DETAILED ACTION
Examiner acknowledges receipt of the reply filed 6/10/2026, in response to the restriction requirement mailed 4/10/2026.
Claims 1-47, 54-100, 102-110, 118, 130, and 133-149 are pending. Claims 48-53, 101, 111-117, 119-129, 131, and 132 have been cancelled. Claims 133-149 are newly added.
Claims 1, 2, 5, 7-21, 23-38, 41-47, 59-62, 71, 77-80, 94, 96, 99, 100, 107-110, and 138-141 are withdrawn from further prosecution for the reasons set forth below.
Claims 3, 4, 6, 22, 39, 40, 54-5, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are being examined on the merits in this office 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 .
Priority
The filing receipt dated 7/16/2025 provides the following information:
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Election/Restrictions
Applicant’s election of Group 2 without traverse in the reply filed on 6/10/2026 is acknowledged. Claims 3, 4, 6, 22, 39, 40, 71-95, 97, and 98 are included in Group 2. Claims 54-70, 102-110, 118, and 130 have been amended to depend from claims 3, 4, or 6. New claims 133-149 depend from claims 3 or 4.
Claims 1, 2, 5, 7-21, 23-38, 41-47, 99, and 100 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/10/2026.
Applicant’s election of the following species without traverse in the reply filed on 6/10/2026 is acknowledged:
Saposin C polypeptide- 100% identity
Phospholipid- phosphatidylserine
neuropathic symptom- pain
type of cancer – gastrointestinal cancer
chemotherapeutic/ antineoplastic agent- oxaliplatin
Claims 3, 4, 6, 22, 39, 40, 54-55, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 read on the elected species.
Claims 59-62, 71, 77-80, 94, 107-110, and 138-141 are withdrawn from further consideration pursuant to as being drawn to a nonelected species. Election was made without traverse in the reply filed on 6/10/2026.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The abstract of the disclosure is objected to for the following minor informality:
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Here, the abstract recites: “disclosed herein are methods for reducing” at line 1.
Claim Objections
Claims 3, 6, 54-56, 61, 64, 65, 102-104, 133-135, and 144 are objected to because of the following informalities:
Claim 3 should be amended to recite: “administering to the subject in need thereof”.
Claim 6 should be amended to recite: “comprising administering to the subject in need thereof”.
Claims 54-56 should be amended to recite: “saposin C
Claim 61 should be amended to recite: “of claim 57, wherein the phosphatidylserine
Claim 64 should be amended to depend from 63 because it narrows the limitations of claim 63.
Claim 65 should be amended to depend from 64 because it narrows the limitations of claim 64.
Claims 102-104 should be amended to recite: “saposin C
Claims 133-135 should be amended to recite: “saposin C
Claim 144 should be amended to depend from 143 because it narrows the limitations of claim 143.
Appropriate correction is required.
Claim 71 recites an acronym that should be written out in full name in the first order of appearance within the claims.
Claim interpretation
It is noted that the instant specification indicates that gastrointestinal cancer includes esophageal cancer, gastric cancer, anal cancer, colorectal cancer, bowel cancer, gallbladder cancer, pancreatic cancer, liver cancer, islet cell cancer, rectal cancer, small intestine cancer, gastrointestinal carcinoid tumors, or gastrointestinal stromal tumors (as-filed specification at p. 8, ll. 27-31).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 22, 39, 40, 54-58, 63-70, 87, 88, 91, 98, 118, 130, 133-137, and 142-149 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.
Claim 3 recites the limitation "the incidence”. There is insufficient antecedent basis for this limitation in the claim.
Because claims 22, 39, 40, 54-58, 63-70, and 145-149 depend from indefinite claim 3 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Claim 4 recites the limitation "the incidence” at line 7. There is insufficient antecedent basis for this limitation in the claim.
Because claims 118, 130, depend from indefinite claim 4 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Claims 63-65 recite the limitation "the molar ratio”. There is insufficient antecedent basis for this limitation in the claim.
Claim 87 recites the limitation “the first four weeks". There is insufficient antecedent basis for this limitation in the claim.
Claim 88 recites the limitation “the first two weeks". There is insufficient antecedent basis for this limitation in the claim.
Claim 91 recites the limitation “the first 24 weeks". There is insufficient antecedent basis for this limitation in the claim.
Claim 98 recites the limitation “the treatment". There is insufficient antecedent basis for this limitation in the claim.
Claims 142-144 recite the limitation "the molar ratio”. There is insufficient antecedent basis for this limitation in the claim.
Claim clarification is required.
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 4, 130, 133-137, and 142-44 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 treating gastrointestinal cancer comprising SapC-DOPS, does not reasonably provide enablement for all iterations of cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification 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, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
By way of background, four cases are of particular relevance to the question of enablement of a method of treating cancers broadly or even generally:
In In re Buting, 418 F.2d 540, 163 USPQ 689 (CCPA 1969), the claim was drawn to “The method of treating a malignant condition selected from the group consisting of leukemias, sarcomas, adenocarcinomas, lymphosarcomas, melanomas, myelomas, and ascitic tumors” using a small genus of compounds. The Court decided that human testing “limited to one compound and two types of cancer” was not “commensurate with the broad scope of utility asserted and claimed”.
In Ex parte Jovanovics, 211 USPQ 907 (Bd. Pat. App. & Inter. 1981) the claims were drawn to “the treatment of certain specified cancers in humans” by the use of a genus of exactly two compounds, the N-formyl or N-desmethyl derivative of leurosine. Applicants submitted “affidavits, publications and data” for one of the compounds, and a dependent claim drawn to the use of that species was allowed. For the other, no data was presented, applicants said only that the other derivative would be expected to be less effective; claims to the genus were refused.
In Ex parte Busse, et al., 1 USPQ2d 1908 (Bd. Pat. App. & Inter. 1986) claims were drawn to “A therapeutic method for reducing metastasis and neoplastic growth in a mammal” using a single species. The decision notes that such utility “is no longer considered to be “incredible”, but that “the utility in question is sufficiently unusual to justify the examiner's requirement for substantiating evidence. Note also that there is also a dependent claim 5 which specified “wherein metastasis and neoplastic growth is adenocarcinoma, squamous cell carcinoma, melanoma, cell small lung or glioma.” The decision notes that “even within the specific group recited in claim 5 some of the individual terms used actually encompass a relatively broad class of specific types of cancer, which types are known to respond quite differently to various modes of therapy.”
In Ex parte Stevens, 16 USPQ2d 1379 (Bd. Pat. App. & Inter. 1990) a claim to “A method for therapeutic or prophylactic treatment of cancer in mammalian hosts” was refused because there was “no actual evidence of the effectiveness of the claimed composition and process in achieving that utility.”
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) Breadth of claims. The claims are drawn to a method of treating cancer, the method comprising co-administering to a human subject in need thereof a chemotherapeutic agent that is associated with neuropathic symptom side effects; and a nanovesicle formulation comprising (i) a saposin C polypeptide comprising SEQ ID NO: 1 with zero to four amino acid insertions, substitutions, deletions, or combination thereof, and (ii) a phospholipid having a net negative charge at neutral pH, wherein the nanovesicle formulation is administered in an amount that reduces the incidence, intensity, and/or duration of the neuropathic symptom side effects associated with the chemotherapeutic agent, or delays onset of the neuropathic symptom side effects associated with the chemotherapeutic agent.
There are many different types of cancers, but all share one hallmark characteristic: unchecked growth that progresses toward limitless expansion (National Institute of Cancer- understanding and related topics, accessed 8/21/2014 at URL: cancer.gov/cancertopics/understandingcancer at p. 2). Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. Id. Examiner notes that the following prior art is a selection of the recited forms of cancer.
A. Lung carcinoma is the leading cause of cancer-related death worldwide (Merck Manuals Lung Carcinoma accessed 3/12/2017 at URL merckmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma). About 85% of cases are related to cigarette smoking. Id. Treatment varies by cell type and by stage of disease. Primary treatments include surgery (depending on cell type and stage), chemotherapy and radiation therapy. Id.
B. Brain Tumors are noncancerous (benign) or cancerous (malignant) growth in the brain. It may originate in the brain or have spread (metastasized) to the brain from another part of the body (Merck Manuals Brain Tumors accessed 8/21/2014 at URL Merckmanuals.com/home/brain_spinal_cord_and_nerve_disorders/). Brain tumors—whether cancerous or not—can cause serious problems because the skull is rigid, providing no room for the tumor to expand. Also, tumors may develop near parts of the brain that control vital functions and cause problems. There are two main types of brain tumors. Primary tumors originate in the cells within or next to the brain. They may be cancerous or noncancerous. Secondar tumors are metastases. That is, they originate in another part of the body and spread to the brain. Thus, they are always cancerous. The most common type of primary cancerous brain tumor is a glioma, which has several subtypes. Gliomas account for 65% of all primary brain tumors. However, most cancerous brain tumors are secondary—metastases from cancer that started in another part of the body. Doctors consider the possibility of a brain tumor in people who have had a seizure for the first time or who have characteristic symptoms. Although doctors can often detect brain dysfunction during an examination, other procedures are needed to diagnose a brain tumor. Magnetic resonance imaging (MRI) is the best test for identifying brain tumors. Computed tomography (CT) is a good alternative. Treatment of a brain tumor depends on its location and type. When possible, the tumor is removed surgically in a procedure called craniotomy (which involves opening the skull). Some brain tumors can be removed with little or no damage to the brain. However, many grow in an area that makes removal by traditional surgery difficult or impossible without destroying essential structures.
C. There are many types of colorectal cancers. See, e.g., Merck Manual Colorectal Cancer accessed 8/21/2014 at URL merckmanuals.com/home/digestive_disorders/tumors_of_the_digestive_system/colorectal_cancer.html). Almost all cancers of the large intestine and rectum (colorectal) are adenocarcinomas, which develop from the lining of the large intestine (colon) and rectum. Id. In Western countries, cancer of the large intestine and rectum is one of the most common types of cancer and the second leading cause of cancer death. Id. Colon cancer is more common among women, and rectal cancer is more common among men. Id.
D. Breast cancer is the second most common cancer among women after skin cancer and, of cancers, is the second most common cause of death among women after lung cancer. There are many types of breast cancer. See e.g., Merck Manual Breast Cancer accessed 8/21/2014 at URL: merckmanuals.com/home/womens_health_issues/breast_disorders/breast_cancer. Several factors affect the risk of developing breast cancer. Thus, for some women, the risk is much higher or lower than average. Most factors that increase risk, such as age and certain abnormal genes, cannot be modified. However, regular exercise, particularly during adolescence and young adulthood may reduce the risk of developing
Breast cancer. Smoking, regularly drinking alcoholic beverages, and using hormone therapy with estrogen and progesterone may increase the risk. treatment begins after the woman's condition has been thoroughly evaluated, about a week or more after the biopsy. Treatment options depend on the stage and type of breast cancer and the receptors that the cancer has. However, treatment is complex because the different types of breast cancer differ greatly in characteristics such as growth rate, tendency to spread (metastasize), and response to various treatments. Also, much is still unknown about breast cancer. Consequently, doctors may have different opinions about the most appropriate treatment for a particular woman.
E. Thyroid cancer. There are four general types of thyroid cancer (papillary, follicular, medullary, and anaplastic) (Thyroid cancer accessed 3/12/2017 at URL merckmanuals.com/professional/endocrine-and-metabolic-disorders/thyroid-disorders/thyroid-cancers). Most thyroid cancers manifest as asymptomatic nodules. Id. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid cancers. Id. Diagnosis is often by fine-needle aspiration biopsy but may involve other tests. Id. Treatment is surgical removal, usually followed by ablation of residual tissue with radioactive iodine. Id.
F. Renal Cancer. Renal cell carcinoma (RCC) is the most common renal cancer, accounting for 90 to 95% of primary malignant renal tumors (Renal cell carcinoma, accessed 3/12/2017 at URL merckmanuals.com/professional/genitourinary-disorders/genitourinary-cancer/renal-cell-carcinoma). Id. Symptoms (most often gross or microscopic hematuria) usually do not develop until the tumor is large or metastatic, so incidental discovery is common. Id. Diagnose of RCC is by MRI or contrast-enhanced CT, as well as testing of liver function. Id. Treatment of localized RCC is by radical nephrectomy, whereas advanced RCC is treated by palliative surgery, radiation therapy, targeted drug therapies, and/or interferon alfa-2b or IL-2. Id.
G. Bladder Cancer. Most bladder cancers are of a type called transitional cell, affecting the same kinds of cells (transitional cells) that are usually the cancerous cells responsible for renal pelvis and ureter cancers. See e.g., Merck Manual Bladder Cancer accessed 8/21/2014 at URL: merckmanuals.com/home/kidney_and_urinary_tract_disorders/cancers_of_the_kidney_and_genitourinary_tract/bladder_cancer.html. More than 70,000 new cases of bladder cancer are diagnosed every year in the United States and about 15,000 people die of bladder cancer every year. Id. About 3 times as many men as women develop bladder cancer. Smoking is the greatest single risk factor and seems to be one of the causes in at least half of all new cases. Id.
(2) The nature of the invention and predictability in the art: With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] …anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(3) Direction or Guidance: The guidance provided is limited. The examples are limited to SapC-DOPS (one form of phospholipid) and gastrointestinal cancer (e.g., colorectal).
The skilled artisan does not have sufficient guidance to extrapolate the limited teachings from limited forms of phospholipids (SapC-DOPS) and gastrointestinal cancer
to different phospholipids and all forms of cancer (body location and disease etiologies). The skilled artisan cannot predict which of the highly variable types of cancer known in the art would be suitable for treatment with the claimed compounds, much less dosage amounts and routes of administration. Accordingly, the specification provides little guidance over the scope of the presently pending claims.
(4) State of the Prior Art: A review of the relevant art yielded a diverse array of treatment options for those suffering from various forms of cancer. Traditional therapies include chemotherapy, radiotherapy and surgery.
Chu et al (PLoS One: 8-10:1-11 (Oct 2013)- cited in IDS filed 1/15/2025) teaches the lysosomal protein (saposinC, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS) are assembled into nanovesicles (SapC-DOPS) for treating pancreatic cancer.
So far as the examiner is aware, applicants’ recited saposin C, has not been successfully used treating all possible cancers, and also there is no known single compound or genus (having common core structure) that treats all possible cancers.
(5) Working Examples: Example 1 discloses treatment of cancer patients improvement of neuropathy (e.g., pain, peripheral neuropathy, numbness, tingling). Example 2 discloses treatment of neuropathic symptoms in a mouse model of chemotherapy (oxaliplatin)-induced peripheral neuropathy (e.g., cold hypersensitivity and pain). Example 3 is a prophetic example of a clinical trial relating to treatment/assessment of oxaliplatin-induced sensory neuropathy in colorectal carcinoma. Example 4 discloses and in vitro assay of neuronal protection by BXQ-350 (claimed nanovesicle formulation comprising saposin C and a phospholipid/SapC-DOPS). Example 5 discloses an in vitro assay of neuroprotection in the presence of chemotherapeutics (e.g., oxaliplatin and vincristine).
Example 6 discloses that SapC-DOPS enhances the cytotoxic effects of oxaliplatin and 5-fluoracil in a colorectal cancer cell line. Of note, Example 6 states: “BXQ-315 with oxaliplatin shows little cytotoxicity compared to the triple combination [BXQ-350 + oxaliplatin + 5-fluoracil] which is very good lethality”.
Example 7 discloses that SapC-DOPS and FOLFOX is more beneficial than FOLFOX alone. Example 8 indicates that BXQ-350 repolarizes macrophages towards the M1 antitumor genotype ex vivo. Example 9 asserts that BXQ-350- in combination with activated cytotoxic T cells, stimulates the killing effects of T cells. Example 10 that SapC-DOPS and immunity checkpoint inhibitor [anti-PD1 Ab] is more effective at treating colon cancer than either agent alone. Example 11 indicates that BXQ-350 reduces the suppressive nature of myelinated derived suppressor cells towards T cells. Example 12 indicates that BXQ-350 positively influences and rebalances the immune system toward an antitumor state.
Cancers that were treated were limited to gastrointestinal cancers. The only form of phospholipid was DOPS.
(6) Skill of those in the art: The relative skill of those in the art is high. MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
An ordinary artisan in the area of drug development would have experience in screening compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against particular biological target is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems such as cancer.
Determining how a particular compound will impact cancer is not routine. There is no chemical targeting system at this time that can directly stimulate or block only a highly divergent cancer(s), while avoiding effects on other parts of the cells, where the same signal may have a different and unwanted effect. Further, the functioning of many networks and the pathology of many cancers involve complex systems involving more than one network. Thus, the level of ordinary skill in the art needs specialized knowledge of the complex nature of cancer.
(7) The quantity of experimentation needed: Given the fact that, historically, the development of new cancers drugs has been difficult and time consuming, and especially in view of factors 1-6, the quantity of experimentation needed is expected to be undue.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
Claim Rejections - 35 USC § 102
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) 6, 72-76, 81, 83, 95, 97, 98, and 102-107 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025).
Qi et al teach a method of treating pancreatic cancer comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]). Accordingly, the limitations of claims 6, 72, 76, 105, and 106 are satisfied.
Regarding claim 73, the SapC-DOPS and chemotherapeutic regimen are administered together either sequentially or contemporaneously, to act as an antineoplastic agent [reads on within 48 hours] (e.g., paras [0026], [0033]-[0036], [0056], [0066], [0071]-[0085]). Regarding claims 74 and 75, the nanovesicle formulation and chemotherapeutic regimen can be administered intravenously (e.g., paras [0067], [0102]-[0104], claims 5, 6, 25).
Regarding claims 81 and 82, Qi et al teach in each cycle of treatment, administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week, such as three times per week over 45 min ± 15 min, and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (Oxaliplatin 85 mg/m2 IV on day 1 plus irinotecan liposomal, 70 mg/m2 IV infused over 90 min, followed by leucovorin 400 mg/m2 IV infused over 30 min, followed by fluorouracil 2400 mg/m2 IV infused over 46 hours, every 3 weeks) (e.g., paras [0030], [0078], [0084]). The reference further teaches administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (5′fluorouracil 2000 mg/m2 IV over 24 hours on days 1, 8, 15, and 22, leucovorin 200 mg/m2 IV over 30 minutes on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 IV on days 8 and 22, every 42 days) (para [0085]). Regarding claim 83, SapC-DOPS is administered 3 times per week in week 2 of treatment (Table 1).
Regarding claim 95, Qi et al teach that the antineoplastic agent and the nanovesicle formulation are separate (e.g., abstract, paras [0034]-[0035], [006], claims 26-27). Regarding claim 97, SapC-DOPS may ordinarily be administered at a dosage level of 0.5 mg SapC/kg of body weight to 7.0 mg SapC/kg of body weight per dose, such as 0.7 mg SapC/kg of body weight to 4.8 mg SapC/kg of body weight per dose (e.g., para [0060]). Regarding claim 98, treatment increases survival in comparison to control sample (examples, Fig 2). Regarding claims 102-104, the composition comprises or consists of Saposin c. Saposin C has 100% identity with instant SEQ ID NO:1 (e.g., paras [0036], [0027], [0040]-[0041]).
Claim(s) 3, 22, 39, 40, 54-58, 63, 64, 66-70, and 145-149 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
Qi et al teach a method of treating pancreatic cancer comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]).
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Qi et al do not expressly teach “method of reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom”. However, as evidenced by O’Brien, Saposin C was known to be useful in treating neuropathy associated with chemotherapeutics (e.g., Table 1, para [0035]). O’Brien indicates that Saposin C is a domain of 80 amino acids. SEQ ID NO:1 of Qi et al is 80 amino acids in length and has 100% identity with instant SEQ ID NO:1. As evidenced by Hoff et al, oxaliplatin is a chemotherapeutic agent that is known to be associated with a neuropathic symptom, e.g., peripheral neuropathy (e.g., abstract, pp 94-96).
Here, Qi et al teach administering SapC-DOPS and oxaliplatin to treat pancreatic cancer. Although, Qi et al do not expressly teach the claimed effect of reducing the incidence/intensity/duration or delaying onset of a neuropathic symptom associated with a chemotherapeutic agent (e.g., oxaliplatin), the reference performs the same steps of administering SapC-DOPS and oxaliplatin to treat pancreatic cancer in the same patient population [have/at risk for neuropathy-associated with oxaliplatin], using the same dosing amounts of SapC-DOPS (para [0060]). Thus, Qi et al inherently teach the same process of reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom as in the current application. Qi et al therefore anticipates instant claim 3.
Regarding claim 22, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having peripheral neuropathy (abstract, pp 94-96). Regarding claim 39, the nanovesicle formulation in the chemotherapeutic agent can be administered more than once (e.g., paras [0074]-[0085]). Regarding claim 40, the SapC-DOPS nanovesicle does not contain the chemotherapeutic agent (e.g. claim 1). Regarding claims 54-56, the composition comprises or consists of Saposin c. Saposin C (SEQ ID NO:1 of Qi et al) has 100% identity with instant SEQ ID NO:1 (e.g., paras [0036], [0027], [0040]-[0041]). Regarding claims 57-58, Qi et al teach a nanovesicle formulation comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) (e.g., claims 1-3, 11, 12, paras [0082]-[0085]).
Regarding claim 63 and 64, the molar ratio of SapC-DOPS may be 1:1 to 50:1, such as 1:7 to 1:25. The SapC and DOPS may form a nanovesicle (e.g. paras [0005], [0039]- [0042], [0096], [0155], claims 2). Regarding claim 67, SapC-DOPS may ordinarily be administered at a dosage level of 0.5 mg SapC/kg of body weight to 7.0 mg SapC/kg of body weight per dose, such as 0.7 mg SapC/kg of body weight to 4.8 mg SapC/kg of body weight per dose (para. [0060]). Regarding claim 66 and 68, the nanovesicle formulation and chemotherapeutic regimen can be administered intravenously (e.g., paras [0067], [0102]-[0104], claims 5, 6, 25).
Regarding claims 69-70, pharmaceutical compositions may be administered, for example, 30 minutes, hourly or daily; multiple times per day; weekly, multiple times per week; bi-weekly; monthly (e.g., paras [0058], [0084]-[0085]). Each protocol comprises one cycle, and each protocol may be administered to a patient for at least one cycle, such as at least two cycles, such as at least three cycles, such as at least four cycles, such as at least five cycles, such as at least six cycles (paras [0073]-[0085]). Regarding claims 145-146, Qi et al teach that the subject has pancreatic cancer (e.g., abstract, paras [0005]-[0006], [0036], [0039], [0083]-[0085], claim 1). Regarding claims 147-148, Qi et al teach administration of oxaliplatin (e.g., paras. [0054], [0064], [00082]-[00085]). Regarding claim 149, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having acute pain (pp 94-96).
Claim(s) 4, 118, 130, and 133-137 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
Qi et al teach a method of treating pancreatic cancer comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]).
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Qi et al do not expressly teach “reduces the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom side effects”. However, as evidenced by O’Brien, Saposin C was known to be useful in treating neuropathy associated with chemotherapeutics (e.g., Table 1, para [0035]). O’Brien indicates that Saposin C is a domain of 80 amino acids. SEQ ID NO:1 of Qi et al is 80 amino acids in length and has 100% identity with instant SEQ ID NO:1. As evidenced by Hoff et al, oxaliplatin is a chemotherapeutic agent that is known to be associated with a neuropathic symptom, e.g., peripheral neuropathy (e.g., abstract, pp 94-96).
Here, Qi et al teach administering SapC-DOPS and oxaliplatin to treat pancreatic cancer. Although, Qi et al do not expressly teach the claimed effect of reducing the incidence/intensity/duration or delaying onset of a neuropathic symptom associated with a chemotherapeutic agent (e.g., oxaliplatin), the reference performs the same steps of administering SapC-DOPS and oxaliplatin to treat pancreatic cancer in the same patient population [have/at risk for neuropathy-associated with oxaliplatin], using the same dosing amounts of SapC-DOPS (para [0060]). Thus, Qi et al inherently teach the same process and claimed effect of reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom as in the current application. Qi et al therefore anticipates instant claim 4.
Regarding claim 118, Qi teaches that a treatment for pancreatic cancer [reads on gastrointestinal cancer] (abstract, e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Regarding claim 130, the nanovesicle formulation and chemotherapeutic regimen can be administered intravenously (e.g., paras [0067], [0102]-[0104], claims 5, 6, 25). Regarding claims 133-135, the composition comprises or consists of Saposin c. Saposin C (SEQ ID NO:1 of Qi et al) has 100% identity with instant SEQ ID NO:1 (e.g., paras [0036], [0027], [0040]-[0041]). Regarding claims 136-137, Qi et al teach a nanovesicle formulation comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) (e.g., claims 1-3, 11, 12, paras [0082]-[0085]).
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
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) 6, 72-76, 81-93, 95, 97, 98, and 102-106 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025).
Qi et al teach a method of treating pancreatic cancer comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]). Pharmaceutical compositions may be administered, for example, 30 minutes, hourly or daily; multiple times per day; weekly, multiple times per week; bi-weekly; monthly; and the like (para [0058]). Each protocol comprises one cycle, and each protocol may be administered to a patient for at least one cycle, such as at least two cycles, such as at least three cycles, such as at least four cycles, such as at least five cycles, such as at least six cycles. For each protocol, the therapeutic dose of the pharmaceutical compositions described are exemplary and doses may be decided and/or adjusted by the attending physician within the scope of sound medical judgment and experience (paras [0073]-[0085]). Each cycle may comprise the administration of the first and the second pharmaceutical compositions at least one time every week for three weeks with one week off on week four for a number of cycles, such as 6 cycles (para [0074]).
Qi et al do not expressly teach the dosing limitations recited in claims 84-93. The timing of administering the claimed therapeutic agents is considered a result effective variable.
It would be obvious to one of ordinary skill in the art to optimize result effective variables such as timing of SapC-DOPS and chemotherapeutic agent administration. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the timing of administration to achieve optimal activity and therapeutic effectiveness of SapC-DOPS and chemotherapeutic agent in cancer patients. As indicated in Qi et al, it is within the scope of sound medical judgment and experience of an attending physician to adjust the dosing and timing of the claimed therapeutics (e.g., paras [0058]-[0059], [0073]-[0074]). There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, instant claims 84-93 are rendered obvious.
Claims 6, 72-76, 81-93, 95, 97, 98, and 102-106 are rendered obvious in view of the teachings of Qi et al.
Claim(s) 3, 22, 39, 40, 54-58, 63-70, and 145-149 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
The teachings of Qi et al, Hoff et al and O’Brien are set forth above.
Although, Qi et al teach that the molar ratio of SapC-DOPS [SapC:DOPS] may be 1:1 to 50:1, such as 1:7 to 1:25 (e.g., para [0042], reading as 7:1 to 25:1 DOPS:SapC]), the reference does not expressly teach the molar ratio recited in claim 65. The molar ratio of DOPS:SapC is considered a result effective variable.
It would be obvious to one of ordinary skill in the art to optimize result effective variables such molar ratio of DOPS:SapC. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the molar ratio of DOPS:SapC to achieve optimal activity and therapeutic effectiveness of SapC-DOPS in cancer patients. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, instant claim 65 is rendered obvious.
Claims 3, 22, 39, 40, 54-58, 63-70, and 145-149 are rendered obvious in view of the teachings of the cited references.
Claim(s) 4, 118, 130, 133-137, and 142-144 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
The teachings of Qi et al, Hoff et al and O’Brien are set forth above.
Although, Qi et al teach that the molar ratio of SapC-DOPS [SapC:DOPS] may be 1:1 to 50:1, such as 1:7 to 1:25 (e.g., para [0042], reading as 7:1 to 25:1 DOPS:SapC]), the reference does not expressly teach the molar ratio recited in claims 142-144. The molar ratio of DOPS:SapC is considered a result effective variable.
It would be obvious to one of ordinary skill in the art to optimize result effective variables such molar ratio of DOPS:SapC. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the molar ratio of DOPS:SapC to achieve optimal activity and therapeutic effectiveness of SapC-DOPS in cancer patients. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, instant claims 142-144 are rendered obvious.
Claims 4, 118, 130, 133-137, and 142-144 are rendered obvious in view of the teachings of the cited references.
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 3, 4, 6, 22, 39, 40, 54-58, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 10682411 (hereinafter referred to as “the ‘411 patent”), in view of Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
Regarding claims 3 and 4, claims 33 and 41 of the ‘411 patent recite a method of treating cancer comprising a pharmaceutical composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 with zero to four amino acid insertions, substitutions, or deletions; a phosphatidylserine lipid; a buffer at pH 5.0 to 8; trehalose at 1.5 to 9 percent w/v; and water, wherein the polypeptide is at a concentration of 0.4 to 5 mg/ml, and the molar ratio of phosphatidylserine lipid to polypeptide is in the range of 8:1 to 20:1. Claim 36 recites gastrointestinal cancer. SEQ ID No:1 of the ‘411 patent has 100% identity with instant SEQ ID NO:1. Claims 26, 27, 32, 37, and 38 teach SapC-DOPS.
The claims of the ‘411 patent do not expressly teach a combination of a polypeptide of SEQ ID NO:1/ phosphatidylserine lipid and a chemotherapeutic agent (much less associated with neuropathic symptom].
Qi et al teach a method of treating pancreatic cancer [reads on gastrointestinal cancer] comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]).
It would have been obvious to one of ordinary skill in the art to administer SapC-DOPS and oxaliplatin to treat a subject with a gastrointestinal cancer, e.g., pancreatic cancer. The claims of the ‘411 patent teach that SapC-DOPS can be used to treat gastrointestinal cancer. Qi et al teach that SapC-DOPS and oxaliplatin can be used to treat pancreatic cancer, another form of gastrointestinal cancer. As evidenced by Hoff et al, oxaliplatin is an important chemotherapeutic agent for the treatment of various gastrointestinal carcinomas (p. 94). "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). See M.P.E.P. § 2144.06.
The claims of the ‘411 patent and the teachings of Qi et al are silent with regard to “reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom”.
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Qi et al do not expressly teach “reduces the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom side effects”. However, as evidenced by O’Brien, Saposin C was known to be useful in treating neuropathy associated with chemotherapeutics (e.g., Table 1, para [0035]). O’Brien indicates that Saposin C is a domain of 80 amino acids. SEQ ID NO:1 of Qi et al is 80 amino acids in length and has 100% identity with instant SEQ ID NO:1. As evidenced by Hoff et al, oxaliplatin is a chemotherapeutic agent that is known to be associated with a neuropathic symptom, e.g., peripheral neuropathy (e.g., abstract, pp 94-96).
Here, Qi et al teach administering SapC-DOPS and oxaliplatin to treat pancreatic cancer. Although, Qi et al do not expressly teach the claimed effect of reducing the incidence/intensity/duration or delaying onset of a neuropathic symptom associated with a chemotherapeutic agent (e.g., oxaliplatin), the reference performs the same steps of administering SapC-DOPS and oxaliplatin to treat pancreatic cancer in the same patient population [have/at risk for neuropathy-associated with oxaliplatin], using the same dosing amounts of SapC-DOPS (para [0060]). Thus, Qi et al inherently teach the same process and claimed effect of reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom as in the current application. Qi et al therefore anticipates instant claims 3 and 4.
Regarding claim 6, the teachings of the ‘411 claims and Qi et al are set forth above. It would have been obvious to one of ordinary skill in the art to administer SapC-DOPS and oxaliplatin to treat a subject with a gastrointestinal cancer, e.g., pancreatic cancer. The claims of the ‘411 patent teach that SapC-DOPS can be used to treat gastrointestinal cancer. Qi et al teach that SapC-DOPS and oxaliplatin can be used to treat pancreatic cancer, another form of gastrointestinal cancer. As evidenced by Hoff et al, oxaliplatin is an important chemotherapeutic agent for the treatment of various gastrointestinal carcinomas (p. 94). "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). See M.P.E.P. § 2144.06. The skilled artisan would have had a reasonable expectation of success because the references each taught the claimed compounds were useful in treating gastrointestinal cancer. Accordingly, claim 6 is rendered obvious.
Regarding claim 22, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having peripheral neuropathy (abstract, pp 94-96).
Regarding claim 39, the nanovesicle formulation in the chemotherapeutic agent can be administered more than once (e.g., claims 39-40; Qi at paras [0074]-[0085]).
Regarding claim 40, the SapC-DOPS nanovesicle does not contain the chemotherapeutic agent (e.g. Qi at claim 1).
Regarding claims 54-56, 102-104, and 133-135, the claims of the ‘411 patent recite a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 with zero to four amino acid insertions, substitutions, or deletions (e.g. claims 1, 11, 22); two or more amino acid insertions, substitutions, or deletions (e.g., claim 17); comprises SEQ ID NO:1 (claim 8, 18, 29); and consists of SEQ ID NO:1 (claim 9, 19, 30).
Regarding claims 57-58, 105-106, and 136-137, the claims of the ‘411 patent recite a phosphatidylserine lipid that is DOPS (1, 10, 15, 21, 22, 26, 32, 37, 38).
Regarding claims 63, 64, 142 and 143, claims 1, 11, 22 and 37 of the ‘411 patent recite the molar ratio of phosphatidylserine lipid to polypeptide is in the range of 8:1 to 20:1. Claim 38 of the ]411 patent recites the ratio of SapC to DOPS in the composition is in the range of 1:11 to 1:13.
Regarding claim 65 and 144, it would be obvious to one of ordinary skill in the art to optimize result effective variables such molar ratio of DOPS:SapC. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the molar ratio of DOPS:SapC to achieve optimal activity and therapeutic effectiveness of SapC-DOPS in cancer patients. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Regarding claims 66, 68, 74, and 130, claims 37, 38, and 41, of the ‘411 patent teach that the SapC-DOPS is administered intravenously.
Regarding claim 67 and 97, claim 37 of the ‘411 patent discloses a dose ranging from 0.4 mg/kg to 7 mg/kg SapC.
Regarding claim 69, claim 39 of the ‘411 patent recites daily and weekly administrations of SapC.
Regarding claims 70, pharmaceutical compositions may be administered, for example, 30 minutes, hourly or daily; multiple times per day; weekly, multiple times per week; bi-weekly; monthly (e.g., paras [0058], [0084]-[0085]). Each protocol comprises one cycle, and each protocol may be administered to a patient for at least one cycle, such as at least two cycles, such as at least three cycles, such as at least four cycles, such as at least five cycles, such as at least six cycles (Qi at paras [0073]-[0085]).
Regarding claim 72, 147, and 148, Qi et al teach administration of oxaliplatin (platinum-based agent).
Regarding claim 73, the SapC-DOPS and chemotherapeutic regimen are administered together either sequentially or contemporaneously, to act as an antineoplastic agent [reads on within 48 hours] (e.g., Qi at paras [0026], [0033]-[0036], [0056], [0066], [0071]-[0085]).
Regarding claim 75, the chemotherapeutic regimen can be administered intravenously (e.g., Qi at paras [0067], [0102]-[0104], claims 5, 6, 25).
Regarding claims 76, 118, 145, and 146, claim 36 of the ‘411 patent teaches gastrointestinal cancer. Qi et al teach pancreatic cancer.
Regarding claims 81 and 82, Qi et al teach in each cycle of treatment, administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week, such as three times per week over 45 min ± 15 min, and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (Oxaliplatin 85 mg/m2 IV on day 1 plus irinotecan liposomal, 70 mg/m2 IV infused over 90 min, followed by leucovorin 400 mg/m2 IV infused over 30 min, followed by fluorouracil 2400 mg/m2 IV infused over 46 hours, every 3 weeks) (e.g., paras [0030], [0078], [0084]). The reference further teaches administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (5′fluorouracil 2000 mg/m2 IV over 24 hours on days 1, 8, 15, and 22, leucovorin 200 mg/m2 IV over 30 minutes on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 IV on days 8 and 22, every 42 days) (para [0085]).
Regarding claim 83, SapC-DOPS is administered 3 times per week in week 2 of treatment (claim 39 of the ‘411 patent; Qi at Table 1).
Regarding claims 84-93, the timing of administering the claimed therapeutic agents is considered a result effective variable. It would be obvious to one of ordinary skill in the art to optimize result effective variables such as timing of SapC-DOPS and chemotherapeutic agent administration. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the timing of administration to achieve optimal activity and therapeutic effectiveness of SapC-DOPS and chemotherapeutic agent in cancer patients. As indicated in Qi et al, it is within the scope of sound medical judgment and experience of an attending physician to adjust the dosing and timing of the claimed therapeutics (e.g., paras [0058]-[0059], [0073]-[0074]). There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Regarding claim 95, Qi et al teach that the antineoplastic agent and the nanovesicle formulation are separate (e.g., abstract, paras [0034]-[0035], [006], claims 26-27).
Regarding claim 98, treatment increases survival in comparison to control sample (Qi at examples, Fig 2).
Regarding claim 149, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having acute pain (pp 94-96).
Accordingly, claims 3, 4, 6, 22, 39, 40, 54-58, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are rendered obvious by the teachings of the cited references.
Claims 3, 4, 6, 22, 39, 40, 54-58, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12194099 (hereinafter referred to as “the ‘099 patent”), in view of Qi et al (U.S. 2018/0169120- cited in IDS filed 1/15/2025), as evidenced by Hoff et al (Clin Colorectal Cancer 2:93-100 (2012)) and O’Brien (U.S. 20050164948- cited in IDS filed 1/15/2025).
Regarding claims 3 and 4, claims 20 of the ‘099 patent recite a method of treating cancer (gastrointestinal) comprising a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 with zero to four amino acid insertions, substitutions, or deletions; a phosphatidylserine lipid; a buffer at pH 5.0 to 8.0; trehalose; and water, wherein the polypeptide is at a concentration of 0.4 to 5.0 mg/ml, wherein the molar ratio of the phosphatidylserine lipid to the polypeptide is in the range of 8:1 to 20:1, and form of vesicles suspended in the water. Claim 23 recites gastrointestinal cancer. SEQ ID No:1 of the ‘099 patent has 100% identity with instant SEQ ID NO:1. Claims 6-8, 11, and 18 teach SapC-DOPS.
The claims of the ‘099 patent do not expressly teach a combination of a polypeptide of SEQ ID NO:1/ phosphatidylserine lipid and a chemotherapeutic agent (much less associated with neuropathic symptom).
Qi et al teach a method of treating pancreatic cancer [reads on gastrointestinal cancer] comprising administering a first pharmaceutical composition comprising nanovesicles comprising Saposin C and dioleoyl phosphatidylserine (SapC-DOPS) and administering a second pharmaceutical composition comprising an antineoplastic agent [e.g., Folfirinox] (e.g., claims 1-3, 11, 12 paras [0082]-[0085]). Folfirinox is a combination chemotherapy regimen for treatment of advanced pancreatic cancer which includes the administration of four drugs per treatment cycle: folinic acid (leucovorin), a vitamin B derivative, fluorouracil (5-FU), a pyrimidine analog, irinotecan, a topoisomerase inhibitor, and oxaliplatin, a platinum-based antineoplastic agent (para [0054]).
It would have been obvious to one of ordinary skill in the art to administer SapC-DOPS and oxaliplatin to treat a subject with a gastrointestinal cancer, e.g., pancreatic cancer. The claims of the ‘099 patent teach that SapC-DOPS can be used to treat gastrointestinal cancer. Qi et al teach that SapC-DOPS and oxaliplatin can be used to treat pancreatic cancer, another form of gastrointestinal cancer. As evidenced by Hoff et al, oxaliplatin is an important chemotherapeutic agent for the treatment of various gastrointestinal carcinomas (p. 94). "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). See M.P.E.P. § 2144.06.
The claims of the ‘099 patent and the teachings of Qi et al are silent with regard to “reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom”.
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Qi et al do not expressly teach “reduces the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom side effects”. However, as evidenced by O’Brien, Saposin C was known to be useful in treating neuropathy associated with chemotherapeutics (e.g., Table 1, para [0035]). O’Brien indicates that Saposin C is a domain of 80 amino acids. SEQ ID NO:1 of Qi et al is 80 amino acids in length and has 100% identity with instant SEQ ID NO:1. As evidenced by Hoff et al, oxaliplatin is a chemotherapeutic agent that is known to be associated with a neuropathic symptom, e.g., peripheral neuropathy (e.g., abstract, pp 94-96).
Here, Qi et al teach administering SapC-DOPS and oxaliplatin to treat pancreatic cancer. Although, Qi et al do not expressly teach the claimed effect of reducing the incidence/intensity/duration or delaying onset of a neuropathic symptom associated with a chemotherapeutic agent (e.g., oxaliplatin), the reference performs the same steps of administering SapC-DOPS and oxaliplatin to treat pancreatic cancer in the same patient population [have/at risk for neuropathy-associated with oxaliplatin], using the same dosing amounts of SapC-DOPS (para [0060]). Thus, Qi et al inherently teach the same process and claimed effect of reducing the incidence, intensity, and/or duration of a neuropathic symptom, or delaying onset of a neuropathic symptom as in the current application. Qi et al therefore anticipates instant claims 3 and 4.
Regarding claim 6, the teachings of the ‘099 claims and Qi et al are set forth above. It would have been obvious to one of ordinary skill in the art to administer SapC-DOPS and oxaliplatin to treat a subject with a gastrointestinal cancer, e.g., pancreatic cancer. The claims of the ‘099 patent teach that SapC-DOPS can be used to treat gastrointestinal cancer. Qi et al teach that SapC-DOPS and oxaliplatin can be used to treat pancreatic cancer, another form of gastrointestinal cancer. As evidenced by Hoff et al, oxaliplatin is an important chemotherapeutic agent for the treatment of various gastrointestinal carcinomas (p. 94). "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). See M.P.E.P. § 2144.06. The skilled artisan would have had a reasonable expectation of success because the references each taught the claimed compounds were useful in treating gastrointestinal cancer. Accordingly, claim 6 is rendered obvious.
Regarding claim 22, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having peripheral neuropathy (abstract, pp 94-96).
Regarding claim 39, the nanovesicle formulation in the chemotherapeutic agent can be administered more than once (e.g., claims 26-27; Qi at paras [0074]-[0085]).
Regarding claim 40, the SapC-DOPS nanovesicle does not contain the chemotherapeutic agent (e.g. Qi at claim 1).
Regarding claims 54-56, 102-104, and 133-135, the claims of the ‘099 patent recite a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 with zero to four amino acid insertions, substitutions, or deletions (e.g. claims 1); comprises SEQ ID NO:1 (claim 3, 10, 14).
Regarding claims 57-58, 105-106, and 136-137, the claims of the ‘099 patent recite a phosphatidylserine lipid that is DOPS (Claims 6-8, 11, and 18).
Regarding claims 63, 64, 142 and 143, claims 1 and 24 of the ‘099 patent recite the molar ratio of phosphatidylserine lipid to polypeptide is in the range of 8:1 to 20:1. Claims 11 and 25 of the ‘099 patent recites the ratio of SapC to DOPS in the composition is in the range of 1:11 to 1:13.
Regarding claim 65 and 144, it would be obvious to one of ordinary skill in the art to optimize result effective variables such molar ratio of DOPS:SapC. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the molar ratio of DOPS:SapC to achieve optimal activity and therapeutic effectiveness of SapC-DOPS in cancer patients. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Regarding claims 66, 68, 74, and 130, claims 24 and 25 of the ‘099 patent teach that the SapC-DOPS is administered intravenously.
Regarding claim 67 and 97, claim 24 of the ‘099 patent discloses a dose ranging from 0.4 mg/kg to 7 mg/kg SapC.
Regarding claim 69, claim 26 of the ‘099 patent recites daily and weekly administrations of SapC.
Regarding claims 70, pharmaceutical compositions may be administered, for example, 30 minutes, hourly or daily; multiple times per day; weekly, multiple times per week; bi-weekly; monthly (e.g., Qi at paras [0058], [0084]-[0085]). Each protocol comprises one cycle, and each protocol may be administered to a patient for at least one cycle, such as at least two cycles, such as at least three cycles, such as at least four cycles, such as at least five cycles, such as at least six cycles (Qi at paras [0073]-[0085]).
Regarding claim 72, 147, and 148, Qi et al teach administration of oxaliplatin (platinum-based agent).
Regarding claim 73, the SapC-DOPS and chemotherapeutic regimen are administered together either sequentially or contemporaneously, to act as an antineoplastic agent [reads on within 48 hours] (e.g., Qi at paras [0026], [0033]-[0036], [0056], [0066], [0071]-[0085]).
Regarding claim 75, the chemotherapeutic regimen can be administered intravenously (e.g., Qi at paras [0067], [0102]-[0104], claims 5, 6, 25).
Regarding claims 76, 118, 145, and 146, claim 23 of the ‘099 patent teaches gastrointestinal cancer. Qi et al teach pancreatic cancer.
Regarding claims 81 and 82, Qi et al teach in each cycle of treatment, administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week, such as three times per week over 45 min ± 15 min, and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (Oxaliplatin 85 mg/m2 IV on day 1 plus irinotecan liposomal, 70 mg/m2 IV infused over 90 min, followed by leucovorin 400 mg/m2 IV infused over 30 min, followed by fluorouracil 2400 mg/m2 IV infused over 46 hours, every 3 weeks) (e.g., paras [0030], [0078], [0084]). The reference further teaches administering a first pharmaceutical composition comprising SapC-DOPS at a dose of 2.4-5.0 mg/kg at least once per week and sequential or contemporaneous administration of a second pharmaceutical composition comprising modified Folfirinox (5′fluorouracil 2000 mg/m2 IV over 24 hours on days 1, 8, 15, and 22, leucovorin 200 mg/m2 IV over 30 minutes on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m2 IV on days 8 and 22, every 42 days) (para [0085]).
Regarding claim 83, SapC-DOPS is administered 3 times per week in week 2 of treatment (claim 26 of the ‘099 patent; Qi at Table 1).
Regarding claims 84-93, the timing of administering the claimed therapeutic agents is considered a result effective variable. It would be obvious to one of ordinary skill in the art to optimize result effective variables such as timing of SapC-DOPS and chemotherapeutic agent administration. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the timing of administration to achieve optimal activity and therapeutic effectiveness of SapC-DOPS and chemotherapeutic agent in cancer patients. As indicated in Qi et al, it is within the scope of sound medical judgment and experience of an attending physician to adjust the dosing and timing of the claimed therapeutics (e.g., paras [0058]-[0059], [0073]-[0074]). There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Regarding claim 95, Qi et al teach that the antineoplastic agent and the nanovesicle formulation are separate (e.g., abstract, paras [0034]-[0035], [006], claims 26-27).
Regarding claim 98, treatment increases survival in comparison to control sample (Qi at examples, Fig 2).
Regarding claim 149, as evidenced by Hoff et al a patient treated with oxaliplatin has or is at risk of having acute pain (pp 94-96).
Accordingly, claims 3, 4, 6, 22, 39, 40, 54-58, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are rendered obvious by the teachings of the cited references.
Conclusion
No claims allowed.
Claims 1-47, 54-100, 102-110, 118, 130, and 133-149 are pending. Claims 1, 2, 5, 7-21, 23-38, 41-47, 58-62, 71, 77-80, 94, 96, 99, 100, 107-110, and 138-141 are withdrawn.
Claims 3, 4, 6, 22, 39, 40, 54-58, 63-70, 72-76, 81-93, 95, 97, 98, 102-106, 118, 130, 133-137, and 142-149 are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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