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
Claims 1-22 are currently pending in the instant application. Claims 1-4 and 10-17 are rejected and claims 5-9 and 18-20 are withdrawn from consideration in this Office Action.
I. Priority
The instant application is a CON of 17/249,332 PAT 11,827,624 which claims benefit of US Provisional Application 62/981,767, filed on February 26, 2020.
II. Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 17, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
III. Restriction/Election
A. Election: Applicant's Response
Applicants' election with traverse of Group I in the reply filed on July 22, 2026 is acknowledged. The traversal is on the ground(s) that: it has not been shown that examining all of the claimed subject matter together would impose a serious burden.
All of the Applicants' arguments have been considered but have not been found persuasive. It is pointed out that the restriction requirement is made under 35 U.S.C. 121. 35 U.S.C. 121 gives the Commissioner (Director) the authority to restrict applications to several claimed inventions when those inventions are found to be independent and distinct. The Examiner has indicated that more than one independent and distinct invention is claimed in this application and has restricted the claimed subject matter accordingly.
Applicants argue that the restriction requirement did not show that examining all of the claimed subject matter together would impose a serious burden. However, the Examiner wants to point out that restriction showed that 1) the compounds in Group I are classified in various subclasses of class C07D 233, 403, 493, etc.(see page 3) which would be a search burden because the various inventions would require a different field of search (see page 4 and 7). Also, the restriction stated that the species on pages 30-31 are patentably distinct because these species have mutually exclusive characteristics and are not obvious variants of each other. For example, the compound
PNG
media_image1.png
120
435
media_image1.png
Greyscale
and the compound
PNG
media_image2.png
151
410
media_image2.png
Greyscale
are not obvious variants and would be classified in different subclasses of C07D because the first compound has two 5-membered nitrogen containing heteroaryl rings present whereas the second compound has one 5-membered nitrogen containing heteroaryl ring and a polycyclic ring system with oxygen heteroatoms. As stated in the restriction on page 4,
PNG
media_image3.png
224
667
media_image3.png
Greyscale
.
Each of the Class C07D 403/12; C07D 233/90; C07D 493/10, etc. encompasses numerous patents and published applications. For instance, Class C07D 403/12 contained 17,014 patents and published applications. Therefore it would constitute a burden on the Examiner and the Patent Office's resources to examine the instant application in its entirety. For the reasons stated above and those stated in the restriction, both the restriction requirement and the species election are deemed proper and made final.
Subject matter not encompassed by elected Group I are withdrawn from further consideration pursuant to 37 CFR 1.142 (b), as being drawn to nonelected inventions.
B. Status of the Claims
i. Scope of the Search and Examination of Elected Subject Matter
PNG
media_image4.png
176
667
media_image4.png
Greyscale
The above structure is the provisional elected species.
ii. Extended Prior Art Search M.P.E.P. §803.02
Following election, the Markush-type claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. If the Markush-type claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush-type claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration. On the other hand, should the examiner determine that the elected species is allowable, the examination of the Markush-type claims will be extended. If prior art is then found that anticipates or renders obvious the Markush-type claim with respect to a nonelected species, the Markush-type claim shall be rejected and claims to the non-elected species held withdrawn from further consideration. The prior art search, however, will not be extended unnecessarily to cover all nonelected species.
As indicated above, Examiner searched the compound based on the elected species, above, in response to the requirement to restrict the products of Formula (I), wherein: there was no prior art of record that anticipated or rendered obvious the elected species and therefore the scope of the subject matter was extended or broadened in pursuant to M.P.E.P. § 803.02.
The prior art search was extended to include the products of the formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
in claims 1-4 and 10-17 wherein:
L1 is a linker group;
L2 is a linker group;
R is a target binding domain (TBD).
As stated in M.P.E.P. § 803.02 , the search was extended to the species that share a single structural similarity but has not extended the search to compounds that do not share a substantial structure feature which are the compounds of formula I
PNG
media_image6.png
114
302
media_image6.png
Greyscale
excluding the compounds having formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
.
iii. Non-elected Subject Matter Withdrawn 37 C.F.R. §1.142(b)
The non-elected subject matter withdrawn are the compounds of formula
PNG
media_image6.png
114
302
media_image6.png
Greyscale
excluding the compounds having the formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
,
L1 is a linker group;
L2 is a linker group;
R is a target binding domain (TBD).
IV. Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 1-4 and 10-17 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 applicant regards as the invention. Specifically, the term “linker groups” and the phrase “a target binding domain” render the products indefinite as the term “linker groups” and the phrases “a target binding domain” “a detection moiety domain” can be considered open-ended language when not clearly defined and therefore is including additional subject matter in the compounds of the formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
that is not described in the instant specification and is not particularly pointed out or distinctly claimed. One of ordinary skill in the art would not know what structures are included and/or excluded by the term “linking groups”, “a target binding domain” or “a detection moiety domain”. Therefore the claims are considered indefinite. A claim to a chemical compound cannot be open-ended, but must be claimed with precision. This rejection can be overcome by amending the phrase amending the term “linking groups” to include the structures that are included in the term. For example, Applicants have provided what the linking groups are for L1 and L2 in claim 15. These structures should be incorporated into claim 1. Applicants are suggested to amend the phrase “a target binding domain (TBD)” to include the structures that are included in the phrase. For example, Applicants have provided what groups are included in the phrase “a target binding domain” in claim 12. These structures should be incorporated into claim 1. Applicants are suggested to amend the phrase “a detection moiety domain (DMD)” to include the structures that are included in the phrase. For example, Applicants have provided what structures are included in the phrase “a DMD” in claim 9. Applicants are suggested to incorporate this structure into claim 1.
Claim Rejections - 35 USC § 112
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.
Claims 1-4 and 10-17 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 of the formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
, does not reasonably provide enablement for the full scope of the compounds of the formula
PNG
media_image6.png
114
302
media_image6.png
Greyscale
. 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.
The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8USPQ2s 1400, 1404 (Fed. Cir. 1988). MPEP 2164.01(a) states “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”. The factors are applied below to the instant claims.
The breadth of the claims
Compounds not supported by the disclosure are the compounds of formula
PNG
media_image6.png
114
302
media_image6.png
Greyscale
excluding compounds having the formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
,
.
The nature of the invention
The compounds are disclosed to be covalent immune recruiter compounds. An alternate utility is neither disclosed in the specification nor known in the art for this genus of compounds.
The state of the prior art/level of ordinary skill/level of predictability
The level of ordinary skill is high, but the level of predictability in the art is low. Although SAR studies are not available for the instantly claimed genus of compounds, these studies have been disclosed for other compounds with the same utility, see example below.
Spiegel et al., US Patent No. 9,296,708 (eg. Table 1):
PNG
media_image7.png
507
414
media_image7.png
Greyscale
As seen above in table 1, it seems that having DNP at a terminal end of the compound is important for having a more potent activity.
It is not known what structural limitations are required for preservation of activity within the genus. In view of the low level of predictability one of ordinary skill would not know what structural modifications within the unrepresented genus (ie. unrepresented by the disclosure), if any, would lead to compounds that are active.
The amount of direction provided by the inventor/existence of working examples
Direction and working examples are limited to the genus of compounds that have adequate written description support which are the compounds of formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
. Applicants have only shown how to clearly make and use this subgenus of compounds in the specification (See pages 50-76). The following are Applicants species that have been prepared and shown to have activity:
PNG
media_image8.png
156
426
media_image8.png
Greyscale
(I-1);
PNG
media_image9.png
141
353
media_image9.png
Greyscale
(I-2);
PNG
media_image10.png
181
358
media_image10.png
Greyscale
(I-3);
PNG
media_image11.png
196
383
media_image11.png
Greyscale
(I-4);
PNG
media_image12.png
177
681
media_image12.png
Greyscale
(I-5) which all fall within the scope of
PNG
media_image5.png
217
687
media_image5.png
Greyscale
.
The quantity of experimentation needed to make or use the invention
It is not known which of the unrepresented compounds meet the structural requirements for activity. Thus, one of ordinary skill would not be enabled by the disclosure to make/use the full scope of the claimed covalent immune recruiter compounds. The amount of experimentation needed to practice the invention is undue. Further, absent an alternate utility, one of ordinary skill would not be enabled to use the compounds within the genus that are not adequately supported in the disclosure.
To overcome the rejection, Applicants are suggested to amend the claims to read on the compounds of formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
.
Claim Rejections - 35 USC § 112(a) (written description)
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.
Claims 1-4 and 10-17 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain 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, at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a compound of the formula
PNG
media_image13.png
84
313
media_image13.png
Greyscale
and compositions thereof for which the specification does not provide an adequate written description to convey that the inventors were in possession of the full scope of the claimed compounds.
MPEP § 2163 states the following:
Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). []
[D]escribing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed.[]
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." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.)
Factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163.
Partial Structure
The specification discloses 5 examples of compounds having the formula
PNG
media_image13.png
84
313
media_image13.png
Greyscale
PNG
media_image14.png
354
683
media_image14.png
Greyscale
. See, e.g., pages 30-31. Some of examples have the following structural characteristics:
PNG
media_image15.png
440
747
media_image15.png
Greyscale
PNG
media_image16.png
622
756
media_image16.png
Greyscale
, etc.
Physical/Chemical Properties and Functional Characteristics
The claimed compounds are covalent immune recruiter compounds for use in provoking an immune response to a cell. All of the compounds that were prepared and tested have the core structure
PNG
media_image17.png
211
679
media_image17.png
Greyscale
wherein R is a TBD that is
PNG
media_image18.png
231
634
media_image18.png
Greyscale
See pages 30-31.
, which has been shown to be important for activity by the data provided by Applicants in the specification. Applicants have failed to provide activity data for any compounds outside of the above structure and variable ABD, ALD or R. For example, Applicants have failed to show that if ABD is another structure such as
PNG
media_image19.png
821
686
media_image19.png
Greyscale
will the compounds maintain its covalent immune recruiter activity as seen with the scope of compounds that have been specifically tested in the specification.
Method of Making the Claimed Invention
Applicants have only provided methods of preparing the species CIR1, CIR2, CIR3, CIR4 and CIR5 in the specification. The following scheme 1 is an example what has been provided in the specification:
PNG
media_image20.png
384
730
media_image20.png
Greyscale
PNG
media_image21.png
553
761
media_image21.png
Greyscale
. Applicants have not provided a method of preparing the full scope of the compounds of formula I in the specification.
Conclusion
A reasonable structure-function correlation has not been established in the prior art for the claimed groups, which possess a high degree of structural variation. A person of ordinary skill in the art cannot reasonably predict whether a particular compound that does not have the structure
PNG
media_image22.png
110
289
media_image22.png
Greyscale
wherein A is selected from the group consisting of
PNG
media_image23.png
341
430
media_image23.png
Greyscale
.
, would be able to be used as LOX or LOX2 inhibitors since the only compounds tested have the above structure with the specific definition of variable A.
The structure/activity relationship (SAR) for binding and activity is elucidated upon analysis of IC50 data of multiple compounds with various types of structural modifications. These types of studies provide insight into the structural limitations that are required for activity, i.e. specific structural elements tolerated for the claimed activity. In the absence of such correlation, it is not possible to determine what structural modifications will allow for the preservation of the desired activity.
In conclusion: (i) substantial structural variation exists in the genus/subgenus embraced by claims 1-4 and 10-17; (ii) disclosure of species supporting genus is limited to compounds reduced to practice, which scope is not commensurate with the scope of genus/subgenus claimed; (iii) common structural attributes of the claimed genus/subgenus, combined with a correlation between structure and function, is neither disclosed in the instant application nor commonly known in the art. Thus, the specification fails to provide adequate written description for the genus of compounds of formula
PNG
media_image17.png
211
679
media_image17.png
Greyscale
claimed and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention. To overcome the rejection, Applicants are suggested to amend claim 1 so that the compounds have the formula
PNG
media_image17.png
211
679
media_image17.png
Greyscale
and not the formula
PNG
media_image24.png
65
253
media_image24.png
Greyscale
as defined in claim 1 which does not have full support in the specification. Applicants could also amend the variables in claim 1 so that the compounds of formula I read on the scope of the formula
PNG
media_image17.png
211
679
media_image17.png
Greyscale
to overcome the rejection.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-4 and 10-17 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,827,624. Although the conflicting claims are not identical, they are not patentably distinct from each other because:
Applicants claim
PNG
media_image25.png
499
734
media_image25.png
Greyscale
Determining the Scope and Content of the Issued Patent
Claim 1 of the issued patent claims
PNG
media_image26.png
705
519
media_image26.png
Greyscale
Ascertaining the Differences Between the Instant Application and the Issued Patent
The instant application claims a broader genus compound that encompasses the narrower genus of the issued patent.
Finding Prima Facie Obviousness
The genus compound of the instant application encompasses the narrower genus compound of the patented claims 1-15. The scope of the compounds in the patented claims 1-15 and the scope of the claims 1-4 and 10-17 of the instant application overlap and include patented subject matter in the instant claims. The species in issued patent’s claim 3 reads on the instant claimed genus and further, the elected species in the instant application is found in issued patent’s claim 3. Therefore, one of ordinary skill in the art would be motivated to prepare and claim the scope of the compounds in the issued patent again in the instant application since the scope already patented falls within the full scope of the instant claims 1, 2 and 7. As a result, the claims are rejected under obviousness-type double patenting.
***The closest prior art is US 9296708 which teaches compounds such as
PNG
media_image27.png
118
375
media_image27.png
Greyscale
that are used for the recruitment of antibodies to cancer cells. The prior art differs from the instant compounds of formula
PNG
media_image5.png
217
687
media_image5.png
Greyscale
by having a triazole ring instead of a diazole ring bonded to -C(=O)-O as seen in the instant compounds.
V. Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shawquia Jackson whose telephone number is 571-272-9043. The examiner can normally be reached on 6:30 AM-3:00PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Adam Milligan can be reached on 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SHAWQUIA JACKSON/Primary Examiner, Art Unit 1626
Prosecution Insights