylene macromonomers [title] and discusses the organized structure of micelles and their effect on polymerization and subsequent surface-active compounds, as well as the colloidal stability of certain polymers [abstract].
Regarding claims 1 and 9-11, Capek teaches that polymacronomers, such as polyoxyethylene, comprising both polymeric and monomeric molecules in aqueous solution behave in such a way where amphiphilic molecules try to minimize the contact area of hydrophobic groups with water molecules, wherein the aggregation number of micelles in monomeric molecules is determined by equilibrium thermodynamics, but polymeric molecules contain topological constraints [p 313, final para]. Capek teaches that if the degree of polymerization of polymacronomers exceeds the aggregation number of the monomer micelle, unsaturated sites of the molecules become available and intermolecular actions occur [p 314, first para]. While Capek does not teach a degree of polymerization corresponding to POE of 5 or more and 80 or less (corresponding to claim 1), 11 or more and 33 or less (corresponding to claim 9), 13 or more and 37 or less (corresponding to claim 10), and 50 or more and 80 or less (corresponding to claim 11), Capek teaches that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. Therefore one of skill in the art would have been motivated to modify the POE-MS-PE of Denka2 to achieve the degree of polymerizations recited by the claims, because Denka and Denka2 teach the use of surfactant to eliminate unwanted cholesterol, Denka2 teaches POE-MS-PE is the surfactant, and Capek teaches that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka and Denka 2, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the first reagent composition of Denka by replacing the surfactant with the POE-MS-PE of Denka 2, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the surfactant of Denka and the POE-MS-PE of Denka2 are both surfactants used in the elimination of lipoproteins, and as such both are capable of being incorporated into reagent compositions such as those disclosed by Denka. Thus it would have been obvious to one of ordinary skill in the art to replace the surfactant of Denka with the POE-MS-PE of Denka2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Denka and Denka2 relate to methods of quantifying cholesterol comprising steps of eliminating unwanted lipoproteins by interacting with a surfactant.
In view of Denka, Denka2 and Capek, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of Denka and Denka2 by altering the degree of polymerization of the POE-MS-PE to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to alter the degree of polymerization of the POE-MS-PE because Capek teaches that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. One of ordinary skill in the art would have had a reasonable expectation of success because Denka and Denka2 teach the use of surfactant to eliminate unwanted lipoproteins, Denka2 teaches POE-MS-PE is the surfactant, and Capek teaches that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka, Denka2 and Capek, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of Denka, Denka2 and Capek by incorporating the components into a kit to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the reagent compositions into a kit because it is routine in the art to optimize methods for reproducibility, which includes the incorporation of necessary components into a kit.
Regarding claim 3, the phrase “the reagent composition” is being interpreted as corresponding to the first reagent composition recited in claim 1 in view of the indefiniteness described above. Additionally, the phrase “an entire reagent composition” in the limitation “a content of the POE-MS-PE in the reagent composition is 0.05% (w/v) or more and 0.6% (w/v) or less with respect to an entire reagent composition” is broadly but reasonably considered to encompass any reagent composition. Denka2 teaches the concentration of surfactant is preferably from 0.05% to 5% [para 0037], wherein the percentages are considered to correspond to %(w/v) with respect to an entire reagent composition as recited in the claim. According to MPEP 2144.05.I, where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding claim 4, Denka2 teaches the reagent composition may further contain catalase [para 0046].
Regarding claim 5, Denka2 teaches the reagent composition may contain a hydrogen donor such as aniline [para 0046].
Regarding claim 6, the claim is rejected under 35 USC 112(d) as not further limiting the reagent composition kit of claim 1, and therefore the rejection of claim 6 is included in the rejection of claim 1 above.
Regarding claim 7, Denka teaches a first and second reagent composition in example 2, wherein the second reagent composition comprises peroxidase [para 0053].
Regarding claim 8, Denka teaches a first and second reagent composition in example 2, wherein the first reagent composition comprises TOOS [para 0052] which is an aniline derivative that acts as a hydrogen donor [para 0035], and the second reagent composition comprises 4-aminoantipyrine [para 0053] which is understood to be a coupler [see Specification para 0055].
Therefore, the invention of claims 1 and 3-11 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on page 11 of Applicant’s response to rejections under 35 USC 102 and 35 USC 103; Applicant in summary contends Denka does not teach POE-MS-PE or a degree of polymerization of 5 or more or 80 or less as recited by amended claim 1, and as such does not anticipate nor render obvious the claimed invention.
Applicant’s remarks are considered and found not convincing. While the rejections under 35 USC 102 and 35 USC 103 over Denka have been withdrawn as a result of Applicant’s instant amendments to claim 1, the amendments have raised new grounds of rejection under 35 USC 103 as stated above as being unpatentable over Denka in view of Denka 2 and Capek.
Double Patenting
The double patenting and provisional double patenting rejections A.-E. set forth in the office action mailed 11/21/2025 at pp. 19-30 are withdrawn in view of the instant claim amendments.
A. Claims 1 and 3-11 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,209,270 (cited on the Form PTO-892 mailed 11/21/2025; herein “patent”) in view of Denka, Denka2 and Capek.
The instant rejection is newly stated and necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the patent recites a kit to fractionate sdLDL-C comprising a first reagent composition.
The claims of the patent do not recite a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and a degree of polymerization in the first reagent is 5 or more or 80 or less.
Denka relates to reagents for quantitative determination of sdLDLs [title], and discusses methods for quantitatively determining sdLDL-C in samples [abstract].
Regarding instant claims 1 and 9-11, Denka discloses a reagent for the quantitative determination of small dense LDLs [title] used in a method for determining cholesterol comprising a step of eliminating lipoproteins other than sdLDLs in a sample in the presence of cholesterol esterase and a surfactant that acts on lipoproteins other than sdLDLs, and a step of quantitatively determining cholesterol in sdLDLs that remain after the removal step [abstract], which corresponds to a first reagent composition comprising a surfactant and cholesterol esterase, and a second reagent composition comprising components to quantify the remaining sdLDL-C.
Regarding instant claims 1 and 9-11, Denka2 discloses the surfactant comprises polyoxyethylene styrenated phenyl ether [para 0017], which is considered to correspond to POE-MS-PE recited in the claims.
Capek relates to surface active properties of polyoxyethylene macromonomers [title] and discusses the organized structure of micelles and their effect on polymerization and subsequent surface-active compounds, as well as the colloidal stability of certain polymers [abstract].
Regarding instant claims 1 and 9-11, Capek discloses that polymacronomers, such as polyoxyethylene, comprising both polymeric and monomeric molecules in aqueous solution behave in such a way where amphiphilic molecules try to minimize the contact area of hydrophobic groups with water molecules, wherein the aggregation number of micelles in monomeric molecules is determined by equilibrium thermodynamics, but polymeric molecules contain topological constraints [p 313, final para]. Capek discloses that if the degree of polymerization of polymacronomers exceeds the aggregation number of the monomer micelle, unsaturated sites of the molecules become available and intermolecular actions occur [p 314, first para]. While Capek does not disclose a degree of polymerization corresponding to POE of 5 or more and 80 or less (corresponding to instant claim 1), 11 or more and 33 or less (corresponding to instant claim 9), 13 or more and 37 or less (corresponding to instant claim 10), and 50 or more and 80 or less (corresponding to instant claim 11), Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. Therefore one of skill in the art would have been motivated to modify the POE-MS-PE of Denka2 to achieve the degree of polymerizations recited by the claims, because the patent recites a kit to fractionate sdLDL-C, Denka and Denka2 disclose a surfactant to eliminate unwanted lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by including the reagent compositions of Denka to arrive at the claimed invention. One of ordinary skill in the art would been motivated to modify the claims of the patent because Denka discloses a methods of eliminating target lipoproteins by interacting with surfactant and cholesterol esterase from a sample to isolate sdLDL-C. One or ordinary skill in the art would have had a reasonable expectation of success because the patent and Denka relate to isolating or fractionating sdLDL-C.
In view of the Denka and Denka2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined first reagent composition of the patent and Denka by replacing the surfactant of Denka with the POE-MS-PE of Denka 2, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the surfactant of Denka and the POE-MS-PE of Denka2 are both surfactants used in the elimination of lipoproteins, and as such both are capable of being incorporated into reagent compositions such as those disclosed by Denka and the patent. Thus it would have been obvious to one of ordinary skill in the art to replace the surfactant of Denka with the POE-MS-PE of Denka2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Denka and Denka2 relate to methods of quantifying cholesterol comprising steps of eliminating unwanted lipoproteins by interacting with a surfactant.
In view of Denka, Denka2 and Capek, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of the patent, Denka and Denka2 by altering the degree of polymerization of the POE-MS-PE to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to alter the degree of polymerization of the POE-MS-PE because Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. One of ordinary skill in the art would have had a reasonable expectation of success because the patent, Denka and Denka2 relate to a composition for isolating targeted lipoproteins, Denka and Denka2 relate to the use of a surfactant to isolate a target lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
Regarding instant claim 3, the phrase “the reagent composition” is being interpreted as corresponding to the first reagent composition recited in claim 1 in view of the indefiniteness described above. Additionally, the phrase “an entire reagent composition” in the limitation “a content of the POE-MS-PE in the reagent composition is 0.05% (w/v) or more and 0.6% (w/v) or less with respect to an entire reagent composition” is broadly but reasonably considered to encompass any reagent composition. Denka2 discloses the concentration of surfactant is preferably from 0.05% to 5% [para 0037], wherein the percentages are considered to correspond to %(w/v) with respect to an entire reagent composition as recited in the claim. According to MPEP 2144.05.I, where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding instant claim 4, Denka2 discloses the reagent composition may further contain catalase [para 0046].
Regarding instant claim 5, Denka2 discloses the reagent composition may contain a hydrogen donor such as aniline [para 0046].
Regarding instant claim 6, the instant claim is rejected under 35 USC 112(d) as not further limiting the reagent composition kit of instant claim 1, and therefore the rejection of instant claim 6 is included in the rejection of instant claim 1 above.
Regarding instant claim 7, Denka discloses a first and second reagent composition in example 2, wherein the second reagent composition comprises peroxidase [para 0053].
Regarding instant claim 8, Denka discloses a first and second reagent composition in example 2, wherein the first reagent composition comprises TOOS [para 0052] which is an aniline derivative that acts as a hydrogen donor [para 0035], and the second reagent composition comprises 4-aminoantipyrine [para 0053] which is understood to be a coupler [see Specification para 0055].
B. Claims 1 and 3-11 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application 17/641689 (herein “reference application”) in view of Denka, Denka2 and Capek.
The instant rejection is newly stated and necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the reference application recites a kit to quantify sdLDL-C comprising a first reagent composition.
The claims of the reference application do not recite a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and a degree of polymerization in the first reagent is 5 or more or 80 or less.
Denka relates to reagents for quantitative determination of sdLDLs [title], and discusses methods for quantitatively determining sdLDL-C in samples [abstract].
Regarding instant claims 1 and 9-11, Denka discloses a reagent for the quantitative determination of small dense LDLs [title] used in a method for determining cholesterol comprising a step of eliminating lipoproteins other than sdLDLs in a sample in the presence of cholesterol esterase and a surfactant that acts on lipoproteins other than sdLDLs, and a step of quantitatively determining cholesterol in sdLDLs that remain after the removal step [abstract], which corresponds to a first reagent composition comprising a surfactant and cholesterol esterase, and a second reagent composition comprising components to quantify the remaining sdLDL-C.
Regarding instant claims 1 and 9-11, Denka2 discloses the surfactant comprises polyoxyethylene styrenated phenyl ether [para 0017], which is considered to correspond to POE-MS-PE recited in the claims.
Capek relates to surface active properties of polyoxyethylene macromonomers [title] and discusses the organized structure of micelles and their effect on polymerization and subsequent surface-active compounds, as well as the colloidal stability of certain polymers [abstract].
Regarding instant claims 1 and 9-11, Capek discloses that polymacronomers, such as polyoxyethylene, comprising both polymeric and monomeric molecules in aqueous solution behave in such a way where amphiphilic molecules try to minimize the contact area of hydrophobic groups with water molecules, wherein the aggregation number of micelles in monomeric molecules is determined by equilibrium thermodynamics, but polymeric molecules contain topological constraints [p 313, final para]. Capek discloses that if the degree of polymerization of polymacronomers exceeds the aggregation number of the monomer micelle, unsaturated sites of the molecules become available and intermolecular actions occur [p 314, first para]. While Capek does not disclose a degree of polymerization corresponding to POE of 5 or more and 80 or less (corresponding to instant claim 1), 11 or more and 33 or less (corresponding to instant claim 9), 13 or more and 37 or less (corresponding to instant claim 10), and 50 or more and 80 or less (corresponding to instant claim 11), Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. Therefore one of skill in the art would have been motivated to modify the POE-MS-PE of Denka2 to achieve the degree of polymerizations recited by the claims, because the reference application recites a kit to fractionate sdLDL-C, Denka and Denka2 disclose a surfactant to eliminate unwanted lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by including the reagent compositions of Denka to arrive at the claimed invention. One of ordinary skill in the art would been motivated to modify the claims of the reference application because Denka discloses a method of quantifying sdLDL-C eliminating target lipoproteins by interacting with surfactant and cholesterol esterase from a sample to isolate sdLDL-C. One or ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to isolating or fractionating sdLDL-C.
In view of the Denka and Denka2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined first reagent composition of the reference application and Denka by replacing the surfactant of Denka with the POE-MS-PE of Denka 2, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the surfactant of Denka and the POE-MS-PE of Denka2 are both surfactants used in the elimination of lipoproteins, and as such both are capable of being incorporated into reagent compositions such as those disclosed by Denka and the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace the surfactant of Denka with the POE-MS-PE of Denka2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Denka and Denka2 relate to methods of quantifying cholesterol comprising steps of eliminating unwanted lipoproteins by interacting with a surfactant.
In view of Denka, Denka2 and Capek, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of the reference application, Denka and Denka2 by altering the degree of polymerization of the POE-MS-PE to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to alter the degree of polymerization of the POE-MS-PE because Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to a composition for quantifying sdLDL-C, Denka and Denka2 relate to the use of a surfactant to isolate a target lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
Regarding instant claim 3, the phrase “the reagent composition” is being interpreted as corresponding to the first reagent composition recited in claim 1 in view of the indefiniteness described above. Additionally, the phrase “an entire reagent composition” in the limitation “a content of the POE-MS-PE in the reagent composition is 0.05% (w/v) or more and 0.6% (w/v) or less with respect to an entire reagent composition” is broadly but reasonably considered to encompass any reagent composition. Denka2 discloses the concentration of surfactant is preferably from 0.05% to 5% [para 0037], wherein the percentages are considered to correspond to %(w/v) with respect to an entire reagent composition as recited in the claim. According to MPEP 2144.05.I, where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding instant claim 4, Denka2 discloses the reagent composition may further contain catalase [para 0046].
Regarding instant claim 5, Denka2 discloses the reagent composition may contain a hydrogen donor such as aniline [para 0046].
Regarding instant claim 6, the instant claim is rejected under 35 USC 112(d) as not further limiting the reagent composition kit of instant claim 1, and therefore the rejection of instant claim 6 is included in the rejection of instant claim 1 above.
Regarding instant claim 7, Denka discloses a first and second reagent composition in example 2, wherein the second reagent composition comprises peroxidase [para 0053].
Regarding instant claim 8, Denka discloses a first and second reagent composition in example 2, wherein the first reagent composition comprises TOOS [para 0052] which is an aniline derivative that acts as a hydrogen donor [para 0035], and the second reagent composition comprises 4-aminoantipyrine [para 0053] which is understood to be a coupler [see Specification para 0055].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
C. Claims 1 and 3-11 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application 18/007689 (herein “reference application”) in view of Denka, Denka2 and Capek.
The instant rejection is newly stated and necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the reference application recites a kit to quantify cholesterol comprising a first reagent composition.
The claims of the reference application do not recite a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and a degree of polymerization in the first reagent is 5 or more or 80 or less.
Denka relates to reagents for quantitative determination of sdLDLs [title], and discusses methods for quantitatively determining sdLDL-C in samples [abstract].
Regarding instant claims 1 and 9-11, Denka discloses a reagent for the quantitative determination of small dense LDLs [title] used in a method for determining cholesterol comprising a step of eliminating lipoproteins other than sdLDLs in a sample in the presence of cholesterol esterase and a surfactant that acts on lipoproteins other than sdLDLs, and a step of quantitatively determining cholesterol in sdLDLs that remain after the removal step [abstract], which corresponds to a first reagent composition comprising a surfactant and cholesterol esterase, and a second reagent composition comprising components to quantify the remaining sdLDL-C.
Regarding instant claims 1 and 9-11, Denka2 discloses the surfactant comprises polyoxyethylene styrenated phenyl ether [para 0017], which is considered to correspond to POE-MS-PE recited in the claims.
Capek relates to surface active properties of polyoxyethylene macromonomers [title] and discusses the organized structure of micelles and their effect on polymerization and subsequent surface-active compounds, as well as the colloidal stability of certain polymers [abstract].
Regarding instant claims 1 and 9-11, Capek discloses that polymacronomers, such as polyoxyethylene, comprising both polymeric and monomeric molecules in aqueous solution behave in such a way where amphiphilic molecules try to minimize the contact area of hydrophobic groups with water molecules, wherein the aggregation number of micelles in monomeric molecules is determined by equilibrium thermodynamics, but polymeric molecules contain topological constraints [p 313, final para]. Capek discloses that if the degree of polymerization of polymacronomers exceeds the aggregation number of the monomer micelle, unsaturated sites of the molecules become available and intermolecular actions occur [p 314, first para]. While Capek does not disclose a degree of polymerization corresponding to POE of 5 or more and 80 or less (corresponding to instant claim 1), 11 or more and 33 or less (corresponding to instant claim 9), 13 or more and 37 or less (corresponding to instant claim 10), and 50 or more and 80 or less (corresponding to instant claim 11), Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. Therefore one of skill in the art would have been motivated to modify the POE-MS-PE of Denka2 to achieve the degree of polymerizations recited by the claims, because the reference application recites a kit to fractionate sdLDL-C, Denka and Denka2 disclose a surfactant to eliminate unwanted lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by including the reagent compositions of Denka to arrive at the claimed invention. One of ordinary skill in the art would been motivated to modify the claims of the reference application because Denka discloses a method of quantifying sdLDL-C eliminating target lipoproteins by interacting with surfactant and cholesterol esterase from a sample to isolate sdLDL-C. One or ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to isolating or fractionating sdLDL-C.
In view of the Denka and Denka2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined first reagent composition of the reference application and Denka by replacing the surfactant of Denka with the POE-MS-PE of Denka 2, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the surfactant of Denka and the POE-MS-PE of Denka2 are both surfactants used in the elimination of lipoproteins, and as such both are capable of being incorporated into reagent compositions such as those disclosed by Denka and the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace the surfactant of Denka with the POE-MS-PE of Denka2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Denka and Denka2 relate to methods of quantifying cholesterol comprising steps of eliminating unwanted lipoproteins by interacting with a surfactant.
In view of Denka, Denka2 and Capek, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of the reference application, Denka and Denka2 by altering the degree of polymerization of the POE-MS-PE to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to alter the degree of polymerization of the POE-MS-PE because Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to a composition for quantifying sdLDL-C, Denka and Denka2 relate to the use of a surfactant to isolate a target lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
Regarding instant claim 3, the phrase “the reagent composition” is being interpreted as corresponding to the first reagent composition recited in claim 1 in view of the indefiniteness described above. Additionally, the phrase “an entire reagent composition” in the limitation “a content of the POE-MS-PE in the reagent composition is 0.05% (w/v) or more and 0.6% (w/v) or less with respect to an entire reagent composition” is broadly but reasonably considered to encompass any reagent composition. Denka2 discloses the concentration of surfactant is preferably from 0.05% to 5% [para 0037], wherein the percentages are considered to correspond to %(w/v) with respect to an entire reagent composition as recited in the claim. According to MPEP 2144.05.I, where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding instant claim 4, Denka2 discloses the reagent composition may further contain catalase [para 0046].
Regarding instant claim 5, Denka2 discloses the reagent composition may contain a hydrogen donor such as aniline [para 0046].
Regarding instant claim 6, the instant claim is rejected under 35 USC 112(d) as not further limiting the reagent composition kit of instant claim 1, and therefore the rejection of instant claim 6 is included in the rejection of instant claim 1 above.
Regarding instant claim 7, Denka discloses a first and second reagent composition in example 2, wherein the second reagent composition comprises peroxidase [para 0053].
Regarding instant claim 8, Denka discloses a first and second reagent composition in example 2, wherein the first reagent composition comprises TOOS [para 0052] which is an aniline derivative that acts as a hydrogen donor [para 0035], and the second reagent composition comprises 4-aminoantipyrine [para 0053] which is understood to be a coupler [see Specification para 0055].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
D. Claims 1 and 3-11 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application 18/855879 (herein “reference application”) in view of Denka, Denka2 and Capek.
The instant rejection is newly stated and necessitated by claim amendment.
Regarding instant claim 1, claim 1 of the reference application recites a first reagent composition.
The claims of the reference application do not recite a first reagent composition containing polyoxyethylene monostyrenated phenyl ether (POE-MS-PE), the first reagent configured to act on the sample; and a second reagent composition configured to quantify sdLDL-C to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition has one, two, or three activities selected from the group consisting of cholesterol esterase activity, cholesterol oxidase activity, and sphingomyelinase activity, and a degree of polymerization in the first reagent is 5 or more or 80 or less.
Denka relates to reagents for quantitative determination of sdLDLs [title], and discusses methods for quantitatively determining sdLDL-C in samples [abstract].
Regarding instant claims 1 and 9-11, Denka discloses a reagent for the quantitative determination of small dense LDLs [title] used in a method for determining cholesterol comprising a step of eliminating lipoproteins other than sdLDLs in a sample in the presence of cholesterol esterase and a surfactant that acts on lipoproteins other than sdLDLs, and a step of quantitatively determining cholesterol in sdLDLs that remain after the removal step [abstract], which corresponds to a first reagent composition comprising a surfactant and cholesterol esterase, and a second reagent composition comprising components to quantify the remaining sdLDL-C.
Regarding instant claims 1 and 9-11, Denka2 discloses the surfactant comprises polyoxyethylene styrenated phenyl ether [para 0017], which is considered to correspond to POE-MS-PE recited in the claims.
Capek relates to surface active properties of polyoxyethylene macromonomers [title] and discusses the organized structure of micelles and their effect on polymerization and subsequent surface-active compounds, as well as the colloidal stability of certain polymers [abstract].
Regarding instant claims 1 and 9-11, Capek discloses that polymacronomers, such as polyoxyethylene, comprising both polymeric and monomeric molecules in aqueous solution behave in such a way where amphiphilic molecules try to minimize the contact area of hydrophobic groups with water molecules, wherein the aggregation number of micelles in monomeric molecules is determined by equilibrium thermodynamics, but polymeric molecules contain topological constraints [p 313, final para]. Capek discloses that if the degree of polymerization of polymacronomers exceeds the aggregation number of the monomer micelle, unsaturated sites of the molecules become available and intermolecular actions occur [p 314, first para]. While Capek does not disclose a degree of polymerization corresponding to POE of 5 or more and 80 or less (corresponding to instant claim 1), 11 or more and 33 or less (corresponding to instant claim 9), 13 or more and 37 or less (corresponding to instant claim 10), and 50 or more and 80 or less (corresponding to instant claim 11), Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. Therefore one of skill in the art would have been motivated to modify the POE-MS-PE of Denka2 to achieve the degree of polymerizations recited by the claims, because the reference application recites a kit to fractionate sdLDL-C, Denka and Denka2 disclose a surfactant to eliminate unwanted lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
In view of Denka, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by including the reagent compositions of Denka to arrive at the claimed invention. One of ordinary skill in the art would been motivated to modify the claims of the reference application because Denka discloses a method of quantifying sdLDL-C eliminating target lipoproteins by interacting with surfactant and cholesterol esterase from a sample to isolate sdLDL-C. One or ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to isolating or fractionating sdLDL-C.
In view of the Denka and Denka2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined first reagent composition of the reference application and Denka by replacing the surfactant of Denka with the POE-MS-PE of Denka 2, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the surfactant of Denka and the POE-MS-PE of Denka2 are both surfactants used in the elimination of lipoproteins, and as such both are capable of being incorporated into reagent compositions such as those disclosed by Denka and the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace the surfactant of Denka with the POE-MS-PE of Denka2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Denka and Denka2 relate to methods of quantifying cholesterol comprising steps of eliminating unwanted lipoproteins by interacting with a surfactant.
In view of Denka, Denka2 and Capek, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined reagent composition of the reference application, Denka and Denka2 by altering the degree of polymerization of the POE-MS-PE to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to alter the degree of polymerization of the POE-MS-PE because Capek discloses that degree of polymerization is a result effective variable according to MPEP 2144.05.II.B, which is a variable that achieves a recognizable result of controlling intermolecular interactions. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application and Denka relate to a reaction compositions, Denka and Denka2 relate to the use of a surfactant to isolate a target lipoprotein, Denka2 discloses POE-MS-PE is the surfactant, and Capek discloses that the degree of intermolecular interactions by POE polymacronomers can be controlled through its degree of polymerization.
Regarding instant claim 3, the phrase “the reagent composition” is being interpreted as corresponding to the first reagent composition recited in claim 1 in view of the indefiniteness described above. Additionally, the phrase “an entire reagent composition” in the limitation “a content of the POE-MS-PE in the reagent composition is 0.05% (w/v) or more and 0.6% (w/v) or less with respect to an entire reagent composition” is broadly but reasonably considered to encompass any reagent composition. Denka2 discloses the concentration of surfactant is preferably from 0.05% to 5% [para 0037], wherein the percentages are considered to correspond to %(w/v) with respect to an entire reagent composition as recited in the claim. According to MPEP 2144.05.I, where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding instant claim 4, Denka2 discloses the reagent composition may further contain catalase [para 0046].
Regarding instant claim 5, Denka2 discloses the reagent composition may contain a hydrogen donor such as aniline [para 0046].
Regarding instant claim 6, the instant claim is rejected under 35 USC 112(d) as not further limiting the reagent composition kit of instant claim 1, and therefore the rejection of instant claim 6 is included in the rejection of instant claim 1 above.
Regarding instant claim 7, Denka discloses a first and second reagent composition in example 2, wherein the second reagent composition comprises peroxidase [para 0053].
Regarding instant claim 8, Denka discloses a first and second reagent composition in example 2, wherein the first reagent composition comprises TOOS [para 0052] which is an aniline derivative that acts as a hydrogen donor [para 0035], and the second reagent composition comprises 4-aminoantipyrine [para 0053] which is understood to be a coupler [see Specification para 0055].
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks: Beginning on page 13 of Applicant’s response to double patenting rejections; Applicant traverses the provisional rejections over applications 18/007,690, 18/007,689, and 18/855,879 as these are later filed applications and should be withdrawn according to MPEP 804.I.B.1.b.i; Applicant further contends the remaining double patenting rejections should be withdrawn in view of the instant claim amendments.
Applicant’s remarks are considered and found not convincing. Regarding MPEP 804.I.B.1.b.i, this relates to the standing of provisional double patenting rejections at the time of allowance when the only rejections remaining are the provisional double patenting rejections. In view of the instant claim amendments, the double patenting and provisional double patenting rejections set forth in the previous office action have been withdrawn, and new grounds of rejection have been made based on claim amendments as stated above.
Conclusion
Status of the Application:
Claims 1 and 3-11 are pending.
Claims 1 and 3-11 are rejected.
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
Prosecution Insights