DETAILED ACTION
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 1-2, 6, 8, and 19 are pending. Claims 3-5, 7, 9-18, and 20-23 are cancelled.
Examiner previously required a restriction of the claimed inventions. The requirement filed on October 31, 2025 is now withdrawn and the prosecution will continue with a first non-final office action on the merits addressing the entire pending claim set.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/CN2021/077495, filed on February 23, 2021. This application also claims the benefits of foreign priority to CN202110156372.3, filed on February 04, 2021.
Specification - Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 8 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1.
Instant claim 8 is directed towards a medicine box or kit comprising the pharmaceutical composition according to claim 1 with no additional components specified. Therefore, the claim language of instant claim 8 suggests that the medicine box or kit can be identical to the pharmaceutical composition of instant claim 1. Therefore, claim 8 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a duplicate of the independent claim.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Examiner’s note on novelty and nonobviousness
The closest prior art is:
Zhang et al. (Zhang) (Zhang, X.-Y. et al. International Immunopharmacology 2005, 5, 1247-1257.)
Novelty:
Zhang discloses that in “mouse tumor xenograft models, intraperitoneal administrations of [proanthocyanidin] PA (10 mg/kg) daily or [doxorubicin] DOX (2 mg/kg) every other day for 9 days significantly inhibited the growth of sarcoma 180, whereas a combination of the two strongly inhibited tumor growth as compared with PA or DOX alone ( p < 0.01)” (abstract).
Note: according to the instant specification, DOX is also considered an agent which can cause cell senescence (pg. 36, lines 10-11).
Hence, Zhang teaches a pharmaceutical composition comprising:
a proanthocyanidin and
an agent capable of inducing a subject to produce a senescent cell (i.e., DOX)
which can be used to inhibit tumor growth in a subject (i.e., mice).
However, Zhang does not disclose a composition comprising:
specifically, procyanidin C1 (PCC1) and DOX or
specifically, procyanidin C1 and mitoxantrone (MIT)
which can be used to specifically promote prostate tumor regression, reduce prostate tumor size, or treat a prostate cancer.
Thus, the instant invention is considered novel.
Nonobviousness:
Both Zhang and the present invention disclose a composition comprising:
a naturally occurring polyphenolic bioflavonoid and
an agent capable of inducing a subject to produce a senescent cell (i.e., DOX).
However, Zhang does not teach nor suggest to:
replace proanthocyanidin with, specifically, PCC1 in the composition or
replace proanthocyanidin with, specifically, PCC1 and also replace DOX with MIT.
and to use the pharmaceutical composition specifically in promoting prostate tumor regression, reducing prostate tumor size, or treating prostate cancer.
Thus, the instant invention is considered nonobvious.
Claim Rejections - 35 USC § 112(a) - Enablement
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, 6, 8, and 19 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims a pharmaceutical composition containing (a) a procyanidin or pharmaceutically acceptable salt, hydrate or prodrug thereof, and (b) a reagent capable of inducing an object to generate senescent cells, and optionally, a pharmaceutically acceptable excipient. Disclosed is the use of the procyanidin or the pharmaceutically acceptable salt, hydrate or prodrug thereof and the pharmaceutical composition in the preparation of a drug or preparation for use in downregulating senescence-related secretory phenotype (SASP), reducing the expression or activity of an SASP factor, reducing the expression or activity of a marker factor of cell senescence, inducing non-proliferative cell apoptosis, reducing or eliminating non-proliferating cells, delaying senescence, prolonging the lifetime of an object, reducing the burden of senescence-related disease, preventing, relieving or treating diseases that benefit from the reduction or elimination of non-proliferating cells, reducing drug tolerance to cancer therapy, enhancing the efficacy of the reagent capable of inducing cell senescence, promoting tumor regression, reducing tumor volume, preventing or treating cancers, or prolonging cancer survival, especially for prostate cancer or tumors.
State of the prior art
See “Examiner’s note on novelty and nonobviousness” section above.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in oncology and medicinal chemistry and would be familiar with standard methods for evaluating therapeutic efficacy of compounds and/or compositions.
The presence or absence of working examples; the amount of direction or guidance present; and the quantity of experimentation necessary
The quantity of experimentation needed to make or use the invention must be considered to determine if undue experimentation is present. With regard to quantity of experimentation needed, (note Wolff et. al., "Burger's Medicinal Chemistry and Drug Discovery," 5th Ed. Part 1, pp. 975-977 (1995) provided with this action), which emphasizes the many experimental factors for consideration for a successful prodrug as well as the difficulty in extrapolating data from one species to another. See p.975-977. “Extensive development must be undertaken to find the correct chemical modification for a specific drug. Additionally, once a prodrug is formed, it is a new drug entity and therefore requires extensive and costly studies to determine safety and efficacy.” Banker, et. al., (1996), Modern Pharmaceutics, p.596, section “B. Prodrugs”, last paragraph. In view of all these factors undue experimentation would be required to practice the invention.
The scope of prodrugs is not adequately enabled or defined. Applicants provide no guidance as how the compounds are made more active in vivo nor do they provide any working examples of suitable prodrugs. The choice of a prodrug will vary from drug to drug. Therefore, more than minimal routine experimentation would be required to determine which ester, for instance, will be suitable for the instant invention. The application does not provide any guidance for one skilled in the art on how the prodrug is converted to active compounds, by what mechanisms and at what site the prodrug will be activated, what in vivo enzymes are likely involved in cleaving the protected group, etc.
Applicants provide no reasonable assurance that any and all known prodrugs will have the ability to regenerate in vivo to the instant compounds by one or more biological processes. It is not the norm that one can predict with any degree of accuracy a particular prodrug form of an active compound will be more soluble, more easily handled in formulations or more bioavailable without actual testing in vivo. Pursuant to In re Wands, 8 USPQ2d 1400, factors such as direction or guidance are not seen in the specification.
Many functional groups (e.g., hydroxy, amino groups) present in drugs are capable at least in theory to being derivatized but determining what is a prodrug and what is not requires knowledge of an intended effect (i.e. modification of an undesirable property in the parent drug- poor solubility, poor bioavailability, poor shelf-life) which is never identified by the specification.
Furthermore, the instant specification does not provide data that demonstrate the complete prevention of a prostate cancer.
Claim 8, which is dependent on claim 1, is also rejected for further requiring and/or reciting the non-enabling limitation, “prodrug,” of claim 1.
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, 6, 8, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 2, 6, and 19 recite “prodrug.” The term “prodrug” renders claims 1, 2, 6, and 19 indefinite as a prodrug does not have a defined structure known in the art. For example, one would not be apprised of the pharmacologically inactive form of the claimed compound from the simple recitation of “prodrug” as the compound itself has multiple sites to which a prodrug moiety could bind. Moreover, one could not ascertain as to which prodrug moieties are within the scope of the claim, resulting in millions of combinations of prodrug moieties associated with the claimed compound at different locations on its structure. One could not possibly envisage all the possibilities of a prodrug of any compound of the instant invention.
Claim 8, which is dependent on claim 1, is also rejected for further requiring and/or reciting the indefinite limitation, “prodrug,” of claim 1.
Claim 6 recites “comprising administering the subject in need thereof…”
Since Claim 6 is an independent claim, “the subject in need thereof” lacks proper antecedent basis. Accordingly, to address this 112(b) issue, Applicant should amend the claim to recite “comprising administering to a subject in need thereof…” instead.
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 8 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.
Instant claim 8 is directed towards a medicine box or kit comprising the pharmaceutical composition according to claim 1 with no additional components specified. Therefore, the claim language of instant claim 8 suggests that the medicine box or kit can be identical to the pharmaceutical composition of instant claim 1. Therefore, claim 8 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a duplicate of the independent claim.
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.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624