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 communication submitted May 17, 2023, wherein claims 3-7, 9-15, 17-25 were preliminarily amended, and claims 26-28 were added.
Claims 1-28 are pending in this application.
Priority
This application is a 371 of PCT/GB2021/052973 filed November 27, 2021 and claims foreign priority to GB2018068.3 filed November 17, 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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg. 27, last reference). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The disclosure is objected to because of the following informalities:
The page number and headers of each page are illegible.
On page 6 of the specification, the phrase “Steptoccoccus” should read “Streptococcus” (lines 9).
Appropriate correction is required.
Claim Objections
Claims 2-28 are objected to because of the following informalities:
Claims 2-28 are meant to dependent claims but start with the phrase “A pharmaceutical composition….”. If meant to be dependent claims, should start with “The pharmaceutical composition….” to avoid any confusion as to whether the claims are independent or dependent claims.
Claims 2, 4-5, 7-8, 9-12, 14-15, 25 attempt to recite dependency by referring to both the composition and the use, for example, “A pharmaceutical composition according to claim 1, for the use according to claim 1”. This adds confusion as to whether the composition or use is to be limited and should be in reference to the independent claim that is to be limited, i.e. “The pharmaceutical composition according to claim 1,”.
Claim 4 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 4 is generally unclear because it recites the pharmaceutical composition of claim 1, but attempts to include uses of any preceding claim (2-3), which are directed to compositional limitations. See MPEP § 608.01(n). Accordingly, claim 4 not been further treated on the merits.
Claims 5, 16, and 25 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim (i.e. claim 4 is the first multiple dependent claim). See MPEP § 608.01(n). Accordingly, the claims 5, 16, and 25 not been further treated on the merits.
In claim 25, recites “A pharmaceutical composition according to claim 1, any preceding claim for the use according to any preceding claim” is unclear.
In claim 28 the phrase “is one sected” should read “is one selected”.
In claim 28 the phrase “Steptococcus” should read “Streptococcus”.
Appropriate correction is required.
Claim Interpretation
With respect to instant claims 27-28, which are directed to a pharmaceutical composition and recites the phrase ““for use or method”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for use or method”, 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 1-28 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 enablement requirement. The specification, while being enabling for the treatment of conditions associated with a reduction in the number of Lactobacilli in the vagina of a subject relative to a healthy subject, does not reasonably provide enablement for the prevention of the same. The specification does not enable any person skilled in the art to which is pertains, or with which it is most clear connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)).
These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4)
relative skill in the art; (5) amount of direction provided by the inventor; (6) the level of
predictability in the art; (7) the existence of working examples; and (8) quantity of
experimentation needed to make or use the invention based on the content of the disclosure. All
of the factors have been considered with regard to the claim, with the most relevant factors
discussed below:
(1& 2) The breadth of the claims and nature of the invention: The claims are drawn to pharmaceutical compositions for the prevention or treatment of conditions associated with a reduction in the number of Lactobacilli in the vagina of a subject relative to a healthy subject comprising glycogen and lactic acid
(3) The state of the prior art: While there are publications that describe methods of treating conditions associated with a reduction in the number of Lactobacilli, there is no evidence in the prior art that the claimed composition would prevent all conditions encompassed from ever occurring as claimed. For example, Kira et al (Gynecology, 2015, cited on PTO-892, Machine English Translation provided) teaches that a composition comprising glycogen and lactic acid is a known medicament for the treatment of bacterial vaginosis (pg. 1, title, pg. 2, para. 2). Kira suggests that such a composition (tradename Lactagel® results in an increase in the number of lactobacilli and can cause a rapid decrease in the level of G. Vaginalis (pg. 4, para. 1). Kira suggests it may reduce the number of bacterial vaginosis relapses, and potentially prevent further recurrence (pg. 4, para. 1), but there is no evidence in the prior art that such a composition can do so without the undue burden of unpredictable experimentation. Thus, in short, the art recognizes administering therapeutic compositions containing glycogen can treat some conditions associated with lactobacilli, such as bacterial vaginosis, but not in the absolute prevention thereof.
(4) The level of skill in the art: The level of skill in the art would be high, mostly likely at
the Ph.D. /MD level.
(5 & 7) The amount of direction provided by the inventor and the existence of working
examples: Applicant has not provided examples that demonstrate that the composition claimed
is effective at preventing all conditions claimed. The instant specification has demonstrated that the compositions comprising glycogen leads to improvement in lactobacilli regrowth, vaginal pH, and lactic acid concentration (pg. 21, example 6) an can reduce the amount of Streptococcus infection in pregnant patients (pgs. 21-22, example 8, bridging para.). Applicant has not demonstrated that when the composition is administered to a subject, it would result in the absolute prevention of such condition or infection occurring.
(6) The level of predictability in the art: The prior art does not teach a method of preventing all conditions claimed by administering a therapeutic composition comprising glycogen. Although some methods may aid in the reduction of some diseases, there is nothing in the prior art that indicates that absolute prevention is possible.
(8) The quantity of experimentation necessary: Neither the instant specification nor the state of the art have demonstrated how therapeutic compositions, such as the composition claimed, can treat all disease or “prevent” all conditions from occurring. An undetermined number of experimental factors utilizing a composition and its method for preventing would have to be resolved by the practitioner and/or the patient for the following reasons: the factors are not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
Therefore, other than proposing an initial hypothesis, the entire burden of research
involved in utilizing the compositions claimed to prevent all conditions claimed would fall on the shoulders of the skilled artisan attempting to practice the claimed invention, presenting an undue burden of unpredictable experimentation.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a
reward for search, but compensation for its successful conclusion.” And “patent protection is
granted in return for an enabling disclosure of an invention, not for vague intimations of general
ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention without undue experimentation.
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 6, 11, 17-24, 27-28 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 claim 6: Claim 6 recites “wherein the glycogen is obtainable from an animal source”. The phrase renders the claim indefinite, because it is unclear whether the claim is reciting product by process claims, wherein the glycogen used is obtained from an animal source, is specifying the type of glycogen in the composition (i.e. animal glycogen), or is merely describing a general property of glycogen, in that it is obtainable from an animal source, which does not particularly limit the claim. Due to multiple interpretations, the claim is rendered indefinite.
Regarding claim 11: Claim 11 recites, “a pharmaceutical composition according to claim 1 for the use according to claim 1 which is a vaginal pessary.”. As written it is unclear whether the pharmaceutical composition itself is a pessary, or is meant to include within a pessary, which is a device. Due to the lack of clarity of the claim, it is rendered indefinite.
Regarding claims 17-24 and 27-28: Claims 17-24 and 27-28, which ultimately depend on claim 1 and recite the phrase “for use or method”, however, claim 1 merely recites “for use”, thus there is a lack of antecedent basis for the phrase “method” in the claims, thereby rendering them indefinite.
Regarding claim 18: Claim 18 recites the phrase “restoring the number of Lactobacilli in the vagina to a normal level”. However, the instant specification states in reference to a normal level, “the individualized nature of the vaginal microbiome makes the response to the pharmaceutical composition subject specific affording each patient their own 'Personalized microbiome therapy'.” (pg. 5, lines 17-19). Additionally, the instant specification states, “The number of Lactobacilli in a healthy subject is patient dependent, but a healthy premenopausal woman may have 107-108 CFU Lactobacilli mL-1 vaginal fluid.” (pg. 12, lines 11-12). The phrase “may have” is not an absolute standard and the instant specification states what constitutes normal may vary from patient to patient. Thus, the term “normal level” is a relative term which renders the claim indefinite. The term “normal level” 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. Thus, a person of ordinary skill in the art would be unable to determine what constitutes normal levels of lactobacilli in the vagina.
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.
Claims 17-24 and 27-28 are dependent claims of a composition, but recite limitations on intended use, 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 17-24 and 27-28, as best understood by the Examiner are interpreted to be dependent claims that ultimately depend on claim 1. Claims 17-24 and 27-28 however do not recite limitations of the composition of claim 1, but rather recite limitations on intended use. Thus the claims do not materially alter the structure of the composition of claim 1, and fail to further limit the 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.
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, 5-6, 9, 12-22, 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng (EP 2486922, IDS filed May 17, 2023).
Regarding claims 1, 5, 16, 20-21, 22, 24, 28: Zeng teaches the use of a low content of benzoic acid and/or sodium salt in combination with one or more organic acid preservative as active ingredients in the manufacture of a vaginal composition which has a weak inhibition effect on the normal vaginal lactobacilli while has strong inhibition effect on vaginal fungi and/or pathogenic vaginal lactobacilli (i.e. abstract). The composition of the invention useful for promoting normal vaginal lactobacilli and inhibiting vaginal fungi (pg. 4, para. 0023). The composition is applicable in treating vaginal microbial diseases, such as candidal vaginitis (pg. 4, para. 0026). Candidal vaginitis can result in vaginal inflammation (pg. 1, para. 0005). The composition is applicable to treatment of diseases with decreased lactobacilli and reduced vaginal acidity, such as bacterial vaginosis (pgs. 6-7, para. 0041). The composition can comprise between 0.1-15% (w/v) of one or more saccharides, which can be glycogen (pg. 7, para. 0048). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (See MPEP 2144.05 (I)). Additionally, differences in concentration or temperature will not support 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." (See MPEP 2144.05 (II)).
Regarding claim 2: Zeng does not teach the inclusion of lactic acid within the composition (i.e. no lactic acid).
Regarding claim 6: Wherein Zeng teaches glycogen, the ability of glycogen to be obtained from an animal source is a property that cannot be separated from the compound.
Regarding claims 9, 12-13, 26: Zeng teaches the composition can be formulated into a gel composition using a water-soluble gel matrix, most preferably Xantham gum, and water (i.e. excipient, pg. 5, para. 0031, pg. 10, para. 0066). Zeng teaches the water-soluble gel matrix homogenously contacts with vaginal mucosa and remains for a relatively long time (i.e. a mucoadhesive gel, pg. 6, para. 0035). Zeng teaches in a water-soluble gel composition the pH value is adjusted within the range from 3.5 to 6.5 (pg. 6, para. 0036). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (See MPEP 2144.05 (I)).
Regarding claims 14-15: Wherein the composition includes benzoic acid as an active ingredient, the composition comprising glycogen comprises an additional therapeutic agent. Additionally, Zeng teaches the composition can optionally comprise low content of antibacterial agents (pg. 7, para. 0043).
Regarding claims 17-19: Zeng teaches the composition promotes normal lactobacilli and maintains normal vaginal acidity and maintains vaginal acidity in a range from 3.8 to 4.1 (pg. 8, para. 0052). Zeng defines normal vaginal acidity to be preferably 3.7 to 4.1 (pg. 1, para. 0002).
Regarding claim 25: Zeng teaches the method includes intravaginal administration of the composition (pg. 8, paras. 0056-0057).
Regarding claims 27: Zeng teaches that killing normal vaginal lactobacilli and disrupting vaginal acidity result in decreasing natural resistance to infection, suggesting that the composition can be used to prevent/treat a recurrent vaginal infection (pg. 3, para. 0009).
Claims 3-4, 7-8, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng ‘922 (EP 2486922, IDS filed May 17, 2023) as applied to claims 1-2, 5-6, 9, 12-22, 24-28 above in view of Vanic (Hydrogels for Vaginal Drug Delivery, Functional Hydrogels in Drug Delivery, 2017, cited on PTO-892).
Regarding claims 3-4, 7-8, and 10: As discussed above, Zeng renders obvious the composition of claim 1. Zeng teaches the water-soluble gel matrix homogenously contacts with vaginal mucosa and remains for a relatively long time (i.e. a mucoadhesive gel, pg. 6, para. 0035).
Zeng does not teach wherein the composition comprises an aqueous hydrogel comprising hydroxypropyl methylcellulose.
However, Vanic teaches a majority of the commercially available vaginal gels and those in clinical investigations are mucoadhesive in nature (pg. 269, para. 2). They ensure a prolonged contact between the drug and vaginal mucosa, permitting the drug release over an extended period of time (pg. 269, para. 2). Vanic teaches the most commonly used cellulose derivatives include hydroxypropyl methylcellulose (pg. 269, para. 2). Vanic teaches that mucoadhesive polymers included in vaginal compositions can enhance residence time of the in situ formed hydrogels (pg. 269, para. 3). Vanic teaches that vaginal hydrogels are known in the art as delivery systems for active ingredients (pg. 269, para. 4).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Zeng, such that the composition is formulated as a hydrogel with hydroxypropylmethyl cellulose as taught by Vanic. A person of ordinary skill would have had the motivation to do so with a reasonable expectation of success given that inclusion of cellulose polymers, such as hydroxypropylmethyl cellulose, in hydrogel formulations for drug delivery are known techniques in the art of vaginal delivery of active ingredients.
Regarding claim 11: As discussed above, Zeng renders obvious the composition of claim 1. Zeng teaches the composition can be packaged in a vagina use device (pg. 7, para. 0046, pg. 8, para. 0051).
Zeng does not teach wherein the composition is a vaginal pessary.
However, Vanicc teaches pessary devices are known delivery methods for the active ingredients (pg. 280, para. 1).
Taken together it would have been prima facie obvious to modify the composition of Zeng, such that it is incorporated into a pessary, as taught by Griffiss, for vaginal administration of the active ingredients. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as pessaries are known devices in the art for vaginal administration of therapeutic compositions.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Zeng (EP 2486922, IDS filed May 17, 2023) as applied to claims 1-2, 5-6, 9, 12-22, and 24-28 above in view of Kira (Gynecology, 2015, cited on PTO-892). An English language machine translation of Kira has been provided by the Examiner.
Regarding claim 23: As discussed above, Zeng renders obvious the composition of claim 1. The composition is applicable to treatment of diseases with decreased lactobacilli and reduced vaginal acidity, such as bacterial vaginosis (pgs. 6-7, para. 0041).
Zeng does not teach wherein the subject to be treated is pregnant.
However, Kira teaches the treatment of bacterial vaginosis in pregnant women (English translation, pg. 4, para. 1).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to apply the composition for the treatment of bacterial vaginosis of Zeng to pregnant women as suggested by Kira. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as pregnant women can suffer from bacterial vaginosis and are a known subject population in need of treatment, and the composition of Zeng is a known therapeutic approach for this disorder.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.G./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693