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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-13 and 27), in the reply filed on 27 April 2026, is acknowledged.
Applicants provided a compliant species election of:
“doxorubicin” as species of “anthracycline anticancer agent”; and
“5-aminolevulinic acid” as a species of “agent”.
Claims 1-13 and 27 read on the elected species.
Claims 14-26 and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention of Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 27 April 2026.
Current Status of 18/552,098
This Office Action is responsive to the amended claims of 22 September 2023.
Currently amended claims 1-13 and 27 have been examined on the merits.
Priority
The instant application’s effective filing date is 15 March 2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 19 May 2026; 18 June 2025; and 29 December 2023, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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.
Claims 9-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention
The term “preferably” (two occurrences) in claim 9 is a relative term which renders the claim 9 indefinite under 35 USC 112(b). The term “preferably” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, the metes and bounds of claim 9 are undefined and hence claim 9 is rejected under 35 USC 112(b) as indefinite.
Furthermore, “preferably” renders the metes and bounds of claim 9 undefined (hence rendering claim 9 indefinite under 35 USC 112(b)) since the artisan does not know if the limitations following “preferably” are merely exemplary or are required limitations of the claim.
Claim 10 is similarly rejected as indefinite under 35 USC 112(b) since it refers back to claim 9 but does not remedy the rationale underpinning the basis for rejecting claim 9.
Claim 9 contains limitations within parentheticals which renders the metes and bounds of claim 9 undefined (hence rendering claim 9 indefinite under 35 USC 112(b)) since the artisan does not know if the limitations within parentheticals are merely exemplary or are required limitations of the claim.
Claim 10 is similarly rejected as indefinite under 35 USC 112(b) since it refers back to claim 9 but does not remedy the rationale underpinning the basis for rejecting claim 9.
To render moot all these rejections: Please delete all parentheticals surrounding limitations in all the claims AND delete all occurrences of “prefer”, etc.
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 1-13 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.
The statute 35 USC 112(d) requires a dependent claim to reference a previously set forth claim and further limit it. If a dependent claim is misnumbered and appears earlier in the sequence than the independent claim it refers to, the claim numbering violates the 35 USC 112(d) statute and the numbering is rejected as invalid.
Here, claim 1 is a dependent claim that improperly refers to a later independent claim number (claim 27). Thus, claim 1 is rejected under 35 USC 112(d) since dependent claim 1 appears earlier in the sequence and cannot reference a previously set forth (emphasis) independent claim. See MPEP 608.01(n).
Claims 2-13 are similarly rejected under 35 USC 112(d) since these claims refer back to claim 1 but do not remedy the rationale underpinning the basis for rejecting claim 1.
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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-4, 11, 13, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
TSUKUBA (JP 2011-225471 A, Espacenet machine-generated English-language translation enclosed).
The prior art reference TSUKUBA teaches administering a pharmaceutical composition comprising 5-aminolevulinic acid (Applicants’ elected “Agent”) before the addition of doxorubicin (Applicants’ elected “anthracycline anticancer agent”) to a subject. This results in protecting normal cells from cytotoxicity of doxorubicin and is interpreted by the Examiner and the Written Opinion as a method to reduce cytotoxicity of normal cells towards doxorubicin (see TSUKUBA Example 1 para [0016] as reported by Written Opinion for PCT/JP2022/011540). This anticipates instant claims 1, 4, 11, 13, and 27 (anticipates “5-aminolevulinic acid administered separately from doxorubicin” per instant claim 27). This is interpreted as anticipating instant claim 3 when the cells affected are cardiac cells (cytotoxicity would depress cardiac cells’ function and elevate lipid peroxide levels). This anticipates instant claim 11’s structure of 5-aminolevulinic acid, wherein R1 and R2 are both hydrogen (H).
Furthermore, the pharmaceutical composition can be administered via oral administration (para [0013]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-13 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over:
TSUKUBA (JP 2011-225471 A, Espacenet machine-generated English-language translation enclosed),
in view of:
SBI (WO 2013/054756, WIPO machine-generated English-language translation enclosed),
and in further view of:
ANSEL (Ansel, Howard C., et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems.” (1999), 7th ed. Lippincott Williams & Wilkins, pp. 48-53).
The instant claims are drawn to a method of reducing cytotoxicity of normal cells to anthracycline anticancer agents by first administering 5-aminolevulinic acid before administration of anthracycline doxorubicin. The instant dependent claims are further drawn to iron adjuvant therapies, and various dosages and dosing regimens of the above-mentioned 5-aminolevulinic acid/doxorubicin cocktail.
Determining the scope and contents of the prior art:
The prior art reference TSUKUBA teaches instant claims 1, 3-4, 11, 13, and 27, supra.
The SBI prior art reference teaches that the side effects of doxorubicin can be further reduced by administering an iron compound such as sodium ferrous citrate with the 5-aminolevulinic acid (para [0010], [0020], [0025], [0014]). Furthermore, the SBI para [0038] teaches most of the species of iron compounds per instant claims 2 and 12.
ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48).
Ascertaining the differences between the prior art and the claims at issue:
TSUKUBA does not teach the concentrations: dosages of instant claims 5-6; and the dosing regimens of instant claims 7-10. It also does not teach use of iron adjuvant therapy.
While SBI does not teach doxorubicin per se, it does teach use of 5-aminolevulinic acid and iron compound adjuvant therapy to reduce the side effects of cancer therapy (para [0010], [0020], [0025], [0014], and [0038]).
ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48). However, ANSEL does not teach the specific dosages and dosing regimens of instant claims 5-10.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in setting dosages and dosing regimens for active pharmaceutical ingredients. The artisan also knows how to use/add iron adjuvant therapy to cancer therapy to reduce side-effects towards cancer therapy.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would find prima facie obvious the use of iron adjuvant therapy, the dosages, and the dosing regimens of the claims 2, 5-10, and 12.
The artisan would be expected to add iron as an adjuvant therapy since it is known to help reduce side effects towards cancer therapy (SBI para [0037]).
The artisan would be motivated to add iron as an adjuvant therapy, such as using ferrous citrate, sodium iron citrate, or any of the plurality of iron compounds of SBI para [0038] in order to reduce the side-effects a patient has towards cancer therapy (SBI para [0037]-[0038]) since the use of iron adjuvant therapy is known in the prior art to help reduce the side-effects a patient would have towards cancer therapy (SBI, above). The use of iron adjuvant therapy per the teachings of SBI, above, would be a useful addition to a 5-aminolevulinic acid and doxorubicin therapy designed to reduce toxicity of the doxorubicin/anthracycline anticancer therapy as taught by TSUKUBA, above.
Moreover, the artisan would be expected to administer 5-aminolevulinic acid concurrently with doxorubicin (per TSUKUBA teachings, above) given that this itself constitutes a dosing regimen (a variable that is routinely optimized) that the artisan would be expected to vary to maximize therapeutic efficacy. The artisan would be motivated to administer 5-aminolevulinic acid concurrently with doxorubicin (per TSUKUBA teachings, above) given that this itself constitutes a dosing regimen and that the artisan would be expected to vary dosing regimens to maximize therapeutic efficacy. Thus, this teaches “administering 5-aminolevulinic acid concurrently with doxorubicin” per instant claim 27.
The artisan would be expected to vary the dosages and dosing regimens of the 5-aminolevulinic acid and doxorubicin taught in TSUKUBA in order to maximize treatment efficacy. The artisan would be motivated to vary the dosages and dosing regimens of 5-aminolevulinic acid and doxorubicin as variables that are routinely optimized in the pharmaceutical art) according to instant claims 5-10 to optimize the treatment efficacy and health of subjects receiving said treatment. This is especially true since neither the claims nor the Specification indicate how the concentrations (dosages and dosing regimens) within dependent (emphasis) claims 5-10 are critical. Moreover, the artisan would look to what is known in the pharmaceutical arts which shows that the physician routinely increases or decreases dosage and dosing regimens (concentrations/doses/dosing regimens) to meet the particular requirements of the patient (see ANSEL, page 48).
Moreover, patent law views differences in concentration (herein, the varying ranges of dosages and dosing regimens) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Thus, this teaches instant claims 1-13 and 27.
Conclusion
No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew D Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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