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 .
Information Disclosure Statement
The information disclosure statement filed on August 14, 2023 is acknowledged and has been considered by the examiner.
Providing reference citations in the body of the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the office and MPEP § 609.04(a) states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references found in the body of the specification have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the terms CHIRALPAK and ORIGINPRO, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities:
In the structure of 2C013 provided on page 33 of the specification, there are empty rectangular boxes in both the structure and chemical formula. Based on the other related structures, it appears that all nitrogen atoms have been replaced by the rectangles.
In the Brief Description of the Figures on page 43 of the specification, there is a recitation of “Error! Reference source not found.” preceding what might be the caption for Figure 3 (no clearly defined caption for Figure 3 is provided in the current state of the document).
Appropriate correction is required.
Claim Interpretation
Claims 1-9, 11-12, and 16 claim structures and “any individual isomer thereof.” Regarding the stereoisomer subset of isomers, these claims depict a varying number of chiral centers in specified R or S configurations. These claims also provide structures in which the configuration of some chiral centers is not specified. It is interpreted that “any individual isomer thereof” includes stereoisomers of the claimed compounds at any chiral center in the provided structures, including both pre-specified and unspecified chiral centers.
Claims 1-9, and 11-12 recite the phrase “chelator moiety, optionally containing a chelated nonradioactive or radioactive cation.” As this limitation is optional, it means that this limitation is not a requirement of the claim and art that does not teach this limitation while teaching the other limitations will read on the claim.
Claims 1-5, 7-8, 11, 16-17, and 19 recite the phrase “the fluorine atom is optionally 18F.” As this limitation is optional, it means that this limitation is not a requirement of the claim and art that does not teach this limitation while teaching the other limitations will read on the claim.
Claims 16-17 recite the phrase “the compound optionally contains a chelated nonradioactive or radioactive cation.” As this limitation is optional, it means that this limitation is not a requirement of the claim and art that does not teach this limitation while teaching the other limitations will read on the claim.
The SIFA structures provided in claims 1-3 are interpreted as complete structures with all atoms and their connections specified. Analyzing the structures under the standards for depictions of organic chemistry structures, it is interpreted that attached to the amide nitrogen are a carbonyl group, a hydrogen, and an ethyl group.
Regarding claims 23 and 24, the applicant claims a method of imaging, treating, and/or diagnosing cancer. The applicant also defines on page 29 of the instant specification that “The term ‘treatment’ in relation to the uses of any of the compounds described herein … is used to describe any form of intervention where a compound is administered to a subject suffering from, or at risk of suffering from, or potentially at risk of suffering from the disease or disorder in question. Thus, the term ‘treatment’ covers both preventative (prophylactic) treatment and treatment where measurable or detectable symptoms of the disease or disorder are being displayed.” MPEP §211.01 states “Where an explicit definition is provided by the applicant for a term, that definition will control interpretation of the term as it is used in the claim.” Thus, claims 23 and 24 are interpreted to include both methods of prophylactic (prevention) and therapeutic (treating an already established cancer) cancer treatments in their scopes.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 11-16, 18, 21, and 23-24 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-9, 11-16, 18, 21, and 23-24 are drawn to compounds (or the use thereof) described with structures in the claim set and “any individual isomer thereof.” In chemistry, an isomer is a species having the same atomic composition but a different 3-dimensional structure. There are several classes of isomers, including structural isomers (in which the atoms are connected in different ways such that different connections are present) and stereoisomers (in which the atoms are connected to the same neighbors by the same type of bonds but differ in their relative positions in space). The instant specification provides adequate written description for stereoisomers of chiral atoms but does not provide adequate disclosure of structural isomers or other types of isomers or the use thereof. Therefore, the claim scope encompasses subject matter which was not sufficiently described in the specification.
Claims 1-3, 13-15, 18, 21, and 23-24 are drawn to compounds (and the use thereof) in which one of the R groups may be a SIFA moiety in which there is an ethyl group attached to the nitrogen (see Claim Interpretation). While the specification states that structures in which this form of the SIFA group are an aspect of the invention (e.g., page 7), no complete structures provided in the specification, examples, or drawings include two carbons between the SIFA moiety nitrogen and the linker region of the molecule. Therefore, there is insufficient disclosure of compounds containing this ethyl region in the SIFA moiety or the use of such compounds. Based on the preponderance of evidence in the claims dependent on claims 1-3 providing more specific structures and the description of the invention in the specification, these claims will be examined under the interpretation that there is to be one carbon between the SIFA amide nitrogen and the linker group.
Claims 23 and 24 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 imaging, diagnosing, and therapeutically treating cancer, does not reasonably provide enablement for prophylactic treatment (prevention) of cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. These factors include, but are not limited to:
The breadth of the claims;
The nature of the invention;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427, F.2d 833, 839, 166 USPQ 18, 24 (1970). To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level
The invention of claims 23 and 24 relates to methods of imaging, diagnosing, therapeutically treating, and prophylactically treating cancer. This method comprises administering the compound of claim 1 to a patient in need thereof.
The relative skill of those in the art who would practice this method is high, likely that of a one who has obtained a PhD or MD.
In the art, it is known that PSMA is a biomarker connected to several cancers and that PSMA ligands can effectively bind to PSMA.
Successful disease prevention (prophylaxis) is much less predictable than therapeutic treatment of an already established disease or disorder. Enrichment of a biomarker like PSMA at a site of disease tends to mean that molecules that selectively bind to the biomarker will become enriched at that site upon administration. Thus, therapy, imaging, and diagnosing for the claimed cancers of claim 24 seem enabled, as PSMA may play a role in or be a marker for each of these cancers. However, it is not clear that PSMA is an effective preemptive susceptibility/risk biomarker (enriching at site of disease prior to the establishment of the disease state) for the claimed cancers. Even if it was, it is not predictable whether early PSMA targeting would prevent the development of the claimed cancers.
The breadth of the claims
The claims are broad insofar as the method encompasses therapy, prophylaxis, imaging, and diagnosis. These medical interventions are different and are often performed by different specialized practitioners. Additionally, the claims encompass administration to patients both suffering from cancer and those who have yet to develop cancer. Multiple cancers with different pathophysiology are claimed.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides little direction or guidance for practicing the claimed invention in its “full scope.” Working examples are provided for administration of [177Lu]2C011, [177Lu]Lu-2C013, [177Lu]2C014, and [177Lu]2C015 to LNCaP tumor-bearing male CB-17 SCID mice for biodistribution and imaging studies. These examples teach the administration of the compound to mice and enrichment of the compound at a xenograft tumor. No direction or guidance is provided for cancer prevention. No evidence of efficacy of any compounds for either therapeutic or prophylactic treatment is provided.
The quantity of experimentation necessary
Experimentation to determine a therapeutically or diagnostically effective amount of material to administer to a subject can be significant. Furthermore, determining if any given compound is effective for the prevention of a disease is more significant and often spans longer periods of time. Rigorous prevention studies would require large cohorts and a long time horizon of observations to monitor disease occurrence in treatment and comparison groups. Further experimentation to provide evidence that the intervention is the primary cause of any observed cancer prevention would additionally be complex.
Because of the known unpredictability of the art, and in the absence of experimental evidence and working examples, it is difficult to determine the amount of experimentation required to determine an effective way to use the compound of claim 1 for the prevention of cancer.
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the claimed invention in its “full scope,” a person of ordinary skill in the art would have to engage in an unreasonable amount of experimentation, with no reasonable expectation of success.
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 1-9, 11-16, 18, 21, and 23-24 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.
Claims 1-3 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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 relationship is the attachment point between the SIFA moiety and the linker region. While the provided R1 and R2 groups branching off the linker chain denote the location on the linker chain where the SIFA group would attach, the attachment point on the SIFA structure is absent. As the claims are currently written, it is not clear what atom(s) of the SIFA group may connect to the linker region. Thus, claims 1-3 are indefinite. Furthermore, claims 13-15, 18, 21, and 23-24 are rejected due to their dependence on claims 1-3. Claims 4-12, 16-17, and 19 depend on claims 1-3 but also contain further limitations that define the SIFA-linker attachment points and are thus not indefinite for this reason. For the purpose of examining, the attachment point on the SIFA group will be interpreted to be on any atom of the SIFA group.
Claims 1-9, 11-16, and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for failing to particularly point out and distinctly claim the invention. All of these claims are drawn to compounds having structures provided in the claim document and “any individual isomer thereof.” As discussed above, the term isomer includes several classes of isomers, including structural isomers (see related 112(a) rejection). Considering the number of atoms in the claimed structures, the number of potential structural isomers is exceedingly high. Furthermore, the majority of these structural isomers would not have the same function as the provided structures, as the PSMA, SIFA, and chelator regions are not present in most possible structural isomers of the claimed compounds. Thus, it is not clear what structures are actually being claimed, rendering the claims indefinite. Furthermore, claims 21, 23, and 24 are rejected due to their dependence on these claims. While claims 10, 17, and 19 depend on these claims, they do not have claim scopes encompassing structural isomers and are therefore not rejected. For the purpose of examination, “isomer” will be interpreted to refer to stereoisomers related to the chiral centers of the provided structures.
Claims 14 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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 relationship is the attachment point between the specifically listed chelator moiety groups and the linker region. While the provided CM on claim 1 denotes the location on the linker chain where the chelator moiety would attach, the attachment point on the chelator moieties is not specified in the claim. As the claims are currently written, it is not clear what atom(s) of the listed chelator moieties may connect to the linker region. Thus, claims 14 and 15 are indefinite. For the purpose of examination, the scope of the attachment between the linker and chelator will be interpreted to be any attachment via a bond between the nitrogen connected to the CM symbol of structure 1c in claim 1 to any atom of the listed chelator groups.
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 4-5, 7-8, 10-11, 16-17, and 19 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 claims upon which they depend, or for failing to include all the limitations of the claims upon which they depend.
Regarding claims 4, 7, 10, 16-17, and 19, these claims depend on claims 1-3, which claim structures in which there is an ethyl group attached to the nitrogen of the SIFA moiety (see Claim Interpretation). However, the structures of these claims only have a single alkyl carbon between the nitrogen and the linker group attachment point. Therefore, these claims fail to include all the limitations of the claims upon which they depend.
Regarding claims 5 and 8, these claims depend on claims 4 and 7, respectively. Claims 4 and 7 are drawn to specific provided structures with some specified chiral centers and the claimed scope encompasses “any individual isomer thereof.” Claims 5 and 8 depict structures with more chiral centers specified and also claim “any individual isomer thereof.” While claims 5 and 8 provide drawn structures that are narrower in scope than the structures and language of claims 4 and 7, inclusion of the stereoisomers of claims 5 and 8 result in no change in claim scope. Therefore, these claims fail to further limit the subject matter of the claims upon which they depend.
Regarding claim 11, this claim is drawn to a structure of a compound and the scope includes “any individual isomer thereof.” Claim 10, upon which claim 11 depends, is drawn to a similar structure, but the scope of the claim does not encompass all isomers of the provided structure. While most chiral centers are drawn without specified chiral configuration in the structure of claim 10, two specified chiral centers are provided in the PSMA region of the structure. “Any individual isomer thereof” of the structure of claim 11 includes stereoisomers of the chiral carbons in the PSMA region. Therefore, claim 11 fails to retain all the limitations of the claim on which it depends.
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.
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 1-2, 4-9, 13-19, 21, and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 20 of copending Application No. 18/694,567. Although the claims are not identical, they are not patently distinct from each other for the following reasons.
Regarding instant claims 4-6, 16-17, and 19, conflicting claims 9 and 20 of the copending application include a limitation of the compound of formula (1c). The compound of formula (1c) has a structure that anticipates the compounds claimed in instant claims 4-6, 16-17, and 19.
Regarding instant claims 1-2,13-15, 18, 21, and 23-24, conflicting claims 9 and 20 of the copending application include a limitation of the compound of formula (1c). Based on the interpretation provided in a related 112(a) written description rejection above, the examiner is interpreting the structures of instant claims 1-2, 13-15, 18, 21, and 23-24 to require there to be one carbon between the SIFA amide nitrogen and the linker group. Under this interpretation, the compound of formula (1c) of the reference application has a structure that anticipates the compounds of instant claims 1-2, 13-15, 18, 21, and 23-24. If this interpretation is incorrect, the compound of formula (1c) differs from the compounds of instant claims 1-2, 13-15, 18, 21, and 23-24 only in that there is just one carbon between the SIFA group and the linker in the conflicting claims, whereas the instant claims in their current form require two carbons between the SIFA amide nitrogen and the linker (see Claim Interpretation section). While the copending application does not claim the exact structure as the instant application, an alkyl chain with a length of one carbon is an obvious homolog with similar properties to an alkyl chain of two carbons. Compounds which are homologs are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP § 2144.09). Thus, the structure (1c) of the conflicting claims render instant claims 1-2, 13-15, 18, 21, and 23-24 obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612