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
1. Applicant’s amendments filed 8/17/23 and 10/25/23 are acknowledged and have been entered.
2. Ms. Bin Wang, in a voicemail message of 2/3/26, made a provisional election with regard to the method recited in instant claims 1-20 to elect the species of polypeptide corresponding to SEQ ID NO: 9 and administration of a second therapeutic agent for the purpose of initial search and examination. Applicant’s representative did not traverse the said species election. Affirmation of this election must be made by applicant in replying to this Office action. The restriction requirement appears below:
This application contains claims directed to more than one species of the generic invention. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1.
The species are as follows:
a) elect a specific species of polypeptide that is one of SEQ ID NO: 1-16 to be used in the claimed method of treating or killing an ovarian cancer; and b) In addition, elect is the polypeptide is administered in combination with a second therapeutic agent or if a second therapeutic agent is contacted to the ovarian cancer cell.
Applicant is required, in reply to this action, to elect a single species to which the claims shall be restricted if no generic claim is finally held to be allowable. The reply must also identify the claims readable on the elected species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered non-responsive unless accompanied by an election.
Upon the allowance of a generic claim, Applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. Currently, claim 1 is generic.
3. Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
3. The listing of references in 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 have been cited by the examiner on form PTO-892, they have not been considered.
4. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
5. The lengthy 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.
6. Claim interpretation: The specification discloses that “a” wild-type actinohivin is represented by SEQ ID NO: 1, and “an” actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, and was originally identified and isolated from the actinomycetes K97-0003 strain (citing IDS reference Chiba et al.)([0044] and [00198]). The specification discloses that “as used herein, the term “variant” refers to a polypeptide comprising an amino acid sequence that has at least about 70% sequence identity to a reference sequence, i.e., to a wild type actinohivin ([0046]). The specification further discloses that “subject” includes any human or nonhuman animal, including all vertebrates ([0036]). The specification discloses that “treating” encompasses preventing ([00139]), and that “subject in need thereof” refers to a mammalian subject diagnosed with or suspected of having a disease whom will be or has been administered a polypeptide according to a method of the invention. The “subject in need thereof” includes those subjects already with the undesired physiological change or disease as well as those subjects prone to have the physiological change or disease ([00123]). The specification discloses that in particular embodiments, the therapeutically effective amount is sufficient to significantly decrease tumor burden, improve survival or the likelihood of survival, or all three ([00145]). Instant claims 12-16 which recite a method of killing an ovarian cancer cell comprising contacting the ovarian cancer cell with a polypeptide comprising an actinohivin or a variant thereof are being interpreted as encompassing contacting that is either in vitro or in vivo (by administration to a subject). Instant dependent claim recites the limitation “optionally” with reference to the polypeptide comprising an amino acid set forth in SEQ ID NO: 16; therefore, this said claim is being interpreted as encompassing administering either a generic polypeptide comprising an actinohivin or a variant thereof or administering a polypeptide that comprises SEQ ID NO: 16 (which is SEQ ID NO: 9 with a fused IgG1 Fc region).
7. 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.
8. Claims 1-16 and 18-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Applicant has broadly claimed:
a) a method of treating ovarian cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polypeptide comprising “an” actinohivin or a” variant thereof” (claims 1-11 and 18-20); and
b) a method of killing an ovarian cancer cell, the method comprises contacting the ovaria cancer cell with a polypeptide comprising “an” actinohivin or a “variant thereof” (claims 12-16); and including the limitations of the dependent claims.
As such the claimed method administers and/or contacts “an” actinohivin or a “variant thereof” ingredient, wherein the designation “an” actinohivin indicates a broader genus than wild-type actinohivin from a particular species of Actinomycetes that is represented by SEQ ID NO: 1, and wherein the “variant thereof” may be a variant of any actinohivin, including a variant SEQ ID NO: 1, i.e., according to the definition in the specification, one having at least 70% sequence identity thereto and having the functional properties of binding a sugar and possessing HIV-virus-inhibiting activity, as is enunciated below in detail.
As is stated above in this office action in the claim interpretation section, the specification discloses that “a” wild-type actinohivin is represented by SEQ ID NO: 1, and “an” actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, and was originally identified and isolated from the actinomycetes K97-0003 strain (citing IDS reference Chiba et al.)([0044] and [00198]). The specification discloses that “as used herein, the term “variant” refers to a polypeptide comprising an amino acid sequence that has at least about 70% sequence identity to a reference sequence, i.e., a wild type actinohivin ([0046]). Thus, both “an” actinohivin and a “variant thereof” must possess the functional properties of being a sugar-binding protein that also has the functional property of anti-HIV virus activity.
The specification does not disclose a representative number of species of such actinohivin and variant thereof used in the claimed method of treatment, nor sufficient relevant identifying characteristics in the form of structure or functional characteristics coupled with a known or disclosed correlation between structure and function.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). 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"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.' " Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2163 I.A.
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." See MPEP 2163 II.3.
The specification discloses that actinohivin variants are SEQ ID NO: 2-13, and SEQ ID NO: 16 is a fusion of SEQ ID NO: 9 variant [of SEQ ID NO: 1] and an IgFc sequence and is termed “”AvFc” or “Avarin Fc” ([00171]-[00172], [00177], [00213], [00293]).
Evidentiary reference Hamorsky et al. (Mol. Ther. 2019, 27(11): 2038-2052, IDS reference) teaches that actinohivin (AH) is highly hydrophobic, prone to aggregate and is recalcitrant to efficient recombinant production. Hamorsky et al. teach that a soluble variant termed “Avaren” (an actinohivin variant) was obtained by structure-guided mutations of actinohivin [that is identical to instantly recited SEQ ID NO: 1] and subsequently fused to an IgFc region of human IgG1 subclass to create a “lectinbody” (paragraph spanning pages 2038-2039). Hamorsky et al. teach that this polypeptide possessed several advantages over the wildtype lectin, including higher HMG-binding avidity via dimerization, prolonged in vivo half-life and Fc-mediated antiviral/anti-tumor functions such as ADCC (paragraph spanning columns 1-2 on page 2039, Fig. 1 A at variant 8 (Avaren)). Hamorsky et al. teach that the overall structure in the variant appeared to be similar to that of actinohivin, although there appeared to be an increase in random coils in Avaren’s structure (page 2039 at the last full paragraph at column 1). See entire reference.
Thus Hamorsky et al. evidence that experimentation must be employed to make a variant of SEQ ID NO: 1 that has anti-HIV activity and bind to the relevant sugar(s), i.e., one of the requisite functional properties [of lectin activity or sugar binding]. Except for the fully defined variants disclosed in the instant specification, the specification nor the art, provide a structure/function relationship for variants of SEQ ID NO: 1, and also for other “actinohivins” that are not SEQ ID NO: 1. The breadth of the limitation “variant” indicates that the 114 amino acid residue SEQ ID NO: 1 native actinohiven from a particular strain of Actinomycetes may be 70% or more identical thereto, i.e, 34 residues may be different and changes may be present anywhere within the sequence. Nor do the specification and the art provide a representative number of species of such actinohivins and their variants, that bind a sugar and in addition also possess the second requisite functional property of HIV-virus-inhibiting activity.
In addition, with regard to the recitation of “wherein the polypeptide is modified” in instant dependent claim 20, the specification does not disclose a limiting definition for “modified”, but does disclose some examples at [0032]. Thus, it is clear that the term “modified” is much broader than the examples in the specification.
Therefore, it appears that the instant specification does not adequately disclose the breadth of “an” actinohivin or a “variant thereof” ingredient recited in method of the instant claims. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all such said ingredients and hence was not in possession of the method that uses them at the time the instant application was filed.
9. Claims 1-14, 16, 17, 19 and 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not disclose how to use the instant invention:
a) a method of treating ovarian cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polypeptide comprising “an” actinohivin or a” variant thereof”; and
b) a method of killing an ovarian cancer cell, the method comprises contacting the ovaria cancer cell with a polypeptide comprising “an” actinohivin or a “variant thereof”; and including the limitations of the dependent claims,
wherein the actiohivin or variant thereof does not comprise an IgFc region that has ADCC activity or an effector drug or label that can kill cancer cells.
The specification has not enabled the breadth of the claimed invention because the claims encompass an actinohivin or variant thereof polypeptide that can bind to an ovarian cancer cell but does not have anti-tumor activity in the absence of the presence of an IgFc region that has ADCC activity or effector drug or label.
The state of the art is such that it is unpredictable in the absence of appropriate evidence whether the method can be practiced in the absence of such said heterologous moieties.
As is stated above in this office action in the claim interpretation section, the specification discloses that “a” wild-type actinohivin is represented by SEQ ID NO: 1, and “an” actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, and was originally identified and isolated from the actinomycetes K97-0003 strain (citing IDS reference Chiba et al.)([0044] and [00198]). The specification discloses that “as used herein, the term “variant” refers to a polypeptide comprising an amino acid sequence that has at least about 70% sequence identity to a reference sequence, i.e., a wild type actinohivin ([0046]).
The specification discloses that actinohivin variants (of SEQ ID NO: 1) are SEQ ID NO: 2-13, with SEQ ID NO: 16 being a fusion of the SEQ ID NO: 9 variant and an IgFc sequence that is termed “”AvFc” or “Avarin Fc” ([00171]-[00172], [00177], [00213], [00293]). The specification further discloses that AvFc binds to human OVCA (ovarian cancer) cell lines in vitro and also to malignant tissue but not to normal adjacent tissue, and shows ADCC activity against the said OVACA cell lines ([0020]. The specification discloses that a murine ID8 OVCA challenge model was used to test AvFc, wherein female mice were intraperitoneally challenged with ID8 cells, and starting from 7 days post tumor challenge, mice were treated i.p. every 3 days for 28 days with either AvFc or vehicle control, with the result that survival curves were determined to be significantly increased in test animals ([0023].
The specification does not disclose working examples with regards to administration of actinohivin or one of its variants by themselves without a cancer-killing heterologous fusion element.
Evidentiary reference Hamorsky et al. (Mol. Ther. 2019, 27(11): 2038-2052, IDS reference) teaches that actinohivin (AH) is highly hydrophobic, prone to aggregate, and shtus, recalcitrant to efficient recombinant production. Hamorsky et al. teach that a soluble variant termed “Avaren” (an actinohivin variant of instantly recited SEQ ID NO: 1) was obtained by structure-guided mutations of actinohivin and subsequently fused to an IgFc region of human IgG1 subclass to create a “lectinbody” (paragraph spanning pages 2038-2039), and possessed several advantages over the wildtype lectin, including higher HMG-binding avidity via dimerization, prolonged in vivo half-life and Fc-mediated antiviral/anti-tumor functions such as ADCC (paragraph spanning columns 1-2 on page 2039, Fig. 1 A at variant 8 (Avaren)). Hamorsky et al. teach that the overall structure in the variant appeared to be similar to that of actinohivin, although there appeared to be an increase in random coils in Avaren’s structure (page 2039 at the last full paragraph at column 1). See entire reference.
There is insufficient guidance in the specification as to how to use the instant invention. Undue experimentation would be required of one skilled in the art to practice the instant invention. See In re Wands 8 USPQ2d 1400 (CAFC 1988).
10. 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.
11. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
12. Claims 1, 6-9, 12 and 15-20 are rejected under 35 U.S.C. 102(a)(i) as being anticipated by WO 2018148541 A1 (pub date 8/16/18, IDS reference).
Instant independent claim 1 recites “A method of treating ovarian cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polypeptide comprising an actinohivin or a variant thereof. Independent claim 12 recites “A method of killing an ovarian cancer cell, the method comprises contacting the ovarian cancer cell with a polypeptide comprising an actinohivin or a variant thereof.”
WO 2018148541 A1 teaches that AvFc (i.e., SEQ ID NO: 16 of the art reference that is identical to instantly recited SEQ ID NO: 16 and is an actinohivin variant comprising a sequence identical to instantly recited SEQ ID NO:9 fused to a human IgG1 Fc) or other actinohivin variant polypeptides, including SEQ ID NO: 2-15 that are identical to their instantly recited counterpart sequences or Fc fusions thereof, may be used to treat ovarian cancer in a subject, including a human, and administered in a therapeutically effective amount, including by an i.v. route (e.g., abstract, [0029]-[0044], [0063], [0064], [0093],[0095], [0096], [0098], [00136],[00137]). WO 2018148541 A1 teaches that AvFc and actinohivin (AH) both exhibited high specificity to oligomannose glycans containing terminal alpha-1, 2-linked mannose (i.e., a sugar) (e.g., [00137]) and have affinity to HIV gp120 proteins (e.g., [00138]). WO 2018148541 A1 teaches that AvFc can elicit Fc-mediated antiviral activity in addition to virion neutralization (e.g., [00138]). (As enunciated above in the claim interpretation section of this office action, the instant specification discloses that an actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, e.g., at [0044] and [00198])). WO 2018148541 A1 teaches that the terms treatment or treating include, but are not limited to, prophylaxis, reducing the likelihood of occurrence of a condition or development thereof, inhibiting the progression of a condition, arresting development of a condition, reducing severity of a condition, ameliorating or relieving symptoms associated with a condition, and causing a regression of the condition or one or more of the symptoms thereof ([0090]). WO 2018148541 A1 teaches that a therapeutically effective amount refers to the amount of a composition comprising an actinohivin variant polypeptide sufficient to produce a measurable biological response ([0096]). WO 2018148541 A1 teaches that anti-cancer activity includes reduction in tumor burden (e.g., [000141], Fig. 14A,B). WO 2018148541 A1 teaches that the actinohivin variant polypeptide in some embodiments is fused or linked to an antibody fragment that may be a Fab ([0063]). WO 2018148541 A1 teaches that other drugs may be included in the composition with the polypeptide (i.e., a second therapeutic agent, e.g., [0096]). See entire reference.
Claims 12, 15 and 16 are also included in this rejection because the method of killing an ovarian cancer cell comprising contacting the ovarian cancer cell with a polypeptide comprising an actinohivin or a variant thereof encompasses contacting that is either of in vitro or in vivo contacting (by administration to a subject), as is enunciated in the claim interpretation section of this office action above.
13. 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.
14. Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018148541 A1 (IDS reference) in view of US 2015/0125517 A1 (IDS reference).
WO 2018148541 A1 teaches that AvFc (i.e., SEQ ID NO: 16 of the art reference that is identical to instantly recited SEQ ID NO: 16 and is an actinohivin variant comprising a sequence identical to instantly recited SEQ ID NO:9 fused to a human IgG1 Fc) or other actinohivin variant polypeptides, including SEQ ID NO: 2-15 that are identical to their instantly recited counterpart sequences or Fc fusions thereof, may be used to treat ovarian cancer in a subject, including a human, and administered in a therapeutically effective amount, including by an i.v. route (e.g., abstract, [0029]-[0044], [0063], [0064], [0093],[0095], [0096], [0098], [00136],[00137]). WO 2018148541 A1 teaches that AvFc and actinohivin (AH) both exhibited high specificity to oligomannose glycans containing terminal alpha-1, 2-linked mannose (i.e., a sugar) (e.g., [00137]) and have affinity to HIV gp120 proteins (e.g., [00138]). WO 2018148541 A1 teaches that AvFc can elicit Fc-mediated antiviral activity in addition to virion neutralization (e.g., [00138]). (As enunciated above in the claim interpretation section of this office action, the instant specification discloses that an actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, e.g., at [0044] and [00198])). WO 2018148541 A1 teaches that the terms treatment or treating include, but are not limited to, prophylaxis, reducing the likelihood of occurrence of a condition or development thereof, inhibiting the progression of a condition, arresting development of a condition, reducing severity of a condition, ameliorating or relieving symptoms associated with a condition, and causing a regression of the condition or one or more of the symptoms thereof ([0090]). WO 2018148541 A1 teaches that a therapeutically effective amount refers to the amount of a composition comprising an actinohivin variant polypeptide sufficient to produce a measurable biological response ([0096]). WO 2018148541 A1 teaches that anti-cancer activity includes reduction in tumor burden (e.g., [000141], Fig. 14A,B). WO 2018148541 A1 teaches that the actinohivin variant polypeptide in some embodiments is fused or linked to an antibody fragment that may be a Fab ([0063]). WO 2018148541 A1 teaches that other drugs may be included in the composition with the polypeptide (i.e., a second therapeutic agent, e.g., [0096]). See entire reference.
WO 2018148541 A1 does not teach wherein the ovarian cancer is epithelial ovarian cancer (claims 2 and 13), nor wherein the subject has undergone primary therapy and has achieved no residual disease status (claim 3), nor wherein the subject has relapsed (recurrent) or has refractory ovarian cancer (claim 4), nor wherein the cancer is chemo-resistant (claims 5 and 14).
US 2015/0125517 A1 discloses a method to treat ovarian cancer wherein the ovarian cancer is epithelial ovarian cancer ([0011]). US 2015/0125517 A1 further discloses treating ovarian cancer wherein the subject has undergone primary therapy and has achieved no residual disease status and to prevent recurrence to extend progression free survival ([0051]). US 2015/0125517 A1 discloses wherein the subject has relapsed or has refractory ovarian cancer such as platinum-refractory or platinum-resistant ovarian cancer ([0028], [0004]).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as per the teaching of the primary art reference, including wherein as disclosed by the secondary art reference, the ovarian cancer is epithelial ovarian cancer, wherein the patient has undergone primary therapy and has achieved no residual disease status, wherein the subject has relapsed or has refractory ovarian cancer, including platinum-refractory ovarian cancer.
One of ordinary skill in the art would have been motivated to do this in order to treat patients who have particular subtypes of ovarian cancer, to prevent recurrence to extend progression free survival, and to treat patients who have relapsed, have refractory ovarian cancer, or chemo-resistant cancer.
Claims 12-16 are also included in this rejection because the method of killing an ovarian cancer cell comprising contacting the ovarian cancer cell with a polypeptide comprising an actinohivin or a variant thereof encompasses contacting that is either of in vitro or in vivo contacting (by administration to a subject). Claims 11 and 12 are included in this rejection because it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as either an outpatient or an inpatient in order to accommodate the state of the patient.
15. Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018148541 A1 (IDS reference) in view of US 2015/0125517 A1 (IDS reference) and Chen et al. (Tumor Biol. 7/2017, pages 1-12).
WO 2018148541 A1 teaches that AvFc (i.e., SEQ ID NO: 16 of the art reference that is identical to instantly recited SEQ ID NO: 16 and is an actinohivin variant comprising a sequence identical to instantly recited SEQ ID NO:9 fused to a human IgG1 Fc) or other actinohivin variant polypeptides, including SEQ ID NO: 2-15 that are identical to their instantly recited counterpart sequences or Fc fusions thereof, may be used to treat ovarian cancer in a subject, including a human, and administered in a therapeutically effective amount, including by an i.v. route (e.g., abstract, [0029]-[0044], [0063], [0064], [0093],[0095], [0096], [0098], [00136],[00137]). WO 2018148541 A1 teaches that AvFc and actinohivin (AH) both exhibited high specificity to oligomannose glycans containing terminal alpha-1, 2-linked mannose (i.e., a sugar) (e.g., [00137]) and have affinity to HIV gp120 proteins (e.g., [00138]). WO 2018148541 A1 teaches that AvFc can elicit Fc-mediated antiviral activity in addition to virion neutralization (e.g., [00138]). (As enunciated above in the claim interpretation section of this office action, the instant specification discloses that an actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, e.g., at [0044] and [00198])). WO 2018148541 A1 teaches that the terms treatment or treating include, but are not limited to, prophylaxis, reducing the likelihood of occurrence of a condition or development thereof, inhibiting the progression of a condition, arresting development of a condition, reducing severity of a condition, ameliorating or relieving symptoms associated with a condition, and causing a regression of the condition or one or more of the symptoms thereof ([0090]). WO 2018148541 A1 teaches that a therapeutically effective amount refers to the amount of a composition comprising an actinohivin variant polypeptide sufficient to produce a measurable biological response ([0096]). WO 2018148541 A1 teaches that anti-cancer activity includes reduction in tumor burden (e.g., [000141], Fig. 14A,B). WO 2018148541 A1 teaches that the actinohivin variant polypeptide in some embodiments is fused or linked to an antibody fragment that may be a Fab ([0063]). WO 2018148541 A1 teaches that other drugs may be included in the composition with the polypeptide (i.e., a second therapeutic agent, e.g., [0096]). See entire reference.
WO 2018148541 A1 does not teach wherein the ovarian cancer is epithelial ovarian cancer (claims 2 and 13), nor wherein the subject has undergone primary therapy and has achieved no residual disease status (claim 3), nor wherein the subject has relapsed (recurrent) or has refractory ovarian cancer (claim 4), nor wherein the cancer is chemo-resistant (claims 5 and 14).
US 2015/0125517 A1 discloses a method to treat ovarian cancer wherein the ovarian cancer is epithelial ovarian cancer ([0011]). US 2015/0125517 A1 further discloses treating ovarian cancer wherein the subject has undergone primary therapy and has achieved no residual disease status and to prevent recurrence to extend progression free survival ([0051]). US 2015/0125517 A1 discloses wherein the subject has relapsed or has refractory ovarian cancer such as platinum-refractory or platinum-resistant ovarian cancer ([0028], [0004]).
Chen et al. teach that N-mannnose glycans (i.e., oligomannan glycans such as taught by the primary art reference to be bound by actinohivin) are present on epithelial ovarian cancer cells (see entire reference, especially abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as per the teaching of the primary art reference, including wherein as disclosed by the secondary art references, the ovarian cancer is epithelial ovarian cancer, wherein the patient has undergone primary therapy and has achieved no residual disease status, wherein the subject has relapsed or has refractory ovarian cancer, including platinum-refractory ovarian cancer.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so in order to treat patients who have particular subtypes of ovarian cancer, to prevent recurrence to extend progression free survival, and to treat patients who have relapsed, have refractory ovarian cancer, or chemo-resistant cancer.
Claims 12-16 are also included in this rejection because the method of killing an ovarian cancer cell comprising contacting the ovarian cancer cell with a polypeptide comprising an actinohivin or a variant thereof encompasses contacting that is either of in vitro or in vivo contacting (by administration to a subject). Claims 11 and 12 are included in this rejection because it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as either an outpatient or an inpatient in order to accommodate the state of the patient.
16. 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.
17. Claims 1, 6-9, 12 and 15-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 10, 12 and 17 of copending Application No. 18/261,950 in view of WO 2018148541 A1 (IDS reference).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 9, 13 and 17 of 18/261,950 are drawn to a method of treating a cancer in a subject in need thereof, comprising administering or providing for administration a therapeutically effective amount of a polypeptide that specifically binds the high-mannose-type glycan epitope to the subject if abnormal accumulation in a biological sample from the subject is determined to be present.
Claim 10 and 12 of 18/261,950 are drawn to a method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide that specifically binds a high-mannose-type glycan epitope, wherein the cancer is characterized by an abnormal cell-surface accumulation of high-mannose glycans.
The claims of 12/261,950 do not recite the identity of the said polypeptide.
WO 2018148541 A1 teaches polypeptides that can bind to oligomannose glycans on ovarian cancer cells to reduce the tumor burden as follows.
WO 2018148541 A1 teaches that AvFc (i.e., SEQ ID NO: 16 of the art reference that is identical to instantly recited SEQ ID NO: 16 and is an actinohivin variant comprising a sequence identical to instantly recited SEQ ID NO:9 fused to a human IgG1 Fc) or other actinohivin variant polypeptides, including SEQ ID NO: 2-15 that are identical to their instantly recited counterpart sequences or Fc fusions thereof, may be used to treat ovarian cancer in a subject, including a human, and administered in a therapeutically effective amount, including by an i.v. route (e.g., abstract, [0029]-[0044], [0063], [0064], [0093],[0095], [0096], [0098], [00136],[00137]). WO 2018148541 A1 teaches that AvFc and actinohivin (AH) both exhibited high specificity to oligomannose glycans containing terminal alpha-1, 2-linked mannose (i.e., a sugar) (e.g., [00137]) and have affinity to HIV gp120 proteins (e.g., [00138]). WO 2018148541 A1 teaches that AvFc can elicit Fc-mediated antiviral activity in addition to virion neutralization (e.g., [00138]). (As enunciated above in the claim interpretation section of this office action, the instant specification discloses that an actinohivin is a sugar-binding protein exhibiting anti-HIV virus activity, e.g., at [0044] and [00198])). WO 2018148541 A1 teaches that the terms treatment or treating include, but are not limited to, prophylaxis, reducing the likelihood of occurrence of a condition or development thereof, inhibiting the progression of a condition, arresting development of a condition, reducing severity of a condition, ameliorating or relieving symptoms associated with a condition, and causing a regression of the condition or one or more of the symptoms thereof ([0090]). WO 2018148541 A1 teaches that a therapeutically effective amount refers to the amount of a composition comprising an actinohivin variant polypeptide sufficient to produce a measurable biological response ([0096]). WO 2018148541 A1 teaches that anti-cancer activity includes reduction in tumor burden (e.g., [000141], Fig. 14A,B). WO 2018148541 A1 teaches that the actinohivin variant polypeptide in some embodiments is fused or linked to an antibody fragment that may be a Fab ([0063]). WO 2018148541 A1 teaches that other drugs may be included in the composition with the polypeptide (i.e., a second therapeutic agent, e.g., [0096]). See entire reference.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used the polypeptide(s) that can bind to oligomannose glycans on ovarian cancer cells taught by WO 201848541 A1 in the methods recited in the claims of 18/261,950 that administer a polypeptide that binds to a high-mannose-type glycan, including performing a prior step of determining if a sample from the subject to be treated expresses the oligomannan glycan(s).
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to reduce the tumor burden in the subject as is taught by WO 201848541 A1.
18. Claims 2-5 and 10-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 10, 12 and 17 of copending Application No. 18/261,950 as applied to instant claims 1, 6-9, 12 and 15-20 in view of WO 2018148541 A1 (IDS reference), and further in view of US 2015/0125517 A1 (IDS reference) and Chen et al. (Tumor Biol. 7/2017, pages 1-12).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The method recited in the claims of 18/261,950 has been enunciated above and will not be repeated herein, nor will the teachings of WO 201848541 A1.
The claims of 18/261,950 do not recite wherein, nor does WO 2018148541 A1 teach that ovarian cancer is epithelial ovarian cancer (as is recited in instant claims 2 and 13), nor that the subject has undergone primary therapy and has achieved no residual disease status (as is recited in instant claim 3), nor that the subject has relapsed (recurrent) or has refractory ovarian cancer (as is recited in instant claim 4), nor wherein the cancer is chemo-resistant (as is recited in instant claims 5 and 14), nor that the polypeptide is administered in an inpatient or outpatient clinical setting (as is recited in instant claims 11 and 10, respectively).
US 2015/0125517 A1 discloses a method to treat ovarian cancer wherein the ovarian cancer is epithelial ovarian cancer ([0011]). US 2015/0125517 A1 further discloses treating ovarian cancer wherein the subject has undergone primary therapy and has achieved no residual disease status and to prevent recurrence to extend progression free survival ([0051]). US 2015/0125517 A1 discloses wherein the subject has relapsed or has refractory ovarian cancer such as platinum-refractory or platinum-resistant ovarian cancer ([0028], [0004]).
Chen et al. teach that N-mannnose glycans (i.e., oligomannan glycans such as taught by the primary art reference to be bound by actinohivin) are present on epithelial ovarian cancer cells (see entire reference, especially abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as per the teaching of the WO 2018148541 A1 art reference as is stated in the prior rejection as the subject in the method recited in the claims of 18/261,950, but including wherein as disclosed by the US 2015/0125517 A1 art reference, the ovarian cancer is epithelial ovarian cancer as is disclosed by Chen et al. to express the oligomannan glycans to which the polypeptides taught by the WO 2018148541 A1 art reference bind, wherein the patient has undergone primary therapy and has achieved no residual disease status, wherein the subject has relapsed or has refractory ovarian cancer, including platinum-refractory ovarian cancer, all of which are disclosed by the US 2015/0125517 A1 art reference.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to treat patients who have particular subtypes of ovarian cancer such as epithelial ovarian cancer, to prevent recurrence to extend progression free survival, and to treat patients who have relapsed, have refractory ovarian cancer, or chemo-resistant cancer.
Claims 11 and 12 are included in this rejection because it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have treated an ovarian cancer patient as either an outpatient or an inpatient in order to accommodate the state of the patient.
19. No claim is allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, MISOOK YU can be reached on 571-272-0839. 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). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641