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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 8/27/2025 wherein claims 1, 3, 22, 24, and 25 were amended and claims 2, 14-16, 21, and 23 were canceled. In addition, a substitute specification was submitted on 8/27/2025.
Note(s): Claims 1, 3-13, 17-20, 22, 24, and 25 are pending.
Priority
This application is a CON of PCT/US2020/061775 filed 11/23/2020 and PCT/US2020/061775 claims benefit to PRO 62938845 filed 11/21/2019. The earliest effective filing date is 11/21/2019. The pending invention is fully supported in the provisional application.
Information Disclosure Statement
The information disclosure statement filed 8/27/2025 was considered.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 8/27/2025 to the rejection of claims 1-25 made by the Examiner under 35 USC 103, 112, and/or double patenting have been fully considered and deemed persuasive-in-part for the reasons set forth below.
Double Patenting Rejections
The outstanding double patenting rejections are WITHDRAWN because Applicant amended the claims to overcome the rejections.
112 Second Paragraph Rejections
All outstanding 112 second paragraph rejections are WITHDRAWN because Applicant amended the claims to overcome the rejections.
103 Rejection
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 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, 3-13, 17-20, 22, 24, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Andreeff et al (US 2005/0238707) in view of Winton et al (N. Engl. J. Med, 2005, Vol. 352, No. 25, pages 2589-2597).
Independent claim 1 is directed to a method of treating cancer in the lung comprising administering a therapeutically effective amount of liposomal annamycin to a subject wherein the subject has primary or metastatic cancer in the lung.
Claim 3 is directed to the primary lung cancer being a non-small cell lung carcinoma (NSCLC) or small cell lung carcinoma (SCLC). Claim 4 is directed to the primary lung cancer being adenocarcinoma, squamous cell carcinoma, or large cell carcinoma. Claim 5 is directed to metastatic cancer in the lung. Claim 6 is directed to the metastasis of a primary cancer that is selected from bladder, breast, colorectal, head and neck, kidney, melanoma, pancreatic, prostate, or ovarian cancer.
Andreeff et al is directed to a method of treating cancer in a subject using a composition comprising liposomal annamycin (see entire document, especially, abstract). The composition may be administered to subjects having lung cancer (page 5, paragraph [0061], especially, line 6).
According to Andreeff et al, annamycin is a therapeutically effective liposomal anthracycline therapy in the slowing or stasis of cancer progression. In addition, it is disclosed that in some embodiments therapeutically effective dosing with liposomal annamycin further included regression and complete remission of cancer (page 3, paragraph [0035]). Still, Andreeff et al disclose that their compositions inhibit the proliferation of neoplastic cells (page 5, paragraph [0060). The various cancers that may be treated with the liposomal composition include breast, ovary, lung, sarcomas, melanoma, prostate, and renal (kidney) (page 5, paragraph [0061]). Thus, the limitations of claims 1 and 3-6 are met.
Claim 7 is directed to metastatic sarcoma. Claim 8 is directed to metastatic cancer from an unknown primary source.
Andreeff et al disclose that the liposomal annamycin is effective is slowing or stasis of cancer progression (page 3, paragraph [0035]). Subjects having sarcomas (e.g., soft tissue, osteogenic, and Kaposi’s) were administered the liposomal annamycin (page 5, paragraph [0061], lines 7 and 9). While the document does not specifically state that the metastatic cancer is from an unknown primary source, it would have been obvious to a skilled artisan prior to the effective filing that since the population of subjects are those experiencing refractory (stubborn, unmanageable, and/or resistance) cancer as well as those undergoing relapsed (someone that suffers deterioration after a period of improvement) cancer with the focus on treating such subjects that the cancers included those of an unknown primary source. Also, subjects in precarious conditions, subjects needing dosage adjustments, and subjects with and unfavorable response were administered the liposomal annamycin composition. Thus, the focus of Andreeff et al was providing treatment to such subjects regardless of the primary source (page 3, paragraphs [0027] and [0041]; pages 4-5, paragraph [0058]; page 5, paragraph [0059]). For the reasons herein, claims 7 and 8 are obvious.
Claim 9 is directed to the liposomal annamycin composition further contain at least one chemotherapeutic agent. Claim 10 is directed to a list of chemotherapeutic agents including daunorubicin, doxorubicin, cisplatin, and carboplatin.
Andreeff et al disclose that the liposomal annamycin may be used in combination with antineoplastic drugs. Possible anti-cancer drugs include doxorubicin, daunorubicin, carboplatin, and cisplatin (page 3, paragraph [0041]; page 5, paragraph [0063]). Thus, the limitations of claims 9 and 10 are met.
Claim 11 is directed to a combination comprising at least one chemotherapeutic agent selected from (a) cyclophosphamide, doxorubicin, and vincristine; (b) mitomycin, vindesine and cisplatin; and (c) cisplatin and vinorelbine; and cisplatin, etoposide and ifosfamide. Claim 13 is directed to a method of resecting the lung cancer and/or administering radiation therapy.
While Andreeff et al disclose that the liposomal composition may contain at least one chemotherapeutic agent (e.g., cisplatin) and be used in the treatment of lung cancer (page 5, paragraphs [0061] and [0063]), the document does not disclose the specific combinations in claim 11. However, Winton et al was made of record for its disclosure that vinorelbine in combination with cisplatin are well known in the art to be used in resected non-small cell lung cancer. It is disclosed that vinorelbine in combination with cisplatin has an acceptable level of toxicity and prolongs disease free and overall survival among subjects with completely resected early stage non-small cell lung cancer. Hence, it would be obvious to use a liposomal annamycin composition comprising cisplatin and vinorelbine for treatment of lung cancer subjects. Also, one would be motivated to use the combination in subjected having resected lung cancer. Still, Winton et al disclose that radiotherapy (radiation) may be used in the treatment of the subjects (see entire document, especially, abstract; page 2589, ‘Conclusions’; page 2595, left and right columns, bridging paragraph; page 2595, Figure 1). Thus, the limitations of claim 11 and 13 are met.
Claim 12 is directed to the composition comprising at least one immunotherapeutic agent.
Andreeff et al disclose that the liposomal annamycin composition may further comprising immunotherapeutic agents such as antibiotics, and interferon, for example (page 5, paragraph [0063]). Thus, the limitation of claim 12 is met.
Claims 17 and 18 are directed to administering the composition weekly (claim 17) and every two, three, or four weeks (claim 18).
Andreeff et al disclose that subjects are evaluated over 8, 14, 21, and 28 days and liposomal annamycin is administered on a regimen as needed (page 4, paragraph [0055] through page 5, paragraph [0058]). In some instances, the regimen is repeated every 4-6 weeks). Thus, the limitations of claims 17 and 18 are met.
Claim 19 is directed to a liposomal composition comprising annamycin, one or more lipids, and one or more non-ionic surfactants. Claim 20 is directed to the composition of claim 19 further comprising dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG). Claim 22 is directed to the surfactant being polyoxyethylene sorbitan monolaurate.
Andreeff et al disclose a liposomal annamycin compositions that comprises annamycin, dimysteroyl phosphatidyl choline (DMPC), dimyristoyl phosphatidyl glycerol (DMPG), and Tween 20 (polyoxyethylene sorbitan monolaurate). Thus, the limitations of claims 19, 20, and 22 are met.
Claim 24 is directed to a preliposomal annamycin lyophilizate that comprises 1.8-2.2 wt % annamycin; 3-3.4 wt % Polysorbate 20; and 94.4-95.2 wt % DMPG and/or DMPC wherein lyophilizate is reconstituted. Claim 25 is directed to DMPC of 65.3-67.3 wt % and DMPG is 27.1-29.9 wt %.
Andreeff et al disclose a preliposomal annamycin composition comprising 50 mg annamycin, 1750 mg DMPC, 750 mg DMPG, and 85 mg Tween 20 (Polysorbate 20). Also, Andreeff et al disclose a preliposomal annamycin composition comprising 10 mg annamycin, 350 mg DMPC, 150 mg DMPG, and 17 mg Tween 20 (Polysorbate 20). Thus, after calculations one has 2 wt % annamycin, 66 wt % DMPC, 28 wt %DMPG, and 3% Tween 20.
Andreeff et al disclose that annamycin is conveniently provided in the form of a preliposomal lyophilized powder containing a mixtures of phospholipids (page 4, paragraph [0044]). The lyophilate is reconstituted on the day of use (page 4, paragraph [0047]). Thus, the limitations of claims 24 and 25 are met.
For the reasons set forth herein, the cited prior art renders obvious the pending invention.
APPLICANT’S ASSERTIONS
In summary, the following assertions are made: (1) the office action is improperly conclusory and lacks a proper Graham analysis. Applicant asserts that Andreeff et al when read in totality does not lead one of ordinary skill in the art to administer liposomal annamycin to treat primary or metastatic lung cancer with a reasonable expectation of success. (2) Andreeff et al discloses that liposomal annamycin was tested in Lewis lung carcinoma cells [0009] and that the paragraph only states that liposomal annamycin had the greatest antitumor activity against leukemia cells. It is asserted that Andreeff et al’s statement that annamycin was tested in other cancer cell lines and subsequent failure to report efficacy in those cell line amounts to a teaching away and a failure to considered the teaching of the prior art as a whole under Graham.
(3) Andreeff’s reference to lung cancer was merely an aside and one of ordinary skill in the art would not conclude that liposomal annamycin was actually useful in the treatment of lung cancer. Applicant asserts that Andreeff et al only provided evidence of treating two patients with AML (acute promyelocytic leukemia) in Examples 1 and 2. Applicant concludes that primary and metastatic cancers in the lung are significantly different from AML and a skilled artisan would not have been reasonably motivated to modify Andreeff et al to arrive at the claimed invention.
(4) It is asserted that impermissible hindsight was used in examining this application. As a result, it is asserted that Andreeff et al does not provide the missing motivation or establish a reasonable expectation of success to the presently claimed invention. In addition, it is asserted that the Examiner did not take into account the unexpected, surprising results included in the specification. Applicant’s make reference to Examples 1-4 and Figure 1-10.
EXAMINER’S RESPONSE
All of Applicant’s arguments were considered and deemed non-persuasive for reasons set forth in the office action mailed 5/30/2025 and those set forth below.
First, Applicant is respectfully reminded that the rejection is a combination rejection. As a result, it is not required that the primary reference (Andreeff et al) disclose all of the limitations of the pending claims. Secondly, the following rebuttal is made to Applicant’s assertions.
In regards to assertion (1) that the office action is improperly conclusory, lacks a proper Graham analysis, and Andreeff et al when read in totality does not lead one of ordinary skill in the art to administer liposomal annamycin to treat primary or metastatic lung cancer with a reasonable expectation of success, the response is as follows.
Andreeff et al is specifically directed to treating cancer by administering a liposomal annamycin. (1a) While the document focuses on leukemia as a preferred embodiment (see abstract and Examples 1 and 2, for example), the document reads on other cancers including lung cancer (page 1, paragraph [0008]), see excerpt below. Thus, it would have been obvious to a skilled artisan prior to Applicant’s effective filing date to recognize that not only leukemia, but lung carcinoma cells, as well as other types of cancers may be treated with annamycin. Applicant is respectfully reminded that a reference is not limited to its preferred embodiment, but must be considered for what it teaches as a whole.
Page 1, paragraph [0008]
The in vivo antitumor activity of L-Annamycin was tested in leukemia (L120),
melanoma (B16), reticulosarcoma (m5076), and Lewis lung carcinoma cells.
(1b) On page 2, paragraph [0019] (see excerpt below), Andreeff et al discloses that their method of treating a cancer subject is someone with a cancer such as leukemia and with liposomal annamycin. The skilled artisan, using any standard dictionary (e.g., Merriam-Webster’s Dictionary) would recognize that the phrase ‘such as’ is an idiom that is used to introduce and example or series of examples. ‘Such as’ terminology also appears on page 5 in paragraph [0062] as it relates to cancer. As a result, a skilled artisan would not limit the teachings of Andreeff et al to only read on leukemia.
Page 2, paragraph [0019]
This invention includes a method of treating a subject having relapsed
or refractory cancer such as leukemia with liposomal annamycin by the steps of
(1c) Andreeff et al continues to discuss liposomal annamycin and on page 5, paragraph [0061] discloses a list of cancers the invention encompasses which encompasses leukemia as well as lung cancer, see excerpt below. Thus, it would have been obvious to the skilled artisan (c1) that the teachings of Andreeff et al are not limited to leukemia and (c2) the teachings of the document also read on lung cancer.
Page 5, paragraph [0061]
Thus, these compositions can be used in cancers including blood cancers
such as leukemia with particular reference to AML. Note is made of Hodgkin’s
disease, non-Hodgkin’s lymphomas, acute and chronic lymphocytic leukemias, multiple
myeloma, neuroblastoma, breast, ovary, and lung cancer, Wilms’ tumor cervix,
testis, and soft tissue sarcomas. Further noted is chronic granulocytic leukemia,
malignant melanoma, choriocarcinoma, mycosis fungiodes, osteogenic sarcoma, hairy
cell leukemia, Kaposi’s sarcoma, essential thrombocytosis, prostate cancer and renal cancer.
In regards to assertion (2) that Andreeff et al discloses that liposomal annamycin was tested in Lewis lung carcinoma cells [0009] and that the paragraph only states that liposomal annamycin had the greatest antitumor activity against leukemia cells, the following response is given.
(2a) As detailed in the section supra, the teachings of Andreeff et al are not limited to the preferred embodiment (leukemia), but also include lung as well as other types of cancers.
In regards to Applicant’s assertion that annamycin was tested in other cancer cell lines and subsequent failure to report efficacy in those cell line amounts to a teaching away and a failure to considered the teaching of the prior art as a whole under Graham, the following response is given.
(2b) Once again, as detailed in the section supra, the teachings of Andreeff et al are not limited to leukemia. The document clearly references other cancers which include lung cancer that may be used with annamycin. The Examiner is including an evidentiary reference (Perez-Soler et al, Int. J. Cancer, 1997, Vol. 71, pages 35-41) to further support that it is well known in the art that liposomal annamycin may be used for lung cancers such as small cell lung cancer.
Perez-Soler et al is made of record as an evidentiary reference. The reference is directed to the use of liposomal annamycin in breast and small cell lung cancer cell lines (see entire document especially, abstract; pages 35-36, bridging paragraph). Thus, the evidentiary reference is consistent with the teaching of Andreeff et al which discloses that liposomal annamycin may be used in the treatment of lung cancer.
Applicant’s assertion (3) is summarized as follows: (3a) Andreeff et al’s reference to lung cancer was merely an aside and one of ordinary skill in the art would not conclude that liposomal annamycin was actually useful in the treatment of lung cancer. (3b) Applicant asserts that Andreeff et al only provided evidence of treating two patients with AML (acute promyelocytic leukemia) in Examples 1 and 2. Applicant concludes that primary and metastatic cancers in the lung are significantly different from AML and a skilled artisan would not have been reasonably motivated to modify Andreeff et al to arrive at the claimed invention.
As detailed supra, based on the teachings of Andreeff et al, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the pending invention to include lung cancer as a cancer treatable with liposomal annamycin. Once again, a reference is not limited to its preferred embodiments, but must be considered for what it teaches as a whole. Thus, the teachings regarding lung cancer disclosed in Andreeff et al should not be overlooked.
Assertion (4) is summarized as follows: (4a) impermissible hindsight was used in examining this application. As a result, it is asserted that Andreeff et al does not provide the missing motivation or establish a reasonable expectation of success to the presently claimed invention. (4b) In addition, it is asserted that the Examiner did not take into account the unexpected, surprising results included in the specification. Applicant’s make reference to Examples 1-4 and Figure 1-10.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Once again, Applicant’s attention is respectfully directed to each of the sections supra that detail the teachings of lung cancer in the cited prior art. As indicated above, hindsight was not used in generating the rejection. The teachings present in the primary reference were relied upon for teaching liposomal annamycin used in treating lung cancer. Furthermore, as disclosed in the evidentiary reference (Perez-Soler) made of record, it is known in the art that liposomal annamycin may be used for small cell lung cancer.
In regards to assertions that the Examiner did not take into account the unexpected, surprising results present in the specification, the following response is given. The cited prior art renders obvious the pending invention. As a result, the result are not unexpected that one is capable of treating lung cancer with liposomal annamycin. Both the cited prior art and the evidentiary reference illustrates that lung cancer is treatable with liposomal annamycin.
For the reasons set forth above, the cited prior art rejection is still deemed proper.
Conclusion
Claims 1, 3-13, 17-20, 22, 24, and 25 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
December 8, 2025