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 .
DETAILED ACTION
RESPONSE TO ELECTION/RESTRICTION
Applicant’s election of group II, drawn to compounds of the formula IIb and simple compositions thereof and elected species of compound 23:
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in the reply filed on 4/29/2026 is acknowledged. There is still ambiguity regarding the language of claim 1 encompassing the elected species with respect to variable L which will be addressed in the office action. 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 § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 2-5, 9-25, and 27-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
An action on the merits of claims 1, 6-8, and 26 is contained herein. Applicant’s elected species was found free of the art and the search extended to cover a proper Markush grouping embracing the core of Applicant’s elected species along with limiting W2 to the working embodiment cyclen.
Priority
This application is a Continuation of PCT Patent Application No. PCT/IL2022/050059 having International filing date of January 14, 2022, which claims the benefit of priority under 35 USC §119(e) of U.S. Provisional Patent Application No. 63/137,300 filed on January 14, 2021. Benefit for the provisional application is not accorded since subject matter disclosed within the instant application is not supported (e.g. scope of variable W2 possessing moiety P). The claims in a U.S. application are entitled to the benefit of a foreign priority date or the filing date of a provisional application if the corresponding foreign application or provisional application supports the claims in the manner required by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. In re Ziegler, 992 F.2d 1197, 1200, 26 USPQ2d 1600, 1603 (Fed. Cir. 1993); Kawaiv.Metlesics, 480 F.2d 880, 178 USPQ 158 (CCPA 1973); In re Gosteli, 872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989).
Information Disclosure Statement
The examiner has considered the references cited in the information disclosure statement filed of record.
Specification
Applicant is reminded of the proper content of an Abstract of the Disclosure, see MPEP 608.01(b).
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., "The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics." Exemplification of a species could be illustrative of members of the class. For processes, the type reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
It is recommended that the structure of Formula IIb be inserted into the abstract to accurately illustrate the claimed invention.
Claim Objections
Claims 1, 6-8, and 26 are objected to because the claims should be amended to represent only the elected invention of group II, drawn to compounds of the formula IIb and simple compositions thereof. Thus the claims are objected to. Correction is required.
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, 6-8, and 26 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 pre-AIA the applicant regards as the invention.
In claim 1 for variable L, the language:
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is unclear with respect to the amended language. The above states that the variable could be an “aliphatic linking moiety” or an “aromatic linking moiety which includes an aryl in its chain”. The latter suggesting that the two options are independent of each other wherein the language “includes an aryl in its chain” pertains to the aromatic group only. However the elected species appear to embrace the limitation wherein the variable is an aliphatic linking moiety which also includes an aryl. Thus, does the inclusion of the aryl moiety apply to both options or just the aromatic moiety? Thus the scope is unclear and claims dependent on the generic claim is indefinite. Correction is required.
For variable W2, the limitation “with the W attached thereof” is unclear since there is no variable “W” mentioned prior in the definition recited therein.
See In re Zletz, 13 USPQ2d 1320, 1322, “An essential purpose of patent examination is to fashion claims that are precise, clear, correct and unambiguous.”
Claim Rejections – Improper Markush Grouping Rejection
Claims 1, 6-8, and 26 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
In re Harnish, 206 USPQ 300, 305, says, “ …we think it should be clear from our actions in Weber and Haas II that we there recognized the possibility of such a thing as an "improper Markush grouping." The court went on to reverse the rejection, (which had been made by the Board under Rule 196(b)) but not on the lack of a specific statutory basis but rather, “Clearly, they are all coumarin compounds which the board admitted to be "a single structural similarity." We hold, therefore, that the claimed compounds all belong to a subgenus, as defined by appellant, which is not repugnant to scientific classification (see claim 1 below for pictorial example):
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.
Under these circumstances we consider the claimed compounds to be part of a single invention so that there is unity of invention…” Thus, the rejection was overturned because of the specific facts in the case. The Markush group was held proper in that case, as was the case also in Ex parte Price 150 USPQ 467, Ex parte Beck and Taylor, 119 USPQ 100, and Ex parte Della Bella and Chiarino 7 USPQ2d 1669. Cases where the Markush group was held improper include Ex Parte Palmer, 7 USPQ 11, In re Winnek, 73 USPQ 225, In re Ruzicka, 66 USPQ 226, Ex parte Hentrich, 57 USPQ 419, Ex parte Barnard, 135 USPQ 109, Ex parte Reid, 105 USPQ 251, Ex parte Sun and Huggins, 85 USPQ 516, In re Thompson and Tanner, 69 USPQ 148, In re Swenson, 56 USPQ 180, and In re Kingston, 65 USPQ 371.
Indeed, as was stated in Ex parte Haas, 188 USPQ 374, “The rejection of a claim as containing an improper Markush grouping has a relatively long history in Office practice. The Court of Customs and Patent Appeals, at least as far back as 1942, has recognized that a rejection may be based upon the Examiner's holding that the claim has an improper Markush group. See In re Swenson, 30 CCPA 764, 132 F.2d 336, 56 USPQ 180 , citing Ex parte Palmer, 398 OG 707, 1930 CD 3.”
It should be noted that in Harnish, there was a substantial structural feature from which the common use flowed and that the claimed compounds all belong to a subgenus. That is exactly what is lacking in this case, as there is no substantial structural feature when viewing the compound as a whole. The Markush grouping is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
For example the following chemical class of compounds as a whole may be obtained:
1) wherein X = CR3 and no ring formation between variables R1,3,4 (classified as substituted
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, C07D 215/00+);
2) wherein X = N and no ring formation between variables R1,3,4 (classified as substituted
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, C07D 471/00+);
This list is not exhaustive (see other possibilities of further rings formed to the compound core due to variables R1,3,4) and clearly classifying the above groups as one subgeneric group would be repugnant to scientific classification. Thus, the first requirement is not met as described above. Secondly, there is little evidence provided that the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
The examiner recommends that the claims should be amended to include only species that share a single structural similarity and a common use (e.g. drawn to compounds of the formula IIb wherein X = CR3 and no ring formation between variables R1,3,4 ) to overcome the rejection.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 6-8, and 26 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The skilled artisan would not have adequate reason to believe that Applicant had possession of the claimed formula IIb shown in claim 1 based on the information provided in the specification. Note that the scope of the claimed compounds vary in the millions consisting of unknown rings systems and other functional groups which are not viewed as equivalents in the art. The only working examples described in the specification consists of the following (note that the amines attached to the cyclen have been omitted for clarity but are shown at FIG. 23B) :
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This scaffold is very defined but yet limited where minor deviations occur at variable L (alkylene group optionally comprising a phenyl group). No where does the specification allude to other working embodiments outside the scope of what is shown here. Thus, how would one skilled in the art expect that Applicant was indeed of possession of the claimed genus if only a few working embodiments were presented in the disclosure? Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p). Note also the following:
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.
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A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation.
The courts have applied this criteria in a more recent decision stating the following referencing genus claims drawn to chemical compounds:
“For example, a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” see Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010).
Therefore, based on the lack of working examples, nature of the described genus, and indefiniteness of the claims (see rejections herein), Applicants are not in possession of the claimed genus.
Claims 1, 6-8, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for compounds wherein W2 = cyclen comprising an amine, L = alkylene optionally comprising phenyl, and the combination of variable A and remaining molecule is ciprofloxacin (see Fig. 5A), does not reasonably provide enablement for the full scope of the claims. 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 use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444. Analysis is described below:
(A) Breadth of claims: The formula IIb is drawn to a myriad of substituents that vary independently and lead to compounds of a wide variety of structures. These compounds encompass molecules that widely vary in the physical and chemical properties such as size, molecular weight, acidity, basicity, and properties that are known in the art to greatly influence pharmacokinetic and pharmacodynamic parameters, not to mention the ability to productively bind to claimed biological target molecules. The claims cover compounds easily in the millions given the number of possible rings, ring systems covered by the claims' scope along with varying choices for remaining variables; thus the claims are very broad.
(B) The nature of the invention:
(C) State of the Prior Art: Chemistry is unpredictable. See In Re Marzocchi and Horton 169 USPQ at 367 paragraph 3:
"Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why. Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task.
In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work ......Chemists tend not to publish negative results, because these are, as opposed to positive results, never definite (and far too copious)" Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface.
(D) Skill of those in the art: The level of skill in the art is high.
(E) Level of predictability in the art: It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(F) Direction or Guidance: Little guidance or direction is provided by applicant in reference to making and mostly using compounds other than the limited examples stated herein. The presence of various bulky heterocyclic or carbocyclic rings attached to the compound’s core may be chemically incompatible with the method of use embraced in the instant claims. Specification offers no teachings or suggestion as to how to make and use these compounds. Also, note MPEP 2164.08(b) which states that claims that read on "... significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.";
(G) Working Examples: The compound core depicted with specific substituents represent a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds where the compound of formula IIb did not contain the variables previously mentioned above in the present application.
The specification gives some antibacterial test results on of a limited number of preferable compounds, however it is too homogeneous to provide a clear evaluation of which moieties attached to the compound’s core out of the many claimed might affect potency to a large or small degree. The pharmaceutical art is unpredictable and target compounds need to be individually assessed for viability. Extremely broad generalizations as found in the instant claims are in contradiction with the basis of quantitative structure-activity-relationship (QSAR).
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
(H) The quantity of experimentation needed: Since there are very limited working examples as described above, the amount of experimentation is expected to be high and burdensome. Applicant fails to provide guidance and supporting information for how to make and/or use the thousands of other compounds which are encompassed by the claims, therefore undue experimentation would be expected.
Due to the level of unpredictability in the art, the very limited guidance provided, and the lack of working examples, the applicant has shown lack of enablement. MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN E MCDOWELL whose telephone number is (571)270-5755. The examiner can normally be reached on 8:30-6 MF.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN E MCDOWELL/Primary Examiner, Art Unit 1624
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