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.
This office action is a response to applicant’s response to election submitted January 12, 2026. The claims filed June 22, 2023 are examined herein wherein claims 18 and 20 were preliminarily amended, claim 17 was cancelled, and claim 21 was added.
Claims 1-16 and 18-21 are pending in this application.
Priority
This application is a 371 of PCT/CN2021/140028 December 21, 2021 and claims foreign priority to CN2020115322304.4 filed December 22, 2020 and CN202011532338.3 filed December 22, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. The Examiner notes that no English language translation was provided.
Election
Applicant’s election with traverse of Group I claims 1-16 and “an FA-polysialic acid-conjugated molecule” in the reply filed January 12, 2026 is acknowledged.
Claims 3, 5-8, 13, 15 and 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant stated that claim 13 was encompassed by the elected species, however claim 13 is directed towards molecules wherein the calcification-inducing unit is a repeating sequence of polyglutamic acid or casein phosphopeptide, not an FA-polysialic acid conjugate as is elected. Thus, claim 13 is withdrawn as well. Election was made with traverse in the reply filed on January 12, 2026. Because applicant did not distinctly and specifically point out the supposed errors in the election requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-2, 4, 9-12, 14 and 16 are encompassed by the elected species and examined herein.
Information Disclosure Statement
The information disclosure statement filed June 22, 2023 fails to comply with 37 CFR 1.98(a)(1), which requires the following: (1) a list of all patents, publications, applications, or other information submitted for consideration by the Office; (2) U.S. patents and U.S. patent application publications listed in a section separately from citations of other documents; (3) the application number of the application in which the information disclosure statement is being submitted on each page of the list; (4) a column that provides a blank space next to each document to be considered, for the examiner’s initials; and (5) a heading that clearly indicates that the list is an information disclosure statement. The information disclosure statement filed June 22, 2023 appears to be missing US document numbers, publication date, and name of patentee for four references. It is unclear if this implies no additional references were to be added, or is a typo. The information disclosure statement has been placed in the application file, but the information referred to therein has not been considered.
Specification
The disclosure is objected to because of the following informalities:
The Scheme on page 15 is blurry, particularly the NH2 groups, which presents an issue of clarity (middle of page).
The structure on page 18 is blurry, particularly the OSO3- groups, which presents an issue of clarity (middle of page).
Appropriate correction is required.
Claim Objections
Claim 14 is objected to because of the following informalities:
In claim 14 the “FA” acronym should be defined prior to its use. Although it is defined in instant claim 4, claim 14 does not depend from claim 4 and thus should be defined in this claim as well. Appropriate correction is required.
Claim Interpretation
With respect to instant claim 16, which is directed to a compound and recites the phrase ““for inducing spontaneous calcification of tumor cells of claim 1, wherein the tumor cells are…”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for inducing spontaneous calcification”, will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)).
Claim Rejections - 35 USC § 112 (a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4, 9-12, 14 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require “a molecule for inducing the spontaneous calcification of the tumor cells comprises at least two basic units, one of the at least two basic units is a targeting functional unit, the targeting functional unit targets a molecular region of the tumor cells or a tissue or a microenvironment, and the other basic unit is a calcification-inducing functional unit; or wherein the molecule for inducing the spontaneous calcification of the tumor cells comprises at least one basic unit, and the at least one basic unit is both the targeting functional unit and the calcification-inducing functional unit.”. The claims do not require that the molecule possess any particular conserved structure, or other distinguishing feature. Thus, the claims are drawn to a genus of compounds that is defined by novelty.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). Thus, an applicant complies with the written-description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
This case was filed before Applicants had a clear idea of the structures of their desired compounds, how to make their compounds and how to use them.
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is.” See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
Therefore, the full breadth of the claim fails to meet the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4, 9-12, 14, and 16 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.
Regarding claims 1-2, 4, 9-12, 14 and 16: The elected species recites “an FA-polysialic acid-conjugated molecule” as is encompassed by claim 1. However, the phrase “an FA-polysialic acid-conjugated molecule” renders the claim indefinite because it is unclear whether the phrase is describing a molecule that is conjugated to FA-polysialic acid, or whether the molecule encompassed is merely the conjugation between FA and polysialic acid, as is shown on page 15 of the instant specification (middle of page). Moreover, the phrase renders claim 1 indefinite as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Structurally connectivity between the FA, polysialic acid and/or molecule that are encompassed by the claim. Claims 2, 4, 9-12, 14 and 16, which depend from claim 1 are similarly rejected. For Examination purposes, the phrase will be interpreted such that it encompasses the conjugation between FA and polysialic acid as well as conjugates between FA, polysialic acid, and a molecule, given the broadest reasonable interpretation of the phrase “an FA-polysialic acid-conjugated molecule”.
Claim Rejections - 35 USC § 112 (d)
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.
Claim 16 is 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.
Claim 16 which ultimately depend from claim 1 drawn to a molecule, attempt to limit claim 1 via intended use/purpose. However, wherein the base claim 1 is drawn to a specific molecule, limiting by intended use does not limit the structure of the compound of claim 1, absent evidence to the contrary. In short, dependent claims fail to limit 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 § 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 1-2, 4, 9-12, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Yoo (J. Controlled Release, 2004, cited on PTO-892) in view of Zhang (Asian Journal of Pharmaceutical Science, 2014, cited on PTO-892) and Greco (Polym. Chem., 2013, cited on PTO-892) as evidenced by Tang (Angew. Chem. Int. Ed., 2021, cited on PTO-892) and Zhang (Nat. Biotechnol., 2025, cited on PTO-892). The supporting information of Tang has been provided by the Examiner.
Regarding claims 1-2, 4, 9-12, 14 and 16: Yoo teaches a folate-receptor targeted anticancer therapy utilizing a doxorubicin-polyethylene glycol-folate (DOX-PEG-FOL) conjugate (abstract). Yoo teaches the following synthesis of such a conjugate
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, wherein folate is conjugated to PEG and then conjugated to doxorubicin (pg. 250, figure 2). Yoo teaches folate receptors are overexpressed in several human tumors including ovarian and breast cancers (pg. 248, col. 1 para. 1). Yoo teaches such conjugates exposing folate on the surface can result in selective targeting behaviors against folate-positive cancer cells (pg. 248, cols. 1-2, bridging para.). Thus, the conjugate of Yoo, that possess a folate molecule (i.e. targeting functional unit), targets a molecular region of tumor cells, such as ovarian or breast.
Yoo does not teach wherein the peg group in the folate-peg-dox conjugate is replaced with polysialic acid.
However, Zhang (Asian Journal of Pharmaceutical Science, 2014) teaches polysialic acid (PSA) is an improvement to PEG in drug delivery systems (pg. 77, col. 1, last para., col. 2, para. 2). Zhang (Asian Journal of Pharmaceutical Science, 2014) teaches PSA on the surface of drugs/carriers will provide a water cloud barrier owing to its high hydrophilicity and chain flexibility (pg. 77, col. 2, para. 2). The cloud protects modified drugs/carriers from interacting with plasma proteins or macrophages, prolonging circulation half-life (pg. 77, col. 2, para. 2). Zhang (Asian Journal of Pharmaceutical Science, 2014) teaches PSA has potential to be conjugated to low molecular weight anti-cancer drugs, such as in a PSA-epirubic conjugate (pg. 77, col. 2, para. 5). Conjugation to epirubic resulted in improved anti-cancer activity as well as a significantly longer retention than free epirubic alone (pg. 77, col. 2, para. 5). Additionally, Greco, which is cited by Zhang (Asian Journal of Pharmaceutical Science, 2014), teaches the preparation of a PSA-Epi polymer-drug conjugate as a therapeutic for breast cancer (abstract). Greco suggests that the polymer-drug conjugates can be combined with a targeting moiety for active targeting (pg. 1600, col. 1, para. 2).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the teachings of Yoo by substituting PEG with pSA as suggested by Zhang (Asian Journal of Pharmaceutical Science, 2014) and Greco. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art establishes PSA conjugates are known in the art, PSA is known as a general improvement over PEG in drug delivery systems, and the art contemplates conjugates comprising PSA, a small molecule, and a targeting agent (i.e. folate). A person of ordinary skill in the art would recognize the added benefit of utilizing PSA as it can protect modified drugs/carriers from interacting with plasma proteins or macrophages and prolong circulation half-life. Wherein PEG and PSA are known as the art as conjugatable drug delivery systems for small molecules, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06
Although the prior art relied upon does not explicitly state the ability of the PSA unit to induce calcification in tumor cells, according to the instant specification the molecule can be a folate-polysialic acid crosslinked molecule, wherein folate acid is responsible for binding highly expressed receptor proteins on the surface of cancer cells to prevent off-target effects, and the functional end of the calcification portion is polysialic acid, which comprises a large number of free carboxyl groups and is responsible for enriching calcium and phosphate ions in the microenvironment to induce calcification (pg. 5, para. 0026). Tang discloses that doxorubicin as well as a Folate-polysia conjugates are capable of inducing calcification in tumor cells (Supporting information, pg. 18, Figure S10d). Zhang (Nat. Biotechnol., 2025) discloses that PSA in antibody conjugates facilitate calcium ion enrichment, inducing surface calcification and bacterial death (abstract, pg. 2, col. 1, para. 2). Thus, wherein the molecule rendered obvious over the prior art comprises folic acid conjugated to polysialic acid with free carboxyl groups, as well as doxorubicin, the compound necessarily is capable of targeting and inducing spontaneous calcification in tumor cells, absent evidence to the contrary. Additionally through the synthesis of a DOX-PSA-FOL conjugate, a person of ordinary skill following the synthetic protocol would necessarily arrive at producing a PSA-FOL conjugate as an intermediate.
Conclusion
No claims are allowed in this action.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Zhang (Drug Delivery, 2018) teaches mixed polysialic acid micelles with folate for the treatment of Rheumatoid arthritis (abstract).
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693