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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/05/24 has been entered.
Claims 1-2, 6-8, and 11 have been amended. Claims 9-10 have been canceled. Claims 12-14 have been added. Claims 1-8 and 11-14 are pending and under examination.
Withdrawn Rejections
The rejection of claim 7 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s amendment thereto. See paragraph 14, page 11 of the previous Office action.
The rejection of claim 7 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the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends, is withdrawn in light of Applicant’s amendment thereto. See paragraph 16, page 11 of the previous Office action.
Maintained Rejections
Claim Rejections - 35 USC § 102
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.
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.
Claim(s) 1-6 and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grabosch et al. ((June 2017). Novel combination immunotherapy with MUC1 vaccination and immune checkpoint blockade in ovarian cancer. Gynecologic Oncology, 145, 86).
The claims are drawn to a composition for treating cancer comprising: an effective amount of rintatolimod and an effective amount of an anti-PD-L1 antibody; wherein the cancer is selected from the group consisting of: pancreatic cancer, renal cell carcinoma, colorectal cancer, and melanoma; wherein, when the effective amount of rintatolimod and the effective amount of an anti- PD-L1 antibody are combined, the combination is effective for treating the cancer.
Grabosch et al. teach a composition comprising Ampligen (also known as rintatolimod) and anti-PD-L1 antibodies (See abstract). Grabosch et al. teach that the composition is for treating ovarian cancer (See abstract). Grabosch et al. teach that that the combination treatment resulted in significant survival over control treated mice (See abstract). Regarding the limitations wherein the composition improves progression free survival or life expectancy of a patient administered the composition, wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of proliferation or tumor cells, wherein the synergistic effect is selected from the group consisting of: inhibiting tumor growth; inducing tumor cell death; increasing tumor regression; preventing tumor recurrence; preventing tumor growth; preventing tumor spread; delaying tumor recurrence; delaying tumor growth; delaying tumor spread; and promoting tumor elimination, and wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of the proliferation of tumor cells greater than (1) a composition comprising ATIE alone, (2) a composition comprising checkpoint inhibitor alone, or (3) a sum of (1) and (2), the prior art composition comprises the same components as the claimed composition. Therefore, the composition taught by the prior art would inherently have the same properties as the claimed composition. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Thus, Grabosch et al. anticipate the claims.
Applicant’s Arguments
Applicant argues that treatment of pancreatic cancer, renal cell carcinoma, colorectal cancer, or melanoma is neither disclosed nor suggested by Grabosch.
Applicant argues that while the amounts of MUC1 peptide with Ampligen and the anti-PD-L1 antibody are not disclosed, Grabosch clearly does not teach or suggest the combined amounts of Ampligen and the anti-PD-L1 antibody would effectively treat even ovarian cancer. Applicant argues that in particular, since treatment by each as a single agent was not effective for the amounts used and addition of MUC 1 peptide may be required for effective treatment, there is no evidence that even suggests the combination of effective amounts of rintatolimod and an anti- PD-L1 antibody would be effective for treating cancer.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive.
In response to Applicant’s arguments that Grabosch does not teach treatment of pancreatic cancer, renal cell carcinoma, colorectal cancer, or melanoma, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the prior art teaches a composition comprising an effective amount of rintatolimod and an effective amount of anti-PD-L1 antibody. The prior art composition is capable of performing the intended use, and thus, meets the limitations of the claims.
In response to Applicant’s argument that the composition of may require the addition of MUC 1 peptide, it should be noted that the instant claims recite the transitional term “comprising”. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Thus, additional elements, such as the MUC1 peptide, may be included to the composition and still form a construct within the scope of the claim.
Claim Rejections - 35 USC § 103
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 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.
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.
Claim(s) 1-8 and 11-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carter et al. (WO2010047835 A2, published April 29, 2010) in view of Steele et al. (US Patent Application Publication 2016/0031990, published February 4, 2016).
The claims are drawn to a composition for treating cancer comprising: an effective amount of rintatolimod and an effective amount of an anti-PD-L1 antibody; wherein the cancer is selected from the group consisting of: pancreatic cancer, renal cell carcinoma, colorectal cancer, and melanoma; wherein, when the effective amount of rintatolimod and the effective amount of an anti- PD-L1 antibody are combined, the combination is effective for treating the cancer.
Carter et al. teach a composition comprising rugged dsRNA having the ribo(In) • ribo(C12U)n, which is the formula for rintatolimod (See pages 4-6 and 9). Carter et al. teach that the composition comprises a pharmaceutically acceptable carrier (See pages 6 and 9-12). Carter et al. teach that the composition is useful for treating a disease or pathological condition that is characterized by abnormal cell proliferation (e.g., neoplasm or tumor, other transformed cells). A pharmaceutical composition which is comprised of rugged dsRNA in an amount sufficient to bind to TLR3 is administered to the subject. Carter et al. teach that the cancer is nasopharyngeal cancer, Hodgkin's lymphoma, Burkitt's lymphoma, and other B lymphomas; human hepatitis B and C viruses (HBV and HCV) are associated with liver cancer; human herpesvirus 8 (HHV8) is associated with Kaposi's sarcoma; human papillomaviruses (e.g., HPV6, HPV11 , HPV16, HPV18, or combination thereof) are associated with cervical cancer, anal cancer, and genital warts; and human T-lymphotrophic virus (HTLV) is associated with T-cell leukemia and lymphoma. Cancers include those originating from the gastrointestinal (e.g., esophagus, colon, intestine, ileum, ' rectum, anus, liver, pancreas, stomach), genitourinary (e.g., bladder, kidney, prostate), musculoskeletal, nervous, pulmonary (e.g., lung), or reproductive (e.g., cervix, ovary, testicle) organ systems (See pages 9-10).
Carter et al. do not teach that the composition comprises an anti-PD-L1 antibody.
Steele et al. teach a pharmaceutical composition comprising an anti-PD-L1 antibody (See paragraphs 0012-0016 and 0051). Steele et al. teach that the anti-PD-L1 antibody is MEDI-4736 (See paragraph 0069). Steele et al. teach that the composition is useful for treating cancer, such as head and neck cancer, lung cancer, NSCLC, oropharyngeal squamous cell carcinoma, breast cancer, and melanoma (See paragraphs 0012, 0115, and 0142).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition Carter et al. to include the checkpoint inhibitor anti-PD-L1 because Steele et al. teach that anti-PD-L1 is also useful for treating cancer. One of ordinary skill in the art would be motivated to make a composition comprising rugged dsRNA having the formula ribo(In) • ribo(C4-29U)n, ribo(In) • ribo(C11-14U)n, or ribo(In) • ribo(C12U)n, and a checkpoint inhibitor because it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Regarding the limitations wherein the composition improves progression free survival or life expectancy of a patient administered the composition, wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of proliferation or tumor cells, wherein the synergistic effect is selected from the group consisting of: inhibiting tumor growth; inducing tumor cell death; increasing tumor regression; preventing tumor recurrence; preventing tumor growth; preventing tumor spread; delaying tumor recurrence; delaying tumor growth; delaying tumor spread; and promoting tumor elimination, and wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of the proliferation of tumor cells greater than (1) a composition comprising ATIE alone, (2) a composition comprising checkpoint inhibitor alone, or (3) a sum of (1) and (2), the composition taught by the combination of references comprises the same components as the claimed composition. Therefore, the composition taught by the combination of references would necessarily have the same properties as the claimed composition. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Applicant’s Arguments
Applicant argues that neither reference has described a utility of a combination of a double stranded RNA (e.g., rintatolimod) and an anti-PD-L1 antibody. Applicant argues that one of ordinary skill in the art would not assume that any two anti-cancer drugs to be obvious at least because of the following: (1) A drug combination may have a combination toxicity or even synergistic toxicity that exceeds the benefit of any therapeutic anti-cancer effect; (2) A drug combination may not have an additive anti-cancer activity because, for example, the two drugs may work in the same pathway; (3) A drug combination may only have an additive therapeutic effect but a synergistic toxicity effect; (4) A drug combination may inactivate each other's therapeutic effect. For example, one drug may degrade a second drug, or one drug may work in a mechanistic pathway that is antagonistic to a second drug's mechanistic pathway.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive. In response to Applicant’s argument that neither reference has described a utility of a combination of a double stranded RNA (e.g., rintatolimod) and an anti-PD-L1 antibody, the references were not used in an anticipation rejection, but rather, an obviousness rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding the combination of references, Carter et al. teach a composition comprising rintatolimod for treating cancer and Steele et al. teach a composition comprising an anti-PD-L1 antibody for treating cancer. Thus, as set forth in the previous office action, since Carter et al. and Steele et al. teach a composition comprising a combination therapy for the treatment of cancer, and the instant claims comprise a combination of agents known in the art to be useful for the same purpose, the claims are subject to an In re Kerkhoven analysis (In re Kerkhoven, 626, F.2s 846,850, 205 USPQ 1069, 1072 (CCPA 1980)). The court held that it is obvious to combine two compositions, in order to form a third composition, when each of the two compositions is taught by the prior art to be useful for the same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06).
In response to Applicant’s argument one of ordinary skill in the art would not assume that any two anti-cancer drugs could be combined for therapy, the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-8 and 11-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-9, 12-13, 17-24, and 26-52 of copending Application No. 17/416,358 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass a composition comprising an anti-PD-L1 checkpoint inhibitor and rintatolimod (rIn•r(C12U)n). The ‘358 claims teach wherein the composition comprises a pharmaceutically acceptable carrier. The ‘358 claims teach the same composition as the claimed composition, and therefore, the ‘358 composition would possess the same properties of improving progression free survival or life expectancy of a patient administered the composition. The ‘358 claims teach wherein the combination of the tdsRNA and the checkpoint inhibitor provide a synergistic effect in the treatment of cancer or in the proliferation of tumor cells. The ‘358 claims teach wherein the synergistic effect is selected from the group consisting of: increasing survival of the subject; increasing time of progression of the subject; inhibiting tumor growth; inducing tumor cell death; increasing tumor regression; preventing tumor recurrence; preventing tumor growth; preventing tumor spread; delaying tumor recurrence; delaying tumor growth; delaying tumor spread; and promoting tumor elimination. The ‘358 claims teach wherein the tdsRNA and the checkpoint inhibitor together provides a synergistic effect in the treatment of cancer or in an inhibition of the proliferation of tumor cells over tdsRNA alone, checkpoint inhibitor alone, or a sum of tdsRNA alone and checkpoint inhibitor alone. The ‘358 claims teach wherein AITE is rIn•r(C11-14U)n. The ‘358 claims teach wherein the checkpoint inhibitor is selected from the group consisting of an antibody, a monoclonal antibody, a humanized antibody, a fully human antibody, a fusion protein, a PEGylated antibody, a multimeric antibody, an antibody fragment comprising an epitope binding region, and a combination thereof. The ‘358 claims teach wherein the checkpoint inhibitor is selected from the group consisting of: ipilimumab (YERVOY®, (Bristol-Myers Squibb); nivolumab (OPDIVO®, Bristol-Myers Squibb); pembrolizumab (KEYTRUDA®; Merck); and a combination thereof. It should be noted that ipilimumab is an antibody that binds to CTLA-4, nivolumab is an antibody that binds to PD-1, and pembrolizumab is an antibody that binds to PD-1. The ‘358 claims teach wherein the checkpoint inhibitor inhibits, interacts with or binds to a checkpoint protein, a ligand of a checkpoint protein, or a receptor of a checkpoint protein selected from the group consisting of: atezolizumab, avelumab, BMS-936559, and durvalumab and a combination thereof.
The difference between the instant claims and the ‘358 claims is that the instant claims are drawn to a product and the ‘358 claims are drawn to a method. However, the product of the instant claims is required to practice the method of the ‘358 claims. Thus, the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments
Applicant argues that Applicant note that the current claims and the claims of the 17/416,358 Application are both changing during prosecution and neither claim set has been allowed. The current amendment to the claims render the claim sets sufficiently different to be patentable over each other. Applicant argues that after an indication of allowance in the instant or reference application, the claims in the other may be amended to avoid any issue of double patenting.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive. The ‘358 claims recite rIn•r(C12U)n, which is the formula for rintatolimod. The ‘358 claims also recite a checkpoint inhibitor, wherein the checkpoint inhibitor is selected from the group consisting of atezolizumab, avelumab, BMS-936559, and durvalumab. Although the instant claims are drawn to a product and the ‘358 claims are drawn to a method, the product of the instant claims is required to practice the method of the ‘358 claims Thus, the claims are not patentably distinct.
Claim Status
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA CARTER whose telephone number is (571)272-2932. The examiner can normally be reached 8:00-5:00 pm.
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
