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 .
Election/Restrictions
Applicant’s election of Compound 30 as the elected species in the reply filed on 07/27/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The elected compound 30 appears to be free of art. Accordingly, the search is extended to next species (examiner’s choice) for examination.
Claim Objections
Claims 1, 2 and 4 are objected to because of the following informalities:
-Each claim must begin with a capital letter and end with a period, and periods may not be used elsewhere in the claims. This is a formal requirement under MPEP §608.01(m) and is part of the Office’s preferred format for claims.
In line 13 of page 3 and line 12 of page 4 of claim 1, line 6 of claim 2, and line 5 of page 5 of claim 4, additional periods are present.
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Appropriate correction is requested.
-It is also noted that bracketed “[ ]” expression is typically used to indicate deletion of claim text. For the clarity, it is suggested that the “[ ]“ notation in claim 1 be removed and, if necessary, replaced with comma.
Appropriate correction is requested.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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.
Claim 11 is rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating the specific disease condition involving H-PGDS, for example “asthma, chronic obstructive pulmonary disease, allergic rhinitis, et…” recited in claim 12, does not reasonably provide enablement for the prevention or treatment of a disease state or condition mediated by H-PGDS. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
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”. These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the prior art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor, 7) the existence of working examples, and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
1) The breadth of the claims: Dictionary.com defines “prevent” as “keep something from happening or arising”. Therefore, given BRI, the instant claimed invention is construed as total eradication or treatment of a disease state or condition mediated by H-PGDS are known or that to be discovered in the future.
2) The nature of the invention: The nature of the invention is therefore drawn to the pharmaceutical art. These claims cover diseases that are known to exist and those that may be discovered in the future, for which there is no enablement provided.
3) The state of the prior art and 4) the level of predictability in the art: The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face. While a full discussion of each disease which is encompasses by Applicant's claim language will not be given, the following examples teach that the state of the prior art with respect to the claimed diseases has not advanced to the point of being predictive of the prevention or treatment of the breadth of diseases instantly claimed.
H-PGDS is one of the enzymes involved in prostaglandin synthesis, specifically involving the conversion of prostaglandin H2 to prostaglandin D2. As described by Christ et al. (Reference included with PTO-1449) there are several different prostanoids with different biological activities involved in inflammatory processes. (p. 5536 left column first paragraph) While PGD2 is present in various tissues throughout the body, its synthesis form PGH2 is carried out by two distinct enzymes, lipocalin-PGDS and hematopoietic PGDS. (p. p. 5536 right column second and third paragraphs) Since these two enzymes are expressed in different tissues, (see e.g. p. 5537 left column first paragraph) the mere fact that PGD2 is involved in a particular biological process is not a guarantee that inhibiting H-PGDS will affect said condition. In particular, as Christ describes L-PGDS activity as occurring in the central nervous system, testis, and heart, the effect of inhibiting H-PGDS on conditions of these tissues, for example amyotrophic lateral sclerosis or cerebral ischemia as recited in claim 29, is not predictable. Specific inhibitors of H-PGDS, for example the compound HQL-79, are known in the art and have been tested as therapeutic agents for specific diseases. For example, Nagalla (Reference included with PTO-1449) discloses that HQL-79 can prevent ant reverse cardiovascular remodeling induced by pressure overload. (pp. 41-48, aim 3) Rittchen et al. (Reference included with PTO-1449) generally discloses beneficial effects of H-PGDS inhibition in a wide range of inflammatory and allergic conditions. (pp. 9-11 section 4) Mohri et al. (Reference included with PTO-1449) discloses that HQL-79 can ameliorate muscular necrosis and muscular dystrophy(abstract). However, given the wide distribution and many roles of PGD2 and the existence of the alternate L-PGDS enzyme that also produces this compound, it is not possible to extrapolate from any of these particular results to a general treatment or prevention of a wide variety of different diseases as recited in claims 11.
Furthermore, looking into some of the conditions recited in claim 11 as being involved with h-PGDS, as described by Marks et al. and Mutius et al. (References included with PTO-892) preventative strategies for asthma involve dietary and environmental interventions rather than drug therapy. According to Zhang et al., (Reference included with PTO-892) preventative strategies for muscular dystrophy focus on gene editing rather than administering inhibitors of any particular enzyme. According to Alpizar-Rodriguez (Reference included with PTO-892) clinical trials have been undertaken to study possible preventative interventions for patients in the early stages of rheumatoid arthritis. (p. 1385) However none of these trials has successfully demonstrated prevention of disease onset. Caldwell (Reference included with PTO-892) discloses that some drug therapies for the prevention of myocardial infarction have been studied. (pp. 209 right column last paragraph – p. 211 right column fourth paragraph) However, aside from aspirin, the drug therapies discussed involve control of other predisposing factors such as hyperlipidemia, hypertension, or diabetes. Therefore, looking to the totality of the evidence, one skilled in the art would not consider prevention of all of these diseases with a drug targeting a single inflammatory mediator to be a realistic possibility.
5) The level of one of ordinary skill: The artisans using applicant's method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience. The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
6) The amount of direction provided by the inventor and 7) working examples: The specification provides no direction or guidance for preventing or treating every disease conditions encompassed by the claimed invention. No reasonably specific guidance is provided concerning useful therapeutic protocols for said cancers, other than inhibition of CDK7. The latter is corroborated by tables in the specification on pages 188-193. The disclosure does not provide how the in vitro data correlates to the prevention or treatment of the assorted disorders of the instant claims. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved." See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In order to practice the full scope of the claimed invention for all possible diseases, one skilled in the art would have to first determine which diseases are actually treatable.
As discussed previously, it is unclear form the prior art what the full scope of diseases treatable by inhibiting h-PGDS is, and one skilled in the art would not have any assurance that the disclosed compounds can in fact be used to treat any disease whatsoever that is associated with this enzyme. Actually enabling the full scope of the claimed invention would require an extensive program of novel and unpredictable research into numerous different diseases, constituting an undue burden of unpredictable research in order to practice the claimed invention.
8) The quality of experimentation necessary: A person having ordinary skill in the art at the time the invention was made would be faced with an undue amount of experimentation to use the pharmaceutic al compositions for the full scope of the claimed intended uses.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states 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 and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds encompassed in the instant claims, with no assurance of success.
Furthermore, there is no evidence of record, which would enable the skilled artisan in the identification of the people who have the potential of becoming afflicted with the numerous diseases/disorders or conditions claimed herein. That a single compound can be used to prevent or treat all diseases/disorders and conditions embraced by the claim is an incredible finding for which Applicant has not provided supporting evidence. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for treating any or all of the diseases/disorders or conditions by administering the instant claimed compound.
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 1-8 and 10-13 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 claims 1 and 6 recite parenthetical expression “when there are multiple R4’s, each R4 independently represents” and “when there are multiple R5’s, each R5 independently represents” respectively. Parenthetical expressions are not generally permissible which do not contribute to clearness or exactness in stating Applicant’s invention (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). Here, the recited parenthetical language raises uncertainty as to the scope of the claims because the subject matter contained within the parentheses is not identical in scope to the surrounding claim language. Accordingly, the parenthetical recitations create ambiguity as to whether the language is intended as a mandatory limitation, an explanatory statement, or an optional construction rule. As such, claims 1 and 6 are indefinite.
For the examination purpose, these recitations are optional elements.
Claims 2-5, 7-8, and 10-13 are rejected for the same reason. These claims depend directly or indirectly from rejected independent claim 1, or otherwise recite the same indefinite limitation set forth in claim 1. The deficiencies noted above are therefore not cured by the dependent claims. In particular, claims 11 and 12, although recited in method format, still include the same limitation from claim 1; thus, the indefiniteness is not overcome.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over (allowed) claims 1-5, 7-10, 12-25 and 27-30 copending Application No. 18/002232. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘232 makes obvious the present claims. Specifically, claim 1 of ‘232 claims a compound having a structure that overlaps with the structure (I) recited in present claim 1. Claim 2 of ‘232 further defines variables X represented by General Formula (II) overlaps with Z group represented by the Formula II of the instant claim 2, when p is zero. Dependent claims 3-5, 7-10, 12-25 of ‘232 add further limitations which make obvious the further limitations recited in present dependent claims 3-7, 10 and 13. Claims 28 and 30 of ‘232 claim pharmaceutical compositions and methods which are equivalent to those recited in present claims 11-12.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
-WO 2019/084300 A1 and WO 2010/104024 A1 are the closest prior art because they describe compounds with similar structures to the compounds represented by formula (I) in the present invention (WO’300, particularly, the compounds in the bottom section of page 123 and the bottom section of page 124; WO’024, particularly, the compounds of examples 8-10). However, neither reference discloses or suggests the presently claimed compounds, nor do they disclose or suggest the use of the compounds as H-PGDS inhibitors.
Further, WO 2017/128917 discloses parazole condensed-ring derivatives represented by the Formula I
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for use in treating cancer, inflammation and immune disease. However, WO’917 does not disclose or suggest the instant claimed invention, nor does it provide any teaching or motivation that would have lead one of ordinary skill in the art to arrive at the claimed compounds or their use as H-PGDS inhibitors.
-Claim 9 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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/BRIAN-YONG S KWON/ Supervisory Patent Examiner, Art Unit 1613
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