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 . 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.
Priority
The instant application is a 371 of PCT/US22/15905 filed on 02/10/2022 and claims domestic benefit to US provisional application no. 63/148,245 filed on 02/11/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/09/2023 and 11/13/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 01/30/2024 is acknowledged. Claims 1, 23, 25-32, and 38 are amended. Claims 10-22, 24, and 40 are cancelled. Claim 41 is newly added.
Accordingly, claims 1-9, 23, 25-39, and 41 are pending and being examined on the merits herein.
Claim Objections
Claim 4 and 39 are objected to because of the following informalities:
Claim 4 recites “wherein the sulfated glycosaminoglycan … active kills cancer stem cells … “. The recited “active” should be changed to “actively”.
Claim 39 recites “NH4+ … , 2-trimethylethanolammonium cation (choline), or a quaternary salt of isopropylamine … , and histidine.” The recited “and” should be changed to “or” to indicate the recited quaternary salts as alternatives.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 26, 28-29, 33-35, and 37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 26 and 28-29 recite “the modified hyaluronan”.
There is insufficient antecedent basis for this limitation in the claim because there is no prior recitation of a “modified hyaluronan”.
Claims 33-35 and 37 recite a specified range for the degree of methylation, average molecular weight, and/or degree of sulfation for the first and second modified hyaluronan. However, it is unclear if the first and second modified hyaluronan can be independently any amount in the recited range, or if both first and second modified hyaluronan need to the same amount in the recited range.
MPEP 2173.05(e) recites “The lack of clarity could arise where a claim refers to “said lever” or “the lever,” where the claim contains no earlier recitation or limitation of a lever and where it would be unclear as to what element the limitation was making reference. Similarly, if two different levers are recited earlier in the claim, the recitation of “said lever” in the same or subsequent claim would be unclear where it is uncertain which of the two levers was intended. A claim which refers to “said aluminum lever,” but recites only “a lever” earlier in the claim, is indefinite because it is uncertain as to the lever to which reference is made.”
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 23, 25-39, and 41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing the likelihood of a relapse of cancer, the growth or self-renewal of cancer stem cells, or the formation of quaternary spheroids, does not reasonably provide enablement for eliminating the likelihood of these limitations. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples, and
8) The quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, the breadth of the claims, and relative skill level
The invention relates to a method of preventing a relapse of cancer (claim 1) by administering the recited sulfated glycosaminoglycan as well as the recited compound being able to prevent the growth or self-renewal of cancer stem cells (claim 2) and/or prevent the formation of quaternary spheroids (claim 3).
The claims are broad in that they encompass eliminating the likelihood of a relapse of any cancer, cancer stem cell growth, and/or quaternary spheroid formation.
The instant specification provides a definition for the term “prevent” or “preventing” in paragraph 0027 on page 7, which recites “The term “prevent” or “preventing” as used herein is defined as eliminating or reducing the likelihood of the occurrence of one or more symptoms of a disease or disorder (e.g., relapse of cancer) when using the methods as described herein when compared to a control where the method is not used.”.
Therefore, “prevention” or "prevent" are the complete elimination of cancer relapse, cancer stem cell growth, and/or quaternary spheroid formation.
The relative skill of those in the art is high, that of an MD or PHD, someone with experience in the recited disease.
The amount of direction or guidance provided and the presence or absence of working examples
Applicant demonstrates in Example 1 (paragraphs 116-123) that a species of the recited sulfated glycosaminoglycan, GM-1111, was effective in inhibiting the growth of cancer stem cell spheroids from various cancer cell lines as seen in Table 1 (paragraph 0120) and Table 2 (paragraph 0121). Applicant further discloses that cancer stem cells can remain dormant but retain the ability to proliferate at an opportune time in the future causing cancer relapse.
However, the instant disclosure does not identify a method that could be used by one of ordinary skill in the art to determine that a subject would have predictably developed relapse of cancer, the growth or self-renewal of cancer stem cells without the claimed methods in order to establish that such recited conditions were prevented.
The described example suggests that the recited sulfated glycosaminoglycans were effective in reducing the likelihood of a relapse of cancer, the growth or self-renewal of cancer stem cells, or the formation of quaternary spheroid. However, the example does not demonstrate prevention of the recited conditions or a predictable method to identify patients who would have developed the recited conditions.
The state and predictability of the art
There are no art recognized methods that could be used to establish that cancer relapse was prevented using therapeutic treatment or to identify patients who would predictably develop a cancer relapse in order to predictably identify that prevention was achieved using therapeutic approaches. Rather, the art indicates that the recited diseases were not predictable.
Chang (in PTO-892) teaches that cancer stem cells (CSCs) are a class of pluripotent cells that have been observed in most types of solid and hematologic cancers, and further teaches the CSCs shown in numerous cancer models to be involved in tumor development, cell proliferation, and metastatic dissemination, while possessing a capacity for sustained self-renewal (see Abstract). Chang teaches that CSCs represent a small proportion of total cells in a given tumor, and exhibit resistance to chemotherapy and radiotherapy, which may promote “stemness” in nonstem cancer cells and may explain why successful therapeutic reduction of tumor bulk will often fail to produce clinical improvement (see Abstract). Chang illustrates in Figure 2 on page S22 models of CSC-driven tumor heterogeneity, highlighting the potential for multiple variations in manifestations of tumor propagation (see last paragraph right column page S21). Chang teaches that CSCs can potentially remain dormant for years and may result in cancer recurrence at a later time (see last paragraph right column page S21).
The teachings of Chang demonstrate that, while it was known that cancer stem cells can contribute to the relapse of cancer, these cancer stem cells represent a small subset population of the bulk tumor, are resistant to traditional radiotherapy and chemotherapy, and may develop tumors in a variety of ways including remaining dormant for years before recurrence of the cancer. These teachings demonstrate that there was no specific known cause of cancer relapse but rather a variety of ways in which cancer relapses. Therefore, these teachings suggest that there would be no method to predictably determine that a relapse in cancer would have developed in order to establish that it was prevented.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of a predictable method to identify patients who would develop cancer relapse, cancer stem cell growth, and/or quaternary spheroid formation, without treatment, one of ordinary skilled in the art would not be able to predictably use the claimed agent to eliminate the likelihood of the recited diseases. Furthermore, the quantity of experimentation to develop a method that could be used to prevent the recited conditions would be undue because a method to predictably identify a patient who would get the recited conditions does not exist and as described above, one of ordinary skill would have to further develop this method such that the recited method could then be used as a preventative measure against the recited conditions. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Interpretation
Claim 3 recites “prevents the formation of quaternary spheroids three generations after the administration of the sulfated glycosaminoglycan”.
The recited “three generations” is being interpreted as preventing quaternary spheroid formation from a primary spheroid (1°→4 spheroid formation) as disclosed in paragraph 00127-00128 in Example 3 of the instant specification.
The instant claims also recite an “alkyl group”.
The “alkyl group” is being interpreted as disclosed in the instant specification on paragraph 0025, which recites “The term “alkyl group” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl and the like. In one aspect, the alkyl group is a C1-C10 branched or straight chain alkyl group. In a further aspect, the alkyl group is methyl. The alkyl group can be unsubstituted or substituted. In the case when the alkyl group is substituted, one or more hydrogen atoms present on the alkyl group can be replaced with or more groups including, but not limited to, alkynyl, alkenyl, aryl, nitro, amino, ester, ketone, aldehyde, hydroxy, carboxylic acid, aralkyl, or alkoxy.”
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-9, 23, 25-39, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al. (US20050267069A1 in PTO-892) in view of Lee et al. (WO2019236453A1 in PTO-892).
Brown teaches methods and compositions for the treatment of cancer (see Abstract). Brown teaches their method involves administering a therapeutically effective amount of hyaluronan, or a derivative thereof, in conjunction with a chemotherapeutic agent such that said chemotherapeutic agent is more effective than when administered alone (see paragraph 0021). Brown teaches that administration of hyaluronan and a chemotherapeutic agent result in the suppression of tumor growth by at least 50%; preferably 60%; more preferably, greater than 70%, and even more preferably greater than 80%, 90% or 95%. Accordingly, the elimination of tumor growth and proliferation eliminates the production of multidrug resistant cells thereby reducing the recurrence of cancer and increasing the efficacy of chemotherapeutic treatments (paragraph 0025), which meets the limitation of “preventing a relapse of cancer” as recited in instant claim 1. Brown teaches that exemplary hyaluronic acid derivatives include sulfated hyaluronic acid and esters thereof and among others (see paragraph 0062).
Brown demonstrates in Example 3 the in vivo efficacy of hyaluronan in the treatment of human breast carcinomas (see paragraphs 0103-0138). Brown discloses that cell line MDA-MB-468 was selected as the cancer cell inoculant for the generation of any nude mouse human tumor xenografts, and mice were treatment with various HA and 5-FU dosing regimens as shown in Table 7 paragraph 0111. Brown discloses that the co-administration of HA resulted in a significant reduction in non-lymphoid metastasis. With the exception of the mice receiving the HA therapy, new tumors were observed around the neck or underarm region of the area adjacent to the primary tumor (see paragraph 0128). Brown also demonstrates in Example 7 (paragraphs 342-381) that the co-administration of HA and irinotecan was effective for treating colon cancer tumors. Brown shows in Table 10 paragraph 0381 that mice receiving Camptosar (irinotecan) / hyaluronic acid demonstrated sufficiently greater tumor regression than mice receiving the equivalent Camptosar dosage. Brown teaches that all co-administered animals had complete remission or partial response versus a 28% of the animals treated with Camptosar alone. Lastly, Brown demonstrates in Example 8 that HA altered the morphology of human breast cancer cells that appeared to be undergoing apoptosis (see paragraph 0388), and further shows that HA reduced the tumor volume in vivo (paragraph 0390 and FIG. 9A-9B). Brown teaches that the anti-proliferative effect could be due to the degradation of the HA into apoptotic-inducing fragments and/or the microembolisation effect, which could result in tissue hypoxia and subsequent cell death (see paragraph 0390).
Even though Brown suggests the use of sulfated hyaluronic acid for treating a cancer and further reducing the recurrence of cancer in a subject, Brown does not teach that the sulfated hyaluronic acid contains at least one primary C-6 hydroxyl position of an N-acetylglucosamine residue comprising an alkyl group such as methyl. Furthermore, Brown does not teach the recited kDa, degree of sulfation, and the two modified hyaluronans in instant claim 32.
Lee teaches methods for preventing serious health consequence and/or tissue damage in a subject after the subject has been exposed to ionizing radiation and/or chemotherapy by administering to the subject a sulfated polysaccharide or the pharmaceutically acceptable salt or ester thereof (see Abstract). Lee teaches that cancer patients undergoing radiation therapy and chemotherapy can suffer from a number of different types of mucositis, which is an inflammatory disease of a mucosal tissue (see page 1 third paragraph). Lee teaches that oral mucositis progresses from erythema within a week after cancer therapy and quickly turns into ulcerative lesions with opportunistic infections causing severe pain and difficulty in eating (see page 1 third paragraph).
Lee teaches that administration of a sulfated polysaccharide to a subject after exposure to ionizing radiation and/or chemotherapy unexpectedly prevents or significantly prevents or reduces a serious health consequence such as acute radiation syndrome (ARS) and/or tissue damage such as mucositis (see page 13 last paragraph through page 14 first three paragraph).
Lee further teaches that the sulfated polysaccharide or a pharmaceutically acceptable salt or ester thereof comprises hyaluronan comprising at least one sulfate group and at least one primary C-6 hydroxyl position of an N-acetyl-glucosamine residue comprising an alkyl group or fluoroalkyl group (see claim 45). Lee teaches that the modified hyaluronan has an unsubstituted C1-C10 alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl; the sulfate group is at the C-2 or C-3 hydroxyl position of a glucuronic acid moiety having a degree of sulfation from 0.5 to 3.5 per disaccharide unit; and the modified hyaluronan has a molecular weight of 2 kDa to 10 kDa (claim 56). Lee teaches that 1 % to 100% of the primary C-6 hydroxyl protons of the N-acetyl-glucosamine residue are substituted with an alkyl group or fluoroalkyl group (see claim 49). Lee teaches that the sulfated hyaluronan has an average molecular size from 10 kDa to 2000 kDa (claim 50). Lee teaches that the pharmaceutically acceptable salt of their sulfated polysaccharides includes NH4+, Na+, and among others (see claim 58). Lee teaches that their sulfated polysaccharides can be administered subcutaneously or intravenously (see claim 23).
Lee teaches that the hyaluronan can be modified with a sulfating agent to produce the partially or fully sulfated hyaluronan (see second to last paragraph page 25). Lee teaches that the sulfating agent is a pyridine-sulfur trioxide complex, where the pyridine is covalently attached to the sulfated hyaluronan (see last paragraph page 25 through first paragraph page 26). Lee teaches that 0.15% to 2.5% of the sulfated hyaluronan has pyridine covalently attached to the molecule (see first paragraph page 26).
Lee demonstrates the use of a modified hyaluronan, referred to as GM-1111, which is a sulfated hyaluronan methylated at the primary C-6 hydroxyl position of an N-acetyl-glucosamine residue and having a molecular weight of approximately 5.5 kDa (see section “I. Administration of Modified Hyaluronan Pre- and Post-Irradiation” on pages 34-40). Here, the GM-1111 compound of Lee is the same GM-1111 compound recited in the instant specification in paragraph 00115 on pages 29-30. Lee demonstrates in this example that GM-1111 had anti-inflammatory effects and significant radiation mitigating effects when administered to mice exposed to X-ray irradiation (see Conclusion section on page 40). Lee further teaches that unmodified HA did not show any measurable therapeutic benefits (see Conclusion section first paragraph on page 38)
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the hyaluronic acid in Brown with the sulfated hyaluronans of Lee for treating and reducing the recurrence of a tumor such as breast or colon tumors to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification because Lee provides guidance of using the same sulfated hyaluronans such as the GM-1111 compound that have an added advantage of reducing a serious health consequence such as acute radiation syndrome (ARS) and/or tissue damage such mucositis for cancer patients who have received ionizing radiation and/or chemotherapy. Therefore, an ordinary skilled would have been motivated to use sulfated hyaluronans in order to obtain the advantage disclosed in Lee. Furthermore, one of ordinary skill in the art would have made this modification with a reasonable expectation of success because Brown establishes using hyaluronan and its derivatives such as sulfated hyaluronan in combination with chemotherapy agents for treating and reducing the recurrence of cancer tumors such as colon tumor. Therefore, an ordinary skilled artisan could have predictably considered alternative sulfated hyaluronans such as the sulfated hyaluronans disclosed in Lee with a reasonable expectation of success.
In regards to instant claims 2-3, even though the combined teachings of Brown and Lee described above do not teach the recited “prevent the growth or self-renewal of cancer stem cells in a subject” as well as the recited “prevents the formation of quaternary spheroids three generations after … “, these prevention results would naturally flow from the combined teachings of Brown and Lee described above because the combined teachings provide guidance of administering the same sulfated hyaluronan which is the GM-1111 compound to treat the same cancer patient population such as a breast or colon tumor patient and further reducing the recurrence of the cancer as described above. MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
In regards to instant claim 5, it would have also been prima facie obvious before the effective filing date of the claimed to have used the modified method as disclosed by the combined teachings of Brown and Lee described above for a subject that was previously treated for a cancer such as ionizing radiation and/or chemotherapy as disclosed in the Lee. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Lee provides guidance of administering sulfated hyaluronans to patients that have been exposed to ionizing radiation and/or chemotherapy.
In regards to instant claims 32-38, it would have also been prima facie obvious before the effective filing date of the claimed to have modified the method as disclosed by the combined teachings of Brown and Lee described above by further combining a sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee with a covalently bonded pyridine sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee. One of ordinary skill in the art would have made this combination with a reasonable expectation of success because the combined teachings of Brown and Lee disclose that both sulfated hyaluronans are useful for the same purpose of treating a cancer and reducing the recurrence of a tumor. See In re Kerkhoven, MPEP 2144.06 I.
Furthermore, it would have been prima obvious before the effective filing date of the claimed invention to have arrived at the recited degree of methylation, the recited degree of sulfation, and the recited amount of pyridine present for the two sulfated hyaluronans as disclosed by the combined teachings of Brown and Lee described above because Lee teaches an overlapping range for the degree of methylation (1 % to 100%, equal 0.1 to 1), the degree of sulfation (0.5 to 3.5), and the amount of pyridine present (0.15% to 2.5%). See MPEP 2144.05 I.
In regards to instant claims 39 and 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered the sulfated hyaluronan as disclosed by the combined teachings of Brown and Lee described above as a pharmaceutically acceptable salt such as NH4+ as disclosed in Lee and either subcutaneously or intravenously as disclosed in Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Lee provides guidance that the described pharmaceutically acceptable salt forms and mode of administration are suitable to treat the same cancer patient populations.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 23, 25-39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,642,366 (‘366) in view of Brown et al. (US20050267069A1 in PTO-892) and Lee et al. (WO2019236453A1 in PTO-892).
The claims of ‘366 recite a method for preventing a serious health consequence, tissue damage, or a combination thereof in a subject exposed to ionizing radiation, chemotherapy, or a combination thereof comprising administering to the subject a sulfated polysaccharide or a pharmaceutically acceptable salt or ester thereof after the subject has been exposed to ionizing radiation, chemotherapy, or a combination thereof, wherein the sulfated polysaccharide or a pharmaceutically acceptable salt or ester thereof comprises a modified hyaluronan or a pharmaceutically acceptable salt or ester thereof, wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester comprises (a) a sulfated hyaluronan or the pharmaceutically acceptable salt or ester thereof or (b) hyaluronan comprising at least one sulfate group and at least one primary C-6 hydroxyl position of an N-acetyl-glucosamine residue comprising an alkyl group or fluoroalkyl group.
The difference between the claims of ‘366 and the claimed invention is that the claims of ‘366 do not recite a method for preventing a relapse in cancer as well as the recited kDa, degree of sulfation, and the two modified hyaluronans in instant claim 32.
The independent teachings of Brown and Lee are as described above.
It would have been prima facie obvious before the effective filing date of the claim invention to have further used the method recited in the claims of ‘366 for a method of preventing a relapse in colon cancer in a patient being treated for chemotherapy as suggested by Brown and Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Brown provides guidance of using hyaluronan and its derivatives such as sulfated hyaluronan in combination with chemotherapy agents for treating and reducing the recurrence of cancer tumors such as colon tumor, and Lee provides guidance of using the same sulfated hyaluronans that have the same added advantage of reducing a serious health consequence such as acute radiation syndrome (ARS) and/or tissue damage such mucositis for cancer patients who have received ionizing radiation and/or chemotherapy. Therefore, an ordinary skilled could have predictably used the sulfated hyaluronans recited in the claims of ‘366 for preventing a relapse in cancer.
In regards to instant claims 2-3, even though the combination of the claims of ‘366 and the teachings of Brown and Lee described above do not recite “prevent the growth or self-renewal of cancer stem cells in a subject” as well as the recited “prevents the formation of quaternary spheroids three generations after … “, these prevention results would naturally flow from the combination of the claims of ‘366 and the teachings of Brown and Lee described above because the combined references provide guidance of administering the same sulfated hyaluronan to treat the same cancer patient population such as a colon tumor patient and further reducing the recurrence of the cancer as described above. MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
In regards to instant claim 5, it would have also been prima facie obvious before the effective filing date of the claimed to have used the modified method as disclosed by the combination of the claims of ‘366 and the teachings of Brown and Lee described above for a subject that was previously treated for a cancer such as ionizing radiation and/or chemotherapy as disclosed in the Lee. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Lee provides guidance of administering sulfated hyaluronans to patients that have been exposed to ionizing radiation and/or chemotherapy.
In regards to instant claims 25-31, it would have also been prima facie obvious before the effective filing date of the claimed invention to have arrived at the recited range of primary C-6 hydroxyl substituted with an alkyl group, the recited molecular weight ranges in instant claims 36 and 31, the alkyl group being methyl, and the recited degree of sulfation because Lee teaches an overlapping range for the degree of methylation (1 % to 100%, equal 0.1 to 1), the degree of sulfation (0.5 to 3.5), the molecular weights (2-10 kDa and 10-2000 kDa), and that the alkyl group on sulfated hyaluronan can be methyl. See MPEP 2144.05 I.
In regards to instant claims 32-38, it would have also been prima facie obvious before the effective filing date of the claimed to have modified the method as disclosed by the combination of the claims of ‘366 and the teachings of Brown and Lee described above by further combining a sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee with a covalently bonded pyridine sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee. One of ordinary skill in the art would have made this combination with a reasonable expectation of success because the combination of the claims of ‘366 and the teachings of Brown and Lee described above provide guidance that both sulfated hyaluronans are useful for the same purpose of treating a cancer and reducing the recurrence of a tumor. See In re Kerkhoven, MPEP 2144.06 I.
Furthermore, it would have been prima obvious before the effective filing date of the claimed invention to have arrived at the recited degree of methylation, the recited degree of sulfation, and the recited amount of pyridine present for the two sulfated hyaluronans as disclosed by the combination of the claims of ‘366 and the teachings of Brown and Lee described above because Lee teaches an overlapping range for the degree of methylation (1 % to 100%, equal 0.1 to 1), the degree of sulfation (0.5 to 3.5), and the amount of pyridine present (0.15% to 2.5%). See MPEP 2144.05 I.
In regards to instant claims 39 and 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered the sulfated hyaluronan as disclosed by the combination of the claims of ‘366 and the teachings of Brown and Lee described above as a pharmaceutically acceptable salt such as NH4+ as disclosed in Lee and either subcutaneously or intravenously as disclosed in Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Lee provides guidance that the described pharmaceutically acceptable salt forms and mode of administration are suitable to treat the same cancer patient populations.
Claims 1-9, 23, 25-39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,109,225 (‘225) in view of Brown et al. (US20050267069A1 in PTO-892) and Lee et al. (WO2019236453A1 in PTO-892).
The claims of ‘255 recite a method for reducing or maintaining the size of a tumor in a subject, the method comprising exposing the tumor to ionizing radiation and administering subcutaneously or intravenously to the subject a pharmaceutical composition comprising a modified hyaluronan or a pharmaceutically acceptable salt or ester, wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester comprises hyaluronan with at least one primary C-6 hydroxyl position of an N-acetylglucosamine residue substituted with a methyl group, and at least one C-2 hydroxyl proton, at least one hydroxyl proton, or at least one C-3 hydroxyl proton and at least one hydroxyl proton is substituted with a sulfate group, and the modified hyaluronan or its pharmaceutically acceptable salt or ester has an average molecular weight of 2 kDa to 10 kDa. The claims of ‘255 recite wherein the pharmaceutically acceptable salt is selected from the group consisting of NH4 + and among others (claim 2), wherein the modified hyaluronan is administered to the subject after the tumor is exposed to ionizing radiation, before the tumor is exposed to ionizing radiation, or a combination thereof or while being exposed (claim 3), wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has a degree of methylation from 0.03 to 0.50 (claim 8), wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has a degree of sulfation of 3.0 to 4.0 sulfate groups per disaccharide unit (claim 10), and herein the modified hyaluronan or its pharmaceutically acceptable salt or ester has from 50% to 100% of the primary C-6 hydroxyl protons of the N-acetyl-glucosamine residue of the modified hyaluronan are replaced with a methyl group (claim 9).
The difference between the claims of ‘255 and the claimed invention is that the claims of ‘255 do not recite a method for preventing a relapse in cancer.
The independent teachings of Brown and Lee are as described above.
It would have been prima facie obvious before the effective filing date of the claim invention to have further used the method recited in the claims of ‘255 for a method of preventing a relapse in colon cancer in a patient being treated for chemotherapy as suggested by Brown and Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Brown provides guidance of using hyaluronan and its derivatives such as sulfated hyaluronan in combination with chemotherapy agents for treating and reducing the recurrence of cancer tumors such as colon tumor, and Lee provides guidance of using the same sulfated hyaluronans that have the same added advantage of reducing a serious health consequence such as acute radiation syndrome (ARS) and/or tissue damage such mucositis for cancer patients who have received ionizing radiation and/or chemotherapy. Therefore, an ordinary skilled could have predictably used the sulfated hyaluronans recited in the claims of ‘255 for preventing a relapse in cancer.
In regards to instant claims 2-3, even though the combination of the claims of ‘255 and the teachings of Brown and Lee described above do not recite “prevent the growth or self-renewal of cancer stem cells in a subject” as well as the recited “prevents the formation of quaternary spheroids three generations after … “, these prevention results would naturally flow from the combination of the claims of ‘255 and the teachings of Brown and Lee described above because the combined references provide guidance of administering the same sulfated hyaluronan to treat the same cancer patient population such as a colon tumor patient and further reducing the recurrence of the cancer as described above. MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
In regards to instant claim 5, it would have also been prima facie obvious before the effective filing date of the claimed to have used the modified method as disclosed by the combination of the claims of ‘255 and the teachings of Brown and Lee described above for a subject that was previously treated for a cancer such as ionizing radiation and/or chemotherapy as disclosed in the Lee. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Lee provides guidance of administering sulfated hyaluronans to patients that have been exposed to ionizing radiation and/or chemotherapy.
In regards to instant claims 25-31, it would have also been prima facie obvious before the effective filing date of the claimed invention to have arrived at the recited range of primary C-6 hydroxyl substituted with an alkyl group, the recited molecular weight ranges in instant claims 36 and 31, the alkyl group being methyl, and the recited degree of sulfation because Lee teaches an overlapping range for the degree of methylation (1 % to 100%, equal 0.1 to 1), the degree of sulfation (0.5 to 3.5), the molecular weights (2-10 kDa and 10-2000 kDa), and that the alkyl group on sulfated hyaluronan can be methyl. See MPEP 2144.05 I.
In regards to instant claims 32-38, it would have also been prima facie obvious before the effective filing date of the claimed to have modified the method as disclosed by the combination of the claims of ‘255 and the teachings of Brown and Lee described above by further combining a sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee with a covalently bonded pyridine sulfated methyl hyaluronan with an average molecular weight of 2 kDa to 10 kDa as disclosed in Lee. One of ordinary skill in the art would have made this combination with a reasonable expectation of success because the combination of the claims of ‘255 and the teachings of Brown and Lee described above provide guidance that both sulfated hyaluronans are useful for the same purpose of treating a cancer and reducing the recurrence of a tumor. See In re Kerkhoven, MPEP 2144.06 I.
Furthermore, it would have been prima obvious before the effective filing date of the claimed invention to have arrived at the recited degree of methylation, the recited degree of sulfation, and the recited amount of pyridine present for the two sulfated hyaluronans as disclosed by the combination of the claims of ‘255 and the teachings of Brown and Lee described above because Lee teaches an overlapping range for the degree of methylation (1 % to 100%, equal 0.1 to 1), the degree of sulfation (0.5 to 3.5), and the amount of pyridine present (0.15% to 2.5%). See MPEP 2144.05 I.
In regards to instant claims 39 and 41, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered the sulfated hyaluronan as disclosed by the combination of the claims of ‘255 and the teachings of Brown and Lee described above as a pharmaceutically acceptable salt such as NH4+ as disclosed in Lee and either subcutaneously or intravenously as disclosed in Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Lee provides guidance that the described pharmaceutically acceptable salt forms and mode of administration are suitable to treat the same cancer patient populations.
Claims 1-9, 23, 25-39, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-39 of copending Application No. 18/817,657 (‘657) in view of Brown et al. (US20050267069A1 in PTO-892) and Lee et al. (WO2019236453A1 in PTO-892).
The claims of ‘657 recite a method for reducing or maintaining the size of a tumor in a subject, the method comprising exposing the tumor to ionizing radiation and administering to the subject a pharmaceutical composition comprising a modified hyaluronan or a pharmaceutically acceptable salt or ester, wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester comprises hyaluronan with at least one primary C-6 hydroxyl position of an N-acetyl-glucosamine residue substituted with a methyl group, and at least one C-2 hydroxyl proton, at least one hydroxyl proton, or at least one C-2 hydroxyl proton and at least one hydroxyl proton is substituted with a sulfate group, and the modified hyaluronan or its pharmaceutically acceptable salt or ester has an average molecular weight of 2 kDa to 10 kDa.
The difference between the claims of ‘657 and the claimed invention is that the claims of ‘657 do not recite a method for preventing a relapse in cancer.
The independent teachings of Brown and Lee are as described above.
It would have been prima facie obvious before the effective filing date of the claim invention to have further used the method recited in the claims of ‘657 for a method of preventing a relapse in colon cancer in a patient being treated for chemotherapy as suggested by Brown and Lee to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Brown provides guidance of using hyaluronan and its derivatives such as sulfated hyaluronan in combination with chemotherapy agents for treating and reducing the recurrence of cancer tumors such as colon tumor, and Lee provides gui