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 June 7, 2023. This application was effectively filed June 7, 2023
Claims 1-6 are pending in this application.
Specification
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.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
In the instant application, the abstract uses the phrase “The present invention” as well as the legal phraseology “said”. Additionally the phrases “Polyethyleneimine” and “Chitosan” should not be capitalized”.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg. 1, paras. 0004, 0006). 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 following terms should not be capitalized: “Chitosan” (pg. 1, para. 0002, pg. 2, paras. 0007, 0016, pg. 3, para. 0019), “Polyethyleneimine” (pg. 2, para. 0007), “polymer” (pg. 4, para. 0028),
Appropriate correction is required.
Claim Objections
Claims 1-6 objected to because of the following informalities:
In claims 1-2, the term “Chitosan” should not be capitalized, it should read “chitosan”.
In claim 2 the phrase “administration to human” should read “administration to a human”.
In claim 3, the term “Blood-Brain Barrier” should not be capitalized, it should read “blood-brain barrier”. The acronym “BBB” can remain capitalized.
In claim 3 the phrase “the said conjugate” should read either “said conjugate” or “the conjugate”. See 112(b) issues below.
In claim 4, the terms “Asthma” and “Chronic Obstructive Pulmonary Disorder”should not be capitalized, it should read “asthma” and “chronic obstructive pulmonary disorder”. The acronym “COPD” can remain capitalized.
In claim 4, the phrase “asthma, chronic obstructive pulmonary disorder (COPD)” should read “asthma and chronic obstructive pulmonary disorder”. See 112(b) issues below regarding use of the phrase “like” preceding the phrase.
In claims 4-5, the term “Claimed” should not be capitalized, it should read “claimed”.
In claim 4 the phrase “The carrier drug conjugate system claimed in claim 1 is” should read “The carrier drug conjugate system of claim 1, wherein….”, or the like, To clearly establish the claim as a dependent claim. See 112(d) issues below regarding limiting a compound/composition claim.
In claim 5 the phrase “possess” should read “possesses”.
In claims 5-6 the phrase “The carrier drug conjugate system composition as claimed in claim 2” should read “The composition of the carrier drug conjugate of claim 2, wherein….” or the like, To clearly establish the claim as a dependent claim. See 112(d) issues below regarding limiting a compound/composition claim.
In claim 6, the term “Claim” should not be capitalized, it should read “claim”.
In claim 6, the phrase “is safe, non-toxic and biocompatible” should read “is safe, non-toxic, and biocompatible.”.
Appropriate correction is required.
Claim Interpretation
With respect to instant claims 1 and 3 which recite “coupled directly”, the phrase is interpreted to encompass covalent bonding between a functional group that is necessarily present in an active compound and a carrier substance, free of a linker or additional group.
With respect to instant claim 2, which is directed to a pharmaceutical composition and recites the phrase “suitable for oral/IV administration”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for oral/administration”, 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)).
With respect to instant claim 3, claim 3 does not properly depend from an independent claim. As written the claim does not recite a specific conjugate system, thus a carrier system comprising a carrier system coupled through an amide bond to an active compound anticipates the claim, so long as the carrier substance utilized is substantially resistant to permeation through the blood-brain barrier and stable under ambient conditions. The Examiner notes that the limitation recites “where the carrier substance is substantially resistant” and does not recite wherein the conjugate is substantially resistant. According to the instant specification, chitosan and polyethylene imine (PEI) are carrier substances that possess this property (pg. 2, para. 0016). Thus a conjugate to either anticipates this claim, given that these carriers possess this property.
Claims 4-6 are attempting to limit compound/composition claims by describing inherent properties “providing symptomatic relief”, “possess substantial inhibitory activity” and “safe, non-toxic, and biocompatible”. Wherein the compound/composition is taught by the prior art, these are inherent properties of the compound/composition that cannot be separated from the compound/composition, absent evidence the contrary. Thus, wherein the prior art teaches or renders obvious the claimed compound/composition, so too are the claims directed to these properties.
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 1-6 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 and 4-6: Claim 1 recites “A carrier drug conjugate system comprising montelukast coupled directly to a carrier substance, wherein the carrier substance is polyethyleneimine and/or Chitosan. Claim 2 recites inter alia, “….wherein the system Specifically the phrase “polyethyleneimine and/or chitosan” in each claim renders the claims indefinite, because it is unclear whether claim is including (i.e. a conjugate to both polyethyleneimine and chitosan simultaneously) or is meant to list them in the alternative (i.e. either polyethyleneimine or chitosan). The instant specification only describes conjugation to polyethyleneimine (pgs. 5-6, para. 0041). Additionally, the claim is rendered 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: the connectivity between montelukast and polyethyleneimine and/or chitosan. The drawings of the instant specification that the conjugate between montelukast and PEI is coupled through the montelukast amide (drawings figure 2), is the chitosan to be conjugated similarly? Is the bi-conjugate (i.e. PEI and chitosan) connected to each-other, or connected to montelukast in separate locations?. Claims 4 and 5-6 which depend from claims 1 and 2 respectively, are similarly rejected.
Regarding claims 2 and 5-6: Claim 2 recites “A composition of the carrier drug conjugate suitable for oral/IV administration to human wherein the system is made of 1 g of polyethyleneimine (PEI) and/or Chitosan, 500 mg montelukast and at least one inert diluent such as sterile/water for injection.” The phrase “wherein the system is made of 1 g of polyethyleneimine (PEI) and/or Chitosan, 500 mg montelukast and at least one inert diluent such as sterile/water for injection.” renders the claim indefinite because it is unclear whether the claim is describing a composition, that is a mixture of 500 mg montelukast, 1g of polyethyleneimine and/or chitosan and a diluent, or is a composition comprising the conjugate and a diluent, and reciting product-by process limitations on forming the conjugate (i.e. reacting 1 g of PEI with 500 mg montelukast to form the conjugate). Claims 5-6 which depend from claim 2 are similarly rejected. According to the instant specification the conjugate is synthesized from reacting 500 mg of montelukast and 1g of PEI (pgs. 5-6, para. 0041). Based upon this description, for examination purposes the claims will be interpreted to be directed towards a composition comprising the conjugate and a diluent and thus the limitations with respect to the amount of PEI or chitosan and montelukast are non-limiting.
Regarding claim 2, the phrase "such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 2, which recites the limitations "the carrier drug conjugate”. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 2, which recites inter alia, “suitable for oral/IV administration” but also the phrase “such as sterile/water for injection”. It is unclear whether this diluents are also acceptable for oral formulation, given that the beginning of the claim also recites oral administration as a formulation. See claim interpretation above with respect to intended use claims.
Regarding claim 3 which recite the limitation "The carrier drug conjugate system”. There is insufficient antecedent basis for this limitations in the claim.
Regarding claim 3 which recites the limitations "the active", “the carrier system”. There is insufficient antecedent basis for these limitations in the claim. Additionally, based on the claim, it is unclear what the phrase “the active” would be in reference to. For examination purposes “the active” will be interpreted to be montelukast as described in the instant specification (pg. 1, para. 0002). Also see 112(d) issues below.
Regarding claim 3 which recites inter alia, “wherein the said conjugate comprising of an active coupled directly to a carrier substance”. It is unclear what is to be limited by the recitation of this phrase as the claim already recites “….is coupled through an amide bond between the active and the carrier system….”. The lack of clarity renders the claim indefinite.
Regarding claim 4: Claim 4 recites inter alia, “….is providing symptomatic relief in conditions….”. It is unclear whether this claim is merely describing a property following administration as in a method claim, or is describing a property of the conjugate system. Thus, claim 4 is rendered indefinite.
Regarding claim 5, the phrase "like” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 5, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Additionally the phrase “possess substantial inhibitory activity against the inflammatory modulators” renders the claim indefinite because it is unclear whether the claim is meant to limit to specific inflammatory modulators, or the inflammatory modulators as a collective class of drug targets.
Regarding claim 6: Claim 6 recites inter alia, “….is safe, non-toxic and biocompatible….”. It is unclear whether the phrase is merely describing a further property of the conjugate, or is meant to impart some form of structural modification that results in the conjugate being safe, non-toxic, and biocompatible.
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 4-6 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.
Regarding claim 4 which is directed to a conjugate system, depends from claim 1, and recites inter alia, “….is providing symptomatic relief in conditions like asthma, chronic obstructive pulmonary disorder “COPD”. The claim is describing properties of the conjugate system upon administration to the subject. This description of properties does not impart any additional structural limitations on the conjugate of claim 1 and thus fails to further limit the claim.
Regarding claim 5 which is directed to a composition, depends from claim 2, and recites inter alia, “possess substantial inhibitory activity against the inflammatory modulators….”. The claim is describing properties of the composition. This description of properties does not impart any additional structural limitations on the composition of claim 2 and thus fails to further limit the claim.
Regarding claim 6 which is directed to a composition, depends from claim 2, and recites inter alia, “….is safe, non-toxic and biocompatible….”. The claim is describing properties of the composition. This description of properties does not impart any additional structural limitations on the composition of claim 2 and thus fails 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 § 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.
Claim 3 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kafedjiiski (Pharmaceutical Research, 2005, cited on PTO-892).
Regarding claim 3: Kafedjiiski teaches a chitosan-GSH (carrier substance-active) conjugate through direct coupling via an amide bond (pg. 1481, fig. 1). Kafedjiiski teaches that the conjugates were stable (abstract, pg. 1483, col. 2, para. 3). Although Kafedjiiski does not teach wherein the carrier substance is substantially resistant to permeation through the blood-brain barrier, according to the instant specification, chitosan is one such carrier substance (pg. 2, para. 0016). Thus, wherein the conjugate comprises chitosan, the conjugate necessarily comprises a carrier substance that is substantially resistant to permeation through the blood-brain barrier.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Sato (US 2016/0158369, cited on PTO-892) as evidenced by Tahan (Clinical and Experimental Allergy, 2008, cited on PTO-892).
Regarding claims 2 and 5-6: Sato teaches pharmaceutical compositions for respiratory administration containing a polysaccharide covalently bonded to an active compound for the purpose of treating chronic obstructive pulmonary disorder (COPD) (abstract, pg. 1, para. 0005). Sato teaches the preparation of montelukast covalently conjugated to chondroitin sulfate with an amino containing linker (pg. 23, paras. 0261-0264). Sato teaches 560 mg of chondroitin sulfate are reacted with 140 mg of the montelukast derivative (pg. 23, para. 0264). Isolation of said compound is interpreted as the compound being stable under ambient conditions. Sato teaches the compounds are to be administered intratracheally (i.e. orally) in aqueous solution (pg. 31, para. 0363, pg. 32, para. 0368)
Sato does not explicitly teach wherein the montelukast is covalently conjugated to chitosan.
However, Sato teaches that the compounds of the invention can be conjugated with chitosan as an alternative polysaccharide (abstract, pg. 2, para. 0024). Sato demonstrates the conjugation of other active components with chitosan (pg. 24, paras. 0271, pgs. 24-25, para. 0272). Wherein both chondroitin sulfate and chitosan are both possible polysaccharides to be conjugated to montelukast for respiratory administration, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the montelukast-chondroitin sulfate conjugate by substituting chondroitin sulfate with chitosan as suggested by Sato. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as chitosan is taught as an acceptable alternative polysaccharide to be conjugated to the active component (montelukast) for the purpose of respiratory administration for the treatment of COPD.
Although Sato does not teach wherein the conjugate system possess substantial inhibitory activity against inflammatory modulators, is safe, non-toxic, and biocompatible, given that the composition is rendered obvious, these properties naturally flow from the suggestion of the prior art, absent evidence to the contrary. As discussed above, Sato teaches the composition is to be administered to subjects (i.e. biocompatible). Additionally, Tahan discloses that Montelukast inhibits TNF-alpha stimulated IL-8 expression (abstract).
Regarding claims 1, 3, and 4: As discussed above, Sato renders obvious a conjugate between montelukast and chitosan by way of linker for the purpose of treating COPD (i.e. providing symptomatic relief.
Sato does not explicitly teach wherein montelukast is directly coupled to the carrier through an amide bond.
However, Sato teaches that alternatively to use of a linker, the active compound (i.e. montelukast) can be directly conjugated to the polysaccharide utilizing functional groups of the polysaccharide (carboxy, amino, or hydroxyl) and active compound (Carboxy or amino) (pg. 5, para. 0076, pg. 10, para. 0149). Sato in explicit examples teaches manipulation of the carboxyl group of montelukast, as described in the chondroitin sulfate conjugate above (pg. 23, paras. 0261-0264). Sato in explicit examples teaches manipulation of the amino group of chitosan (pgs. 24-25, para. 0272). Given the suggestion of direct conjugation, a person of ordinary skill would recognize the ability to couple the carboxylic acid of montelukast and the amino of chitosan through an amide bond.
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to further modify the conjugate of Sato such that montelukast and chitosan are directly conjugated by reacting the carboxy of montelukast and amino of chitosan, forming an amide bond. A person of ordinary skill in the art would have had the motivation do so with a reasonable expectation of success given that Sato suggests either direct coupling or use of a linker are viable alternatives in conjugating montelukast to polysaccharides such as chitosan and demonstrates the manipulation of functionalities that would result in an amide bond. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (See MPEP 2123 (II)).
Although Sato does not teach wherein the carrier substance is substantially resistant to permeation through the blood-brain barrier, according to the instant specification, chitosan is one such carrier substance (pg. 2, para. 0016). Thus, wherein the conjugate comprises chitosan, the conjugate necessarily comprises a carrier substance that is substantially resistant to permeation through the blood-brain barrier.
Conclusion
No claims are allowed in this action.
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/S.L.G./Examiner, Art Unit 1693
/ERIC OLSON/Primary Examiner, Art Unit 1693