DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending.
Status of Priority
The present application claims the benefits of priority to U.S. Provisional Application No. 63/588,038, filed on October 5, 2023.
Specification - Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
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.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Information Disclosure Statement
The instant application is accompanied with no IDS. Examiner would like to remind Applicant that “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section. The duty to disclose information exists with respect to each pending claim until the claim is cancelled or withdrawn from consideration, or the application becomes abandoned. Information material to the patentability of a claim that is cancelled or withdrawn from consideration need not be submitted if the information is not material to the patentability of any claim remaining under consideration in the application. There is no duty to submit information which is not material to the patentability of any existing claim. The duty to disclose all information known to be material to patentability is deemed to be satisfied if all information known to be material to patentability of any claim issued in a patent was cited by the Office or submitted to the Office in the manner prescribed by §§ 1.97(b) -(d) and 1.98. However, no patent will be granted on an application in connection with which fraud on the Office was practiced or attempted or the duty of disclosure was violated through bad faith or intentional misconduct.” See 37 C.F.R. 1.56 for more details.
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.
Written Description
Claims 1-20 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.
The specification does not adequately describe the structural diversity of the claimed Gαi2 inhibitor compound genus
Currently, the claims are broad insofar as the instant claims recite a compound of instant formula I wherein the compound can possess a structurally diverse range of chemical substituents at the R4 position.
The method claims of claims 1-15 are also broad insofar as they encompass administering a chemotherapeutic drug of any structure and a Gαi2 inhibitor of any structure to a subject with a cancer of any type. In other words, the instantly claimed methods of claims 1-15 also encompass administering a Gαi2 inhibitor that is currently not established as being a Gαi2 inhibitor, but may be discovered to be a novel Gαi2 inhibitor upon future scientific investigations.
The method claims of claims 16-20 are also broad insofar as they encompass a method of reducing the migration of any cell type in a subject that is receiving a chemotherapeutic drug of any structure (specifically, a chemotherapeutic drug that inhibits cancer cells of any type), the method comprising administering a Gαi2 inhibitor of any structure. In other words, the instantly claimed methods of claims 16-20 also encompass administering a Gαi2 inhibitor that is currently not established as being a Gαi2 inhibitor, but may be discovered to be a novel Gαi2 inhibitor upon future scientific investigations.
Although the instant claims are extremely broad, the instant specification only provides limited working examples.
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor 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.’ 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).
The instant specification only provides 38 specific examples of compounds encompassed by instant claims 2 and 17 (see pg. 15-18 for structures) and teaches the synthesis of exemplifying compounds (see pg. 22-26 and pg. 28-29). These examples do not adequately represent the full breadth of the claimed genus which was established to be broad. For example, according to instant claims 2 and 17, the compound of Formula I can possess many different structurally diverse substituents at the R4 position. However, in the instant case, all 38 specific examples possess the following structural features:
R4 = H.
Note: some of the compounds of the instant specification are previously disclosed in Khan (WO2022140297A1; published June 30, 2022) which also only discloses specific compounds wherein the R4 position is only occupied by a H atom. As such, significant portions of the claimed structural space remain unexplored by the specific examples provided in the instant case and in the prior art (i.e., Khan). According to MPEP § 2163 (see above), a narrow subgenus of compounds (i.e., in this case, wherein R4 = H) does not adequately reflect a claimed genus that is structurally diverse (i.e., as claimed: R4 = H, alkyl, halo-alkyl, aryl, pyridyl, wherein the aryl and pyridyl groups are optionally substituted with any substituent at the ortho, meta, and para positions). Accordingly, the disclosed species do not adequately reflect the structural diversity of the claimed genus and do not demonstrate possession of the full scope of compounds recited in instant claims 2 and 17.
Furthermore, merely identifying a limited number of Gαi2 inhibitors in the instant specification (which is also disclosed in the prior art, Khan) does not adequately describe the structural diversity encompassed by the claimed genus of “G(alpha)i2 (Gαi2) inhibitor” and “Gαi2 inhibitor” recited in claims 1 and 16, respectively. The claims are not limited to compounds sharing a common chemical scaffold or structural motif, but instead encompass the entire class of Gαi2 inhibitor compounds without identifying structural characteristics representative of that genus or otherwise demonstrating possession of its full scope.
Moreover, the prior art itself recognizes that membership in a pharmacological class does not establish that all compounds within that class possess the same therapeutic properties. As explained by Furberg (Furberg, C. D. Class Effects and Evidence-Based Medicine. Clin. Cardiol. 2000, 23, pg. IV-15 to IV-19.):
“Drugs grouped into a therapeutic class on the basis of a common mechanism of action often have considerably different pharmacodynamic and pharmacokinetic properties” (abstract, 1st sentence);
“Equipotency in terms of clinical efficacy is difficult to determine. Since the concept of “class effect” is a term of convenience that has no universally accepted definition and subsequently should not form the basis for the practice of evidence-based medicine, untested drugs of a “class” should be considered to be unproven drugs” (abstract, last two sentences).
Accordingly, a POSITA would have understood that evidence relating to one or a limited number of Gαi2 inhibitors possessing the same core structure does not establish that all compounds within the class possess the same utility for reducing cancer cell migration. Although the prior art, Khan, discloses specific Gαi2 inhibitors of the instant invention having the capability of reducing prostate cancer cell migration, the specification does not reasonably convey that the inventor was in possession of the full claimed genus of:
a method comprising:
administering, to a subject with cancer, a chemotherapeutic drug under conditions effective to treat the subject for cancer; and administering, to the subject, a G(alpha)i2 (Gαi2) inhibitor of any structure; and
a method of reducing cell migration in a subject that is receiving a chemotherapeutic drug to inhibit cancer cells, the method comprising administering a Gαi2 inhibitor of any structure.
Rather, the disclosure relies on the common functional characteristic of Gαi2 inhibition and extrapolates the asserted therapeutic utility to the entire class without identifying other distinguishing characteristics demonstrating possession of the full scope of the claimed genus.
Functional definition of the claimed compound genus does not demonstrate possession
Additionally, the recitation of “G(alpha)i2 (Gαi2) inhibitor” and “Gαi2 inhibitor” recited in claims 1 and 16, respectively, creates a “reach-through” aspect to the claim. Specifically, the claims are not limited to compounds presently recognized as being Gαi2 inhibitors, but, instead, potentially reaches through to novel compounds that may later be discovered to function as a Gαi2 inhibitor. Thus, the scope of the claims is not confined to the Gαi2 inhibitors represented by instant Formula I, but extends to novel Gαi2 inhibitors identified only through future scientific investigation. However, the instant specification does not reasonably convey possession of such a broad genus. The limited number of specific Gαi2 inhibitor compounds referenced in the instant specification does not provide a representative disclosure or identify structural features common to the claimed compound genus sufficient to demonstrate possession of the full scope of “Gαi2 inhibitor.” Accordingly, the “reach-through” scope of the claim further demonstrates that the instant specification does not reasonably convey possession of the full scope of “G(alpha)i2 (Gαi2) inhibitor” and “Gαi2 inhibitor” as presently claimed in claims 1 and 16, respectively.
Lack of written description support for the full scope of cancer types and chemotherapeutic drugs
The instant specification also fails to demonstrate possession of the full scope of the claimed therapeutic methods. The instant specification demonstrates that selected Gαi2 inhibitors encompassed by instant Formula I with selected chemotherapeutic drugs have the capability to reduce prostate cancer cell migration (wherein the migration is caused by the specific chemotherapeutic drug) in the context of three specific prostate cancer cell lines (see instant examples 3 and 5-9). However, the three prostate cancerous cell lines do not adequately represent the broad genus of cancers/cancer cells encompassed by instant claims 1-20. Note: reducing cell migration in the context of three prostate cancer cell lines does not establish that the claimed genus of Gαi2 inhibitor compounds would be able to reduce the migration of cancer cells across all cancer types wherein each cancer type has a different driver and mechanism of disease progression. This is consistent with the prior art teachings as explained below:
Prior art referenced:
Zhong et al. (Zhong) (Zhong, M. et al. The Essential Role of Gia2 in Prostate Cancer Cell Migration. Mol Cancer Res 2012, 10, 1380-1388.),
Sun et al. (Sun) (Sun, Z. et al. Doxorubicin promotes breast cancer cell migration and invasion via DCAF13. FEBS Open Bio 2022, 12, 221-230.; first published November 14, 2021.),
Zhao et al. (Zhao) (Zhao, Y. et al. Chemotherapy exacerbates ovarian cancer cell migration and cancer stem cell-like characteristics through GLI1. British Journal of Cancer 2020, 122, 1638-1648.),
Chen et al. (Chen) (Chen, J. et al. Androgen-deprivation therapy with enzalutamide enhances prostate cancer metastasis via decreasing the EPHB6 suppressor expression. Cancer Letters 2017, 408, 155-163.), and
Liu et al. (Liu) (Liu, C.-L. et al. Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway. J Breast Cancer 2019, 22, 185-195.)
Zhong specifically teaches that their “data suggest that Gαi2 plays an essential role in prostate cancer cell migration” (pg. 1387, right col., last sentence). Thus, the prior art establishes a particular mechanistic basis for targeting Gαi2 to reduce migration in prostate cancer cells. However, this teaching does not establish that Gαi2 is an essential mediator of cancer cell migration generally, particularly where the migration is induced by a chemotherapeutic drug. Rather, the prior art demonstrates that chemotherapeutic drug-induced cancer cell migration can occur through different signaling mechanisms depending on the cancer type and the chemotherapeutic drug involved.
For example:
Sun teaches that doxorubicin promotes breast cancer cell migration and invasion through DCAF13, rather than through Gαi2 (see title) and explicitly suggests that “future therapeutics targeting DCAF13 may help reduce the risk [of metastasis of drug-resistant breast cancer cells], especially for patients undergoing chemotherapy” (see abstract, last two sentences).
Zhao teaches that chemotherapy exacerbates ovarian cancer cell migration through GLI1, rather than through Gαi2 (see title) and explicitly suggests that “[t]argeting GLI1 may improve clinical benefits in the chemotherapy-exacerbated metastasis in ovarian cancer treatment” (see abstract, last sentence).
Moreover, prior art concerning prostate cancer teaches that enzalutamide can enhance prostate cancer metastasis through decreased expression of the EPHB6 suppressor, without establishing that such migration induced by the chemotherapeutic drug is mediated through Gαi2 (see Chen, abstract). Chen even teaches that targeting the “AR/EPHB6/JNK signaling with JNK inhibitor (SP600125) may then block/reverse the Enz [i.e., Enzalutamide]-increased CRPC [i.e., castration resistant prostate cancer] cell invasion” (see abstract). Chen does not suggest that a Gαi2 inhibitor would help reduce the CRPC migration.
Accordingly, the prior art does not establish a common Gαi2-dependent mechanism by which chemotherapeutic drugs induce migration across different cancers. Instead, the art indicates that the pathways responsible for chemotherapy-induced migration can differ depending on the type of cancer and the chemotherapeutic treatment involved. Therefore, the demonstrated ability of a Gαi2 inhibitor to reduce migration in the prostate cancer models of the instant specification does not, by itself, provide a sufficient basis for predicting that Gαi2 inhibition would similarly reduce chemotherapeutic drug-induced migration in other cancers whose migratory behavior may be driven by different pathways. A POSITA therefore could not determine from the instantly disclosed prostate cancer examples alone which additional cancer types, and which chemotherapeutic drug/cancer combinations, would exhibit migration that is sufficiently dependent on Gαi2 such that administration of a Gαi2 inhibitor would reduce that migration.
As such, the instant specification does not provide adequate written description support for the full scope of the claimed method encompassing any cancer/cancer cell and any chemotherapeutic drug because the limited disclosed examples do not demonstrate that the inventors were in possession of a method applicable across these broad genus, nor does the specification identify a common characteristic or mechanism that would allow a POSITA to predict and determine which cancer and chemotherapeutic drug combinations would result in Gαi2-dependent cancer cell migration that can, therefore, be reduced by administration of a Gαi2 inhibitor.
Additionally, the unpredictability of chemotherapeutic drug-induced cancer cell migration is further demonstrated by prior art showing that even the same chemotherapeutic drug can promote migration through different mechanisms depending on the cancer model examined. For example, Liu taught that doxorubicin promotes migration and invasion of MCF7 and BT-474 breast cancer cells through the activation of the RhoA/MLC pathway (see abstract). In contrast, Sun taught that doxorubicin promotes migration and invasion of BT549 and MDA-MB-231 breast cancer cells through DCAF13 (see abstract and Fig. 5 + caption). Thus, even within breast cancer, the prior art identified different pathways associated with doxorubicin-induced migratory behavior in different cancer cell models. These teachings further demonstrate that the mechanism responsible for chemotherapeutic drug-induced migration cannot be reliably predicted merely from the identity of the chemotherapeutic drug or the general cancer type.
Accordingly, the fact that Gαi2 inhibition reduced migration in the prostate cancer models (wherein the migration is induced by a chemotherapy drug) disclosed in the instant specification does not provide a reasonable basis for concluding that Gαi2 inhibition will reduce chemotherapeutic drug-induced migration across the broad genus of cancers and chemotherapeutic drugs encompassed by the claims. Therefore, the limited examples of cancers/chemotherapeutic drugs disclosed in the instant specification do not reasonably demonstrate that the instant specification was in possession of the full claimed genus encompassing any cancer/cancer cell and any chemotherapeutic drug, particularly where the specification does not identify a common structural or functional characteristic that would allow a POSITA to determine which cancer/chemotherapeutic drug combinations would exhibit Gαi2-dependent migration and would therefore respond to administration of a Gαi2 inhibitor.
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 1-17, 19, and 20 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 term “effective” in claim 1 is a relative term which renders the claim indefinite. The term “effective” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the chemotherapeutic drug administered to the subject is rendered indefinite by the use of the term “effective.”
Claims 2-15, which are dependent on claim 1, are also rejected for further requiring and/or reciting the indefinite limitation of claim 1.
Claims 2 and 17 recite “optionally substituted” without specifying what substituents are encompassed. Neither the claim nor the specification discloses the types of substituents encompassed. Therefore, it is unclear what chemical structures are encompassed by the term “optionally substituted” as the term could include an unlimited range of functional groups and substitution patterns, including those that would significantly alter the chemical and physical properties of the claimed compound. As such, a POSITA would not be able to determine the metes and bounds of the claimed invention with reasonable certainty and claims 2 and 17 are rendered indefinite.
The limitations “G(alpha)i2 (Gαi2) inhibitor” and “Gαi2 inhibitor,” as recited in instant claims 1 and 16, respectively, render the scope of the claims indefinite because the claims define the compound only by its functional relationship to Gαi2, without:
identifying which compounds possessing which core structures are encompassed by the claims or
providing an objective standard for determining when a Gαi2 inhibitor is sufficiently inhibiting Gαi2 to fall within the scope of the claim.
It is therefore unclear whether the limitation only encompasses Gαi2 inhibitors known before the effective filing date of the claimed invention, or does it also encompass novel Gαi2 inhibitors that are not yet known and only discovered through future investigations. Therefore, “G(alpha)i2 (Gαi2) inhibitor” and “Gαi2 inhibitor,” render the boundaries of the claimed genus to be vague and indefinite.
Claims 13-15, which are dependent on claim 1, are also rejected for further requiring and/or reciting the indefinite limitation of claim 1.
Claims 19-20, which are dependent on claim 16, are also rejected for further requiring and/or reciting the indefinite limitation of claim 16.
Note on 35 USC § 102 and § 103 Rejections
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over:
Khan et al. (Khan) (WO2022140297A1; published June 30, 2022) in view of
Johns Hopkins Medicine. Chemotherapy for Prostate Cancer. Published September 16, 2019. https://web.archive.org/web/20190916224053/https://www.hopkinsmedicine.org/health/conditions-and-diseases/prostate-cancer/chemotherapy-for-prostate-cancer
Other cited references:
Caggia et al. (Caggia) (Caggia, S. et al. Small Molecule Inhibitors Targeting Gαi2 Protein Attenuate Migration of Cancer Cells. Cancers 2020, 12, 1631.) and
Yang et al. (Yang) (Yang, C. et al. Effect of docetaxel on the regulation of proliferation and apoptosis of human prostate cancer cells. Molecular Medicine Reports 2019, 19, 3864-3870.)
Khan teaches a method of using a compound of Formula I (i.e., Gαi2 inhibitors encompassed by instant Formula I) to inhibit cell migration in prostate cancer cell lines, breast cancer cell lines, and ovarian cancer cell lines (see Khan, claim 7). In particular, Khan teaches that in PC3 prostate cancer cells, compound 14 “significantly decreased EGF-induced migratory capability” (para. 00089, 2nd sentence). Khan further teaches that compound 14 reduced EGF-induced migration in DU145 prostate cancer cells (para. 00052, 1st sentence).
Note:
compound 14 of Khan (herein, referred to as Khan-compound-14; see para. 00014) has the same structure as the compound recited in instant claim 4; and
the ability of Khan-compound-14 to reduce the migration of PC3 and DU145 prostate cancer cell was first reported in Caggia (see abstract of Caggia for overview of findings).
Therefore, Khan teaches Gαi2 inhibitors and their ability to reduce cancer cell migration, including migration of prostate cancer cells.
Khan does not teach the use of a Gαi2 inhibitor as the primary treatment for prostate cancer via apoptosis. Instead, Khan teaches its use for mainly reducing cancer cell migration. Johns Hopkins Medicine does teach the use of a chemotherapeutic drug as the primary treatment for prostate cancer.
Johns Hopkins Medicine teaches that docetaxel is the most common chemotherapy drug for prostate cancer (see “Types of Chemotherapy Drugs” section, 1st sentence). Yang further teaches that docetaxel can induce apoptosis in PC3, DU145, and LNCaP prostate cancer cells, thereby further demonstrating the known anticancer activity of docetaxel against prostate cancer cells (see abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer to a subject with prostate cancer:
a chemotherapeutic drug, such as docetaxel as taught by Johns Hopkins Medicine and
a Gαi2 inhibitor of Khan.
A POSITA would have been motivated to make such a combination because docetaxel was already known and commonly used to treat prostate cancer, while Khan teaches that Gαi2 inhibitors encompassed by instant formula I reduce the migratory capability of prostate cancer cells. Accordingly, a POSITA would have had reason to administer the Gαi2 inhibitor of Khan in addition to the chemotherapeutic drug, docetaxel, because the two agents would provide complementary benefits in the treatment of prostate cancer. Specifically, while the chemotherapeutic drug would treat the prostate cancer via apoptosis or inhibition of cancer cell growth, the Gαi2 inhibitor would reduce the ability of the prostate cancer cells to migrate and potentially spread to other locations.
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 1-4 and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-6 of U.S. Patent Application No. 12,084,418 B2 (‘418B2)
Although the claims at issue are not identical, they are not patentably distinct from each other because it would have been obvious to one of ordinary skill in the art to modify the invention of the patented claims in view of the teachings of:
Johns Hopkins Medicine. Chemotherapy for Prostate Cancer. Published September 16, 2019. https://web.archive.org/web/20190916224053/https://www.hopkinsmedicine.org/health/conditions-and-diseases/prostate-cancer/chemotherapy-for-prostate-cancer
to arrive at the invention of instant claims 1-4 and 15-18.
Other cited references:
Yang et al. (Yang) (Yang, C. et al. Effect of docetaxel on the regulation of proliferation and apoptosis of human prostate cancer cells. Molecular Medicine Reports 2019, 19, 3864-3870.)
‘418B2 teaches a method of treating cancer, comprising administering to a subject in need thereof a compound of Formula I (i.e., Gαi2 inhibitors encompassed by instant Formula I) to inhibit cell migration in prostate cancer, breast cancer, and ovarian cancer (see ‘418B2, claims 4-6). In particular, ‘418B2 teaches that in PC3 prostate cancer cells, compound 14 significantly decreased EGF-induced migratory capability (col. 7, lines 39-41). ‘418B2 further teaches that compound 14 reduced EGF-induced migration in DU145 prostate cancer cells (col. 7, lines 44-45). Note: compound 14 of ‘418B2 is the same as the compound of instant claim 4.
‘418B2 does not teach the use of a Gαi2 inhibitor as the primary treatment for prostate cancer via apoptosis. Instead, ‘418B2 teaches its use for mainly reducing cancer cell migration (see abstract). Johns Hopkins Medicine does teach the use of a chemotherapeutic drug as the primary treatment for prostate cancer.
Johns Hopkins Medicine teaches that docetaxel is the most common chemotherapy drug for prostate cancer (see “Types of Chemotherapy Drugs” section, 1st sentence). Yang further teaches that docetaxel can induce apoptosis in PC3, DU145, and LNCaP prostate cancer cells, thereby further demonstrating the known anticancer activity of docetaxel against prostate cancer cells.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer to a subject with prostate cancer:
a chemotherapeutic drug, such as docetaxel as taught by Johns Hopkins Medicine and
a Gαi2 inhibitor of ‘418B2.
A POSITA would have been motivated to make such a combination because docetaxel was already known and commonly used to treat prostate cancer, while ‘418B2 teaches that Gαi2 inhibitors encompassed by instant formula I reduce the migratory capability of prostate cancer cells. Accordingly, a POSITA would have had reason to administer the Gαi2 inhibitor of ‘418B2 in addition to the chemotherapeutic drug, docetaxel, because the two agents would provide complementary benefits in the treatment of prostate cancer. Specifically, while the chemotherapeutic drug would treat the prostate cancer via apoptosis or inhibition of cancer cell growth, the Gαi2 inhibitor would reduce the ability of the prostate cancer cells to migrate and potentially spread to other locations.
Thus, the claims at issue are not patentably distinct from each other because it would have been obvious to one of ordinary skill in the art to modify the invention of the patented claims in view of the teachings of Johns Hopkins Medicine as explained above.
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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