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 .
Status of the Claims
Claims 1, 2, 10, 18, 26, 34, 41, 48, 56, 63, and 69-71 are pending.
Domestic Benefit
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Instant application is a U.S. National Stage Entry of PCT/US23/12251, filed 02/03/2023. PCT/US23/12251 claims benefit of U.S. Provisional Application No. 63/306,776, filed 02/04/2022. Therefore, the effective filing date is 02/04/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
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.
Claim 70 is 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 a method of treating multiple myeloma, non-Hodgkin’s lymphoma, or acute myeloid leukemia comprising administering crystalline AMG 397, does not reasonably provide enablement for the treatment of any cancer comprising administering crystalline AMG 397. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397.
Nature of the invention
The nature of the invention is performance of a method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397.
State of the prior art
No single drug has been discovered that is effective in treating the myriad of cancers. See In re Hokum, 226 USPQ 353 (ComrPats 1985).
Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of proliferative diseases, which have in common only some loss of controlled cell growth. 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 almost every part of the body. For example, leukemia is any malignant neoplasm of the blood-forming tissues. Leukemia can arise from many different sources. These include viruses such as EBV, which causes Burkitt's lymphoma, and HTLV -1, linked to certain T cell leukemias. Others are linked to genetic disorders, such as Fanconi's anemia, which is a familial disorder, and Down's syndrome. Other leukemias are caused by exposure to carcinogens such as benzene, and some are actually caused by treatment with other neoplastic agents. Still other leukemias arise from ionizing radiation, and many are idiopathic. Leukemias also differ greatly in the morphology, degree of differentiation, body location (e.g., bone marrow, lymphoid organs, etc.).
Therefore, as shown in the prior art, cancers arising from different sources with different mechanisms of action need different treatment methods.
AMG 397 is taught in the prior art by Tom et al. (Implementing Continuous Manufacturing for the Final Methylation Step in the AMG 397 Process to Deliver Key Quality Attributes, Org. Process Res. Dev., 2021, Vol. 25, pages 486−499) to be useful in the treatment of multiple myeloma (MM) and acute myeloid leukemia (AML), and therefore, Applicant is enabled for the treatment of these cancers comprising administering AMG 397.
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. The invention is directed toward medicine and is therefore physiological in nature. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he 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). The 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”.
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using a method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397. At best, the specification describes an “effective amount”, in paragraph [0073], “an amount effective, when administered to a human or non-human patient, to treat a disease.” No exemplary amounts of an “effective amount” are provided that correspond to the treatment of any specific cancer.
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397.
Similarly, according to the specification, crystalline forms of AMG 397 are capable of treating any cancer in a patient.
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification does not provide any examples for any treatment methods. There is insufficient disclosure to reasonably conclude that the method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397, as recited, would contribute to treatment of any the aforementioned diseases. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which of the crystalline forms of AMG 397 would be capable of treating which cancers. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating a cancer in a patient, comprising administering a crystalline form of AMG 397, is clearly justified.
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 2, 10, 18, 26, 34, 41, 48, 56, and 63 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “characterized by XRPD pattern peaks at 6.2, 7.4, and 15.7 ± 0.2º 2θ”, and the claim also recites “optionally further characterized by XRPD pattern peaks at 11.4, 16.0, 18.0, and 22.1 ± 0.2º 2θ” and “optionally further characterized by XRPD pattern peaks at 10.2, 10.6, 11.9 … and 21.8 ± 0.2º 2θ” which is the narrower statement of the range/limitation. These additional optional peaks are considered a narrower limitation falling within the broad range of XRPD peaks characteristic of “AMG 397 Form 2 hydrate”, since the specification teaches, on pages 21-22, that the AMG 397 Form 2 hydrate inherently comprises all of these optional peaks.
Therefore, claim 2 is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim (the additional XRPD peaks which are inherent in the AMG 397 Form 2 hydrate), and therefore not required, or (b) a required feature of the claims, in which case they should not be listed as optional, but rather required XRPD peaks.
Claims 10, 18, 26, 34, 41, 48, 56, and 63 are rejected for the same reasoning described above.
Claim Rejections - 35 USC § 102 or 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 26, 48, and 69-71 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Tom et al. (cited above), some inventors in common.
Tom et al. teaches the crystallization of AMG 397 and methods of treatment for multiple myeloma (MM) and acute myeloid leukemia (AML). It is taught, on page 494, “the original isolation process started with a heptane/2-methyltetrahydrofuran technical-grade crystallization”. This crystallization of AMG 397 is not characterized in the prior art. However, the method includes heptane and Me-THF, as in the instant Form 5 hydrate of claims 1, 26, and 69-71.
It is also taught, on page 494, that “an aqueous acetic acid/ethanol form-setting recrystallization” is performed over 1 hour at 80 ± 5 °C. This crystallization of AMG 397 is not characterized in the prior art. However, the method includes acetic acid and ethanol, as in the instant Form 8 ethanol solvate of claims 1, 48, and 69-71.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). The lack of recitation of a physical property of a compound in the prior art does not mean that the limitation does not exist, just that the limitation was not discussed.
“[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same...[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977)). See MPEP 2112.
Applicants are reminded that because the prior art reference is silent about the 13C NMR data of the heptane/2-methyltetrahydrofuran technical-grade crystallization, and the X-ray diffraction (XRD) data of both crystallizations, there is no way to compare the prior art with the current application other than to confirm that both compounds share the same chemical structure.
MPEP 2112 states:
"SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY
The claiming of a new use, new function or unknown property, which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)."
In this case, the "unknown property" is the physical data of the 13C NMR and X-ray diffraction (XRD). This is unknown because the prior art reference is silent on this property. MPEP 2112 goes on to state:
"A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection."
Again, the "characteristic" which the prior art is silent on is the 13C NMR and X-ray diffraction (XRPD).
This is not an ordinary inherency situation where it is not explicitly stated what the product actually is. In the reference applied, the reference explicitly teaches exactly what the compound is. In fact, it is the opposite. In a normal inherency situation, the claim is of known structure, and the reference is of unknown structure. Here, the reverse is true, and hence the legal circumstances of inherency-in-the-prior-art do not apply. The only difference is the property of the compound about which the reference happens to be silent.
See for example Ex parte Anderson, 21 USPQ 2d 1241 at 1251, discussion of Rejection E. The claims had “numerical or functional values for certain properties which [the authors of the references] did not measure.” The PTO presented no reasoning as to why the prior art material would have been expected to have those properties. Instead, the decision states, "There is ample precedent for shifting the burden to an applicant to reproduce a prior art product whose final structure or properties are, at least, in part determined by the precise process used in its manufacture." (page 1253).
In another example, certain claims of Ex parte Raychem Corp. 25 USPQ2d 1265 required a linearity ratio of less than 1.2. The decision notes that neither reference discloses any values of the linearity ratio. The PTO presented no reasoning as to what the ratio would be expected to be in the references. The Decision states: "However, this does not end the inquiry since, where the Patent and Trademark Office is not equipped to perform the needed testing, it is reasonable to shift the burden of proof to Raychem to establish that (1) the argued difference exists…."
And indeed, there have been a number of cases in which applicants have pointed to silence of the prior art with regard to this or that property: In re Pearson, 181 USPQ 641; In re Zierden 162 USPQ 102; In re Lemin, 140 USPQ 273; Titanium Metals Corporation of America v. Banner, 227 USPQ 773; In re Benner, 82 USPQ 49. Going further, if silence about properties of prior art compounds could be relied on, then one could not reject over references with no utility (see In re Schoenwald, 22 USPQ2d 1671), since applicants could always insert the utility into the claim as a property.
It is well settled that the PTO can require an applicant to establish that a prior art product does not necessarily possess the characteristics of the claimed product when the prior art and claimed products are identical or substantially identical. An applicant's burden under these circumstances was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977) as follows:
Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product...Whether the rejection is based on 'inherency' under 35 U.S.C. § 102, or 'prima facie obviousness' under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products (footnote omitted).
“[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102. on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same...[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977)). See MPEP 2112. Overcoming the rejection is very straightforward. One simply replicates the prior art procedure. If the XRD and 13C NMR data are different at all in that product, compared to the instant invention, then the rejection is overcome.
Conclusion
Claims 1, 2, 10, 18, 26, 34, 41, 48, 56, 63, and 69-71 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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