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 .
Status of the Claims
Claims 124-129 and 131-143 are pending in this application. Claims 1-123 and 130 have been cancelled by applicant. Claims 124-129 and 133 are under examination herein. Claims 131-132 and 134-143 are withdrawn from consideration.
Claim Objections
Claims 124 and 127 are objected to because of the following informalities: The acronyms dNTP and NTP are not defined in the claims.
Claim 124 is also objected because Applicant left the “Formula 2” label from the deleted structure in the claim.
Appropriate correction is required.
Claim Interpretation
The terms dNTP and NTP are not defined in the claims and no definition appears to have been provided in the specification. From the art, these terms will be interpreted as “Deoxynucleotide Triphosphates” for dNTP, and “Nucleotide Triphosphates” for NTP.
Claim Rejections - 35 USC § 112
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.
Claim 127 is 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.
Claim 127 is rejected for lacking definitions for R1, R2, and n. The metes and bounds of this independent claim are unclear. For the purpose of applying art, it will be assumed that R1 and R-2 can independently be H or a metal ion.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 125-126 and 128 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 125-126 are rejected for failing to further limit claim 124, from which they depend. Claim 124 limits R1 to H, R2 to a metal ion, and R3 to substituted or unsubstituted aryl. Claims 125 and 126 expand this limitation to encompass R1 or R2 being H or aryl; and R3 being aryl or cycloalkyl.
Claim 128 also fails to further limit claim 124. Claim 124 speaks to the compound of Formula I wherein R2 is always a metal ion and always appears n times. Claim 128 does not limit this any further and simply reinstates that R2 comprises a metal ion appearing n times.
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Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 124-128 are rejected under 35 U.S.C. 103 as being unpatentable over Ahmad et al. (Biosci. Biotechnol. Biochem., 2007, 71, 1970–1978) (“Ahmad”); in view of Nielsen et al. (Journal of Chemical and Engineering Data, 1964, 9, 167-170) (“Nielsen”).
Regarding claims 124-128, Ahmed teaches all the chemicals used to prepare real time polymerase chain reaction (PCR) buffers are Tris-HCl buffer, MgCl2, dNTPs, and Taq polymerase (page 1971, Materials and Methods – section). Ahmed teaches that Tris-H3PO4 buffer (pH of 8.3) gave an expanded dynamic range for the detection of nucleic acids compared to Tris-HCl (abstract and page 1974, col. 1, last para.).
While Ahmed does not teach the instantly claimed phosphoric acids; the teachings of Nielsen are relied upon for these disclosures.
Nielsen teaches phenyl phosphoric acid and disodium phenyl phosphate (page 167, 7 and 8 lines from bottom) in water solutions.
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to put together a kit for routine PCR techniques comprising a polymerase, a dNTP, and a solution of a phosphoric acid of Formula 1, in view of Ahmed and Nielsen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Ahmed teaches the chemicals used to prepare PCR buffers, such as a Tris-HCl buffer, MgCl2, dNTPs, and Taq polymerase; further because Ahmed specifically teaches that phosphate titrated Tris buffers have an expanded dynamic range for the detection of nucleic acids compared to Tris-HCl; and further in view of Nielsen’s disclosure of phenyl phosphoric acid in an aqueous solution, which one of ordinary skill would have a reasonable expectation of success in using for titration of Tris to make the corresponding buffer, in view of Ahmed and Nielsen.
Further regarding the instant compounds of Formula 1, wherein R1 is H and R2 is a metal ion; while Nielsen’s phenyl phosphoric acid is not a monobasic phosphoric acid, as instant formula 1, Applicant is advised that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph). In the present case, Applicant would be required to show an unprecedented property of the instantly claimed monobasic phenyl phosphoric acid or an unexpected result that is not achieved with Ahmed’s phenyl phosphoric acid.
Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)). Therefore, Ahmed’s buffer components in view of Nielsen’s phosphoric acid, renders the instant claims to a kit comprising a polymerase, a dNTP, and monobasic phenyl phosphoric acid obvious.
Applicant is further advised that the preamble of the instant claims recite a “kit.” The specification, however, describes the kit as merely containing individually packed, known reagents, for use in nucleic acid molecule extensions (pages 18-22). The specification does not define this term “kit” further, and so it is being interpreted to encompass any collection of the compound of Formula 1, a polymerase, and a dNTP, as indicated in the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. See MPEP § 2112.01 I-III. Applicant is advised that products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Regarding claim 127, the compounds of Formula 1-2 correspond to alkyl substituted phenyl phosphoric acids, such as methyl-phenyl phosphoric acid (wherein n = 1, x = 1, and z = 3). Applicant is advised that R1 and R2 have not been defined in this independent claim, and therefore, R1-2 have been assumed to both be H (see 112(b)). While Nielsen doesn’t specifically disclose methyl-phenyl phosphoric acid, Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
Therefore, the instant kit comprising methyl-phenyl phosphoric acid, a polymerase, and a dNTP is prima facie obvious in view of the teachings from Ahmed and Nielsen, as outlined above.
Claims 124-126 and 128-129 are rejected under 35 U.S.C. 103 as being unpatentable over Ahmad et al. (Biosci. Biotechnol. Biochem., 2007, 71, 1970–1978) (“Ahmad”); in view of Heilmann et al. (Chem. Eur. J. 2019, 25, 12900 – 12904) (“Heilmann”).
Regarding claims 124-126 and 128-129, Ahmed teaches all the chemicals used to prepare real time polymerase chain reaction (PCR) buffers are Tris-HCl buffer, MgCl2, dNTPs, and Taq polymerase (page 1971, Materials and Methods – section). Ahmed teaches that Tris-H3PO4 buffer (pH of 8.3) gave an expanded dynamic range for the detection of nucleic acids compared to Tris-HCl (abstract and page 1974, col. 1, last para.).
While Ahmed does not teach the instantly claimed phosphoric acids; the teachings of Heilmann are relied upon for these disclosures.
Heilmann discloses phenylene-diphosphoric acid below, in a buffered aqueous solution which reads on the instant compounds of Formula 1 when n = 2 (reading on instant claim 129) (Table 1, page 12902; and page 12903, lines bridging col. 1-2).
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to put together a kit for routine PCR techniques comprising a polymerase, a dNTP, and a solution of a phosphoric acid of Formula 1 (with n = 2), in view of Ahmed and Heilmann. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Ahmed teaches the chemicals used to prepare PCR buffers, such as a Tris-HCl buffer, MgCl2, dNTPs, and Taq polymerase; further because Ahmed specifically teaches that phosphate titrated Tris buffers have an expanded dynamic range for the detection of nucleic acids compared to Tris-HCl; and further in view of Heilmann’s disclosure of phenylene-diphosphoric acid in an aqueous buffered solution, which one of ordinary skill would have a reasonable expectation of success in using for titration of Tris to make the corresponding buffer, in view of Ahmed and Heilmann.
Further regarding the instant compounds of Formula 1, wherein R1 is H and R2 is a metal ion; while Heilmann’s phenylene-diphosphoric acid is not a monobasic phosphoric acid, as instant formula 1, Applicant is reminded that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on”. In the present case, Applicant would be required to show an unprecedented property of the instantly claimed monobasic phenylene-diphosphoric acid or an unexpected result that is not achieved with Ahmed’s phenyl phosphoric acid.
Applicant is reminded that similar properties may normally be presumed when compounds are very close in structure. (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Therefore, Ahmed’s buffer components in view of Heilmann’s phosphoric acid, renders the instant claims to a kit comprising a polymerase, a dNTP, and monobasic phenyl phosphoric acid obvious.
Applicant is reminded that the preamble of the instant claims recite a “kit.” The specification, however, describes the kit as merely containing individually packed, known reagents, for use in nucleic acid molecule extensions (pages 18-22). The specification does not define this term “kit” further, and so it is being interpreted to encompass any collection of the compound of Formula 1, a polymerase, and a dNTP, as indicated in the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. Applicant is reminded that products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Claim 133 is rejected under 35 U.S.C. 103 as being unpatentable over Ahmad et al. (Biosci. Biotechnol. Biochem., 2007, 71, 1970–1978) (“Ahmad”); in view of Nielsen et al. (Journal of Chemical and Engineering Data, 1964, 9, 167-170) (“Nielsen”); as applied to claims 124-128; further in view of Fadanka et al. (Obtained from protocols.io [retrieved on September 27th, 2025] <URL: https://www.protocols.io/view/preparation-of-pbs-solution-3byl4bxjrvo5/v1?u=%2Fview%2Fpreparation-of-pbs-solution-3byl4bxjrvo5%2Fv1> - Published June 14th, 2022 – previously cited) (“Fadanka”).
The teachings of Ahmed and Nielsen are disclosed above and incorporated herein.
While Ahmed and Nielsen do not specifically disclose a phosphoric acid concentration of 1-150 µmol/L, the teachings of Fadanka are relied upon for these disclosures.
Fadanka discloses a protocol for the preparation of a phosphate buffered saline (PBS) solution, commonly used in biological research (page 1, para. 1, line 1). Fadanka discloses a sodium phosphate dibasic solution with an initial concentration of 10 mmol/ L and a potassium phosphate solution with an initial concentration of 1.8 mmol/ L (Table at the bottom of page 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a solution comprising Ahmed in view of Nielsen’s phosphate compounds in any concentration desired, including 1-150 µmol/ L. One of ordinary skill would have been motivated to do so in view of Ahmed in view of Nielsen’s disclosure of their phosphoric acid solutions for titration of a Tris base to make a buffer. One of ordinary skill would have had a reasonable expectation of success in view of Fadanka’s disclosure of a protocol for preparing PBS, which is a commonly used phosphate buffer, containing phosphates at about 1.8 to 11.8 mmol/ L. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR, 550 U.S. at 421, 82 USPQ2d at 1397.
Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 133 is rejected under 35 U.S.C. 103 as being unpatentable over Ahmad et al. (Biosci. Biotechnol. Biochem., 2007, 71, 1970–1978) (“Ahmad”); in view of Heilmann et al. (Chem. Eur. J. 2019, 25, 12900 – 12904) (“Heilmann”); as applied to claims 124-126 and 128-129; further in view of Fadanka et al. (Obtained from protocols.io [retrieved on September 27th, 2025] <URL: https://www.protocols.io/view/preparation-of-pbs-solution-3byl4bxjrvo5/v1?u=%2Fview%2Fpreparation-of-pbs-solution-3byl4bxjrvo5%2Fv1> - Published June 14th, 2022 – previously cited) (“Fadanka”).
The teachings of Ahmed and Heilmann are disclosed above and incorporated herein.
While Ahmed and Heilmann do not specifically disclose a phosphoric acid concentration of 1-150 µmol/L, the teachings of Fadanka are relied upon for these disclosures.
Fadanka discloses a protocol for the preparation of a phosphate buffered saline (PBS) solution, commonly used in biological research (page 1, para. 1, line 1). Fadanka discloses a sodium phosphate dibasic solution with an initial concentration of 10 mmol/ L and a potassium phosphate solution with an initial concentration of 1.8 mmol/ L (Table at the bottom of page 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a solution comprising Ahmed in view of Heilmann’s phosphate compounds in any concentration desired, including 1-150 µmol/ L. One of ordinary skill would have been motivated to do so in view of Ahmed in view of Heilmann’s disclosure of their phosphoric acid solutions for titration of a Tris base to make a buffer. One of ordinary skill would have had a reasonable expectation of success in view of Fadanka’s disclosure of a protocol for preparing PBS, which is a commonly used phosphate buffer, containing phosphates at about 1.8 to 11.8 mmol/ L. A person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been introduced.
Claim Objections
Applicant’s arguments, see page 7, filed 01/07/2026, with respect to objections to the claims have been fully considered and are persuasive. The objection of the claim has been withdrawn. However, upon further consideration, a new ground(s) of objection is made in view of amendments to claims 124 and 127.
Claim Rejections - 35 USC § 112(d)
Applicant’s arguments, see page 7, filed 01/07/2026, with respect to 35 USC § 112(d) rejections have been fully considered and are persuasive. The 35 USC § 112(d) rejections of the claims has been withdrawn. However, upon further consideration, a new ground(s) of 35 USC § 112(d) rejections is made in view of amendments to claims.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see page 7, filed 01/07/2026, with respect to 35 USC § 103 rejections have been fully considered and are persuasive. The 35 USC § 103 rejections of the claims has been withdrawn. However, upon further consideration, a new ground(s) of 35 USC § 103 rejections is made in view of amendments to claims.
Applicant states that the Fadanka reference does not cure the deficiencies of Liu.
The new ground of rejections presented herein does not rely on Liu for any teaching. New rejections were necessitated in view of Applicant’s amendments to the claims. This action is final.
Conclusion
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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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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